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Therapeutics Tracker

69
Total
10
Phase 1
46
Phase 2
13
Phase 3

Therapeutics Information

Last Update : 12/10/2021

Medication Class : Antiviral

Trade Name : Molnupiravir (Lagevrio, formerly known as MK-4482 and EIDD-2801)

Developer Researcher : Ridgeback Biotherapeutics,Merck

Sponsors : Ridgeback Biotherapeutics,Merck

Trial Phase : Phase 3

Details : Background: Molnupiravir (Lagevrio, formerly known as MK-4482 and EIDD-2801) is an oral broad-spectrum antiviral that has shown effectiveness against infections such as influenza, chikungunya, Ebola and equine encephalitis. It has a similar mechanism of action to remdesivir and prevents replication of the virus. In animal models, molnupiravir inhibited the replication of SARS-CoV-2 and MERS in mice, SARS-CoV-2 in Syrian hamsters, and blocks transmission of SARS-CoV-2 in ferrets, according to preclinical papers. Regulatory actions: Australia: Provisional determination status has been granted. Bangladesh: Bangladesh has authorized the use of molnupiravir and is in the process of authorizing generic manufacturers to supply the drug to its citizens.Canada: Merck Canada has initiated a rolling submission.  EU: EMA started a rolling review of molnupiravir as of 25 October and noted that CHMP will provide EU-wide recommendations for early use of the treatment prior to authorization, given increasing case numbers in the region. On 23 November, EMA received an application for marketing authorization of molnupiravir under the name Lagrevrio. The European Commission has listed molnupiravir in its portfolio of ten most promising COVID-19 therapeutics. UK: On 4 November, MHRA approved molnupiravir for use in patients with mild or moderate COVID-19 at high risk of developing severe disease. US: Merck and Ridgeback Bio have applied for an EUA; an advisory committee recommended FDA authorize molnupiravir for emergency use in a 13-10 vote. Trials: A Phase 1 trial of 130 participants who received molnupiravir or placebo has been completed (NCT04392219) as has a Phase 2a safety trial (NCT04405570). A Phase 2/3 trial, the MOVe-IN trial of hospitalized adults (NCT04575584) was terminated, while its outpatient version, MOVe-OUT (NCT04575597) is active, but no longer recruiting. A trial to assess molnupiravir's ability to reduce viral shedding of SARS-CoV-2 (NCT04405739) continues. The Phase 3 MOVe-AHEAD trial, evaluating molnupiravir as post-exposure prophylaxis for individuals living with a person who has tested positive for COVID-19, is currently recruiting (NCT04939428). A generics manufacturer producing and supplying molnupiravir for India, Hetero, is conducting Phase 3 open-label studies on patients with mild and moderate COVID-19.Outcomes: Merck announced results from the Phase 3 MOVe-OUT trial in October 2021, which showed a 50% reduction in hospitalization for non-hospitalized patients with mild or moderate COVID-19 who received the drug. Further results from MOVe-OUT, announced on 26 November, lowered the drug's effectiveness at reducing the risk of hospitalization to 30%. Hetero, a manufacturer that has entered a non-exclusive licensing agreement with Merck regarding molnupiravir, announced results from their own Phase 3 open-label study that showed taking molnupiravir resulted in early clinical improvement and improved median time to clinical improvement compared with standard of care. Early phase results, including from the Phase 1 trial published in Antimicrobial Agents and Chemotherapy, showed molnupiravir was safe and well-tolerated in humans. Results from a Phase 2a trial of a secondary outcome in 202 participants, presented at the CROI meeting, showed a significant reduction in negative SARS-CoV-2 viral culture at 5 days compared with the placebo group.  Status: Merck and Ridgeback Biotherapeutics announced on 15 April that they will proceed with the Phase 3 portion of the MOVe-OUT trial, but would not be continuing with the MOVe-IN trial after an analysis revealed molnupiravir was not effective for hospitalized adults with COVID-19. Pending an EUA, the US government has agreed to purchase 1.7 million 5-day treatment courses of molnupiravir for $1.2 billion. Other countries have also taken steps to procure molnupiravir following positive Phase 3 results, such as Australia, Malaysia, South Korea, and Thailand.

Last Update : 12/10/2021

Medication Class : Monoclonal antibody

Trade Name : Evusheld (tixagevimab and cilgavimab,AZD7442)

Developer Researcher : AstraZeneca,Vanderbilt University Medical Center

Sponsors : AstraZeneca,BARDA

Trial Phase : Phase 3

Details : Background: AstraZeneca is testing Evusheld (tixagevimab and cilgavimab, formerly AZD7442), a combination of two monoclonal antibodies, AZD8895 and AZD1061, to prevent and treat COVID-19. The monoclonal antibodies were discovered by researchers at Vanderbilt University and licensed to AstraZeneca.Regulatory Actions: On 9 December, the FDA issued an EUA for Evusheld as pre-exposure prophylaxis after recent contact with an infected person for individuals 12 years and older who are immunocompromised and/or for whom vaccination is not recommended based on the potential for an allergic reaction. The EUA was issued based on results from the PROVENT trial. EMA started a rolling review of tixagevimab and cilgavimab on 14 October 2021; the European Commission has listed tixagevimab and cilgavimab in its portfolio of ten most promising COVID-19 therapeutics. AstraZeneca Canada has also filed for emergency authorization of tixagevimab and cilgavimab in Canada as a COVID-19 preventative.Trials: A Phase 1 randomized, double-blind, placebo-controlled trial of tixagevimab and cilgavimab for prevention and treatment of COVID-19 in up to 60 participants in the UK (NCT04507256) is no longer recruiting. The company launched two Phase 3 trials with a $486 million cash infusion from BARDA. PROVENT (NCT04625725) is a safety and efficacy trial in up to 5,000 participants; STORM CHASER (NCT04625972), a trial of up to 1,125 participants that will evaluate post-exposure prophylaxis, is currently underway. TACKLE (NCT04723394), an international Phase 3 trial, also is underway. Tixagevimab and cilgavimab are being evaluated in a substudy of the Phase 2/3 ACTIV-2 trial as an intramuscular injection and infusion (NCT04518410), and additionally in the Phase 3 ACTIV-3 trial (NCT04501978).Outcomes: - Phase 1 UK trial: Results from the Phase 1 trial evaluating prevention and treatment of COVID-19, posted as a pre-print in medRxiv, showed tixagevimab and cilgavimab produced serum geometric mean neutralizing titers more than 10 times higher than convalescent sera, and maintained higher serum geometric mean neutralizing titers than convalescent sera for over 9 months. - PROVENT: The combination reduced the incidence of symptomatic COVID-19 by 77% in this trial examining pre-exposure prophylaxis, according to a press release from AstraZeneca and results presented at IDWeek 2021. Six-month results, announced in a press release, indicated the 300-mg group had an 83% reduction in the rate of symptomatic COVID-19.- STORM CHASER: In a June 2021 press release, AstraZeneca announced that tixagevimab and cilgavimab did not meet the primary endpoint in STORM CHASER of post-exposure prevention compared with placebo.- TACKLE: In this Phase 3 trial, tixagevimab and cilgavimab reduced the risk of progression to severe COVID-19 by 67% in patients with mild or moderate disease at high risk of COVID-19 progression, according to a press release from AstraZeneca. Exploratory results from TACKLE, announced by AstraZeneca in November 2021, indicate the risk of progression to severe disease or death was 88% in the 600-mg group compared with placebo.

Last Update : 12/10/2021

Medication Class : Monoclonal antibody

Trade Name : Regkirona (regdanvimab, CT-P59)

Developer Researcher : Celltrion

Sponsors : Celltrion

Trial Phase : Phase 3

Details : Background: Celltrion’s human monoclonal antibody Regkirona (regdanvimab, formerly CT-P59) has been found to neutralize SARS-CoV-2 and several variants. Data from an animal study published in Nature Communications showed reduced clinical symptoms and viral titers in ferrets, hamsters, and rhesus macaques. Trials: A Phase 1 trial of up to 32 participants is underway (NCT04525079). The Korean Ministry of Food and Drug Safety (MFDS) approved a Phase 2/3 trial in up to 1,000 patients in 12 countries in September (NCT04602000), and a Phase 3 trial in up 1,000 participants evaluating the post-exposure prophylaxis of the candidate has been approved by MDFS. A Phase 1 trial has been approved to begin in Australia testing an inhaled version of Regkirona. Outcomes: Topline results from the Phase 3 trial, announced by Celltrion in June 2021, showed Regkirona reduced the progression of COVID-19 to hospitalization or death by 70% overall and 72% for patients at high risk for progressing to severe disease. Positive Phase 3 results also were presented at the European Congress of Clinical Microbiology & Infectious Disease, which reaffirmed the topline results. Interim data from the Phase 1 trial indicated that Regkirona is safe and tolerable without any adverse events. Celltrion announced non-peer-reviewed results from their Phase 2/3 trial which showed treatment with Regkirona (40 kg/mg) resulted in a 54% reduction of progression to severe disease among patients with mild or moderate disease, and a 68% reduction in patients 50 years and older with moderate disease. Regkirona (40 kg/mg) treatment also had a quicker time to recovery (3.4-6.4 days) compared with placebo. The drug also appears to be effective against the B.1.617.2 (Delta) variant, according to a Celltrion press release.Regulatory Actions: - Australia: Provisional approval granted on 6 December.- Brazil: Approved for emergency use on 8 August.- EU: On 12 November, EMA authorized Regkirona as a COVID-19 treatment for adults who are not on supplemental oxygen but are at increased risk of severe disease. Regkirona has been selected as one of five promising COVID-19 therapeutics by the European Commission.- Indonesia: Approved for emergency use 17 July.- South Korea: Approved in September 2021.

Last Update : 12/10/2021

Medication Class : IL-6 receptor agonist

Trade Name : Actemra/RoActemra (tocilizumab)

Developer Researcher : Roche

Sponsors : Various

Trial Phase : Phase 3

Details : Background: Actemra is an IL-6 receptor agonist indicated to treat autoimmune diseases such as rheumatoid arthritis as well as cytokine release syndrome. Regulatory Actions: - WHO: The World Health Organization has recommended IL-6 receptor blockers like Actemra be used in severe and critical COVID-19 cases. - Australia: On 1 December, TGA granted Actemra provisional approval status.- EU: EMA’s CHMP has recommended approval of Actemra (as RoActemra) be expanded to include treatment for patients hospitalized with COVID-19. The European Commission listed Actemra as one of the ten most promising COVID-19 therapeutics in October 2021.- India: A generic version of Actemra manufactured by Hetero Group, under the name Tocira, has been granted an EUA by the DCGI in India. - US: On 24 June, the FDA issued an EUA for use of Actemra in COVID inpatients aged 2 years and older who are on systemic corticosteroids and who require supplemental oxygen, ventilation, or extracorporeal membrane oxygenation (ECMO). Authorization was based on the outcomes of four trials: RECOVERY, EMPACTA, COVACTA, and REMDACTA.  Trials: Actemra is being evaluated in RECOVERY (NCT04381936), COVACTA (NCT04320615), EMPACTA (NCT04372186),  and in REMDACTA in combination with Veklury compared with Veklury alone (NCT04409262). The Hôpitaux de Paris (CORIMUNO-19) is assessing Actemra in a trial for COVID-19 associated pneumonia (NCT04331808) in a Phase 2 trial. Outcomes: Evidence points to Actemra having a beneficial outcome for COVID-19 patients in some, but not all, scenarios. Evidence for benefit: - RECOVERY: 621 patients (31%) who received Actemra died within 28 days compared with 729 patients (35%) who received standard of care, according to data published in The Lancet. - Results from EMPACTA indicate Actemra reduced the need for mechanical ventilation in patients with COVID-19-associated pneumonia. In EMPACTA, 12% of patients receiving Actemra received mechanical ventilation compared with 19.3% of patients in the placebo group (P = .04); however, Actemra did not improve rates of survival, according to data published in the NEJM.- The drug also may improve survival in patients with cytokine release syndrome, according to a study in CHEST. - Results from the University of Michigan published in the journal Clinical Infectious Diseases showed a 45% reduction in hazard of death for COVID-19 patients and improved status compared with patients who did not receive the drug. - In a multicenter cohort study of 4,485 adults with COVID-19 published in JAMA Internal Medicine, researchers found a lower risk of mortality in adults who received Actemra within 2 days of ICU admission compared with patients who did not. - REMAP-CAP: Results published in NEJM showed a hospital mortality rate of 27% for patients taking Actemra compared with 36% among those receiving standard of care.- A retrospective study published in the Journal of Inflammation Research found patients with severe COVID-19 who received Actemra had a significantly lower mortality rate compared with patients who received Actemra plus dexamethasone or dexamethasone alone.- Real-world use of Actemra in Italy showed Actemra with or without corticosteroids improved 14-day disease progression and mortality compared with patients who received standard of care with or without a corticosteroid, according to results published in PLOS One.- Actemra was effective when given at an "early inflammatory stage" of COVID-19 and in moderate doses, but does not appear to impact disease progression, according to a study published in Scientific Reports.Evidence showing mixed results: - Researchers on behalf of the Niguarda COVID-19 Working Group released a comparative analysis in the Journal of Infection that noted Actemra is potentially effective but recommended caution when using the drug. - A randomized, double-blind, placebo-controlled trial published in the NEJM by researchers at Massachusetts General Hospital found Actemra was not effective in reducing the need for intubation, disease progression, or death but left open the opportunity that the drug did carry some benefit due to wide confidence intervals in comparisons of efficacy. - CORIMUNO-19: Fewer patients hospitalized with COVID-19 and moderate-to-severe pneumonia taking Actemra who required noninvasive ventilation, intubation, or died at 14 days compared with placebo, but Actemra did not meet the primary outcome of reducing clinical progression scores by 5 days after starting treatment. A follow-up to the trial, published in JAMA Internal Medicine, found that Actemra may improve the need for invasive or non-invasive ventilation and mortality rate at 14 days but not mortality at 28 days.- REMDACTA: In this trial, results announced by press release showed Actemra plus Veklury did not improve time to discharge for patients with severe COVID-19 and pneumonia compared with Veklury alone.Evidence showing no benefit: - In the COVID-BioB Study, patients who received Actemra instead of standard of care had improved clinical outcomes (69% vs. 61%; P = .61) and reduced mortality (15% vs. 33%; P = .15), but neither result was statistically significant. - Results posted in medRxiv by researchers at the University of North Carolina, Chapel Hill, showed that of 11 patients with severe COVID-19 requiring ventilation, Actemra reduced C-reactive protein levels but did not result in significant improvement in temperature and oxygen requirements. - An Italian study sponsored by the Italian Medicine Agency (AIFA) was stopped after Actemra failed to perform better than standard of care in reducing respiratory symptoms, intensive care visits and mortality. - In the COVACTA study, there was no significant clinical improvement seen in hospitalized patients with COVID-19 and severe pneumonia taking Actemra compared with placebo at 28 days with regard to clinical status or mortality, according to results published in NEJM. Status: NHS advises clinicians may use Actemra for certain COVID-19 inpatients being treated with corticosteroids who have had respiratory support initiated within the previous 24 hours, based on the RECOVERY trial. Guidelines from the Infectious Diseases Society of America recommend the use of Actemra with dexamethasone in certain COVID-19 inpatients who are experiencing a rapid decline.

Last Update : 12/10/2021

Medication Class : Monoclonal antibody

Trade Name : Amubarvimab and romlusevimab (formerly BRII-196 and BRII-198)

Developer Researcher : Brii Biosciences Limited

Sponsors : NIAID

Trial Phase : Phase 3

Details : Background: Brii Biosciences Limited is testing two of their monoclonal antibody therapies against COVID-19: amubarvimab and romlusevimab (formerly BRII-196 and BRII-198). Regulatory Actions: The therapy has been approved for use in China for mild and moderate COVID-19 at high risk of progression to severe disease. On 9 October, Brii Biosciences began submitting data to the FDA for an EUA for outpatients with COVID-19, based on results from the ACTIV-2 study.Trials: The company has evaluated amubarvimab (NCT04479631) and romlusevimab (NCT04479644) in small Phase 1 trials for safety, tolerability, and pharmacokinetics. Those trials are active, but not recruiting. The monoclonal antibodies are also being evaluated in the Phase 3 ACTIV-2 (NCT04518410) and ACTIV-3 trials (NCT04501978), which are sponsored by NIAID.Outcomes: Results of an interim analysis of data from 837 non-hospitalized participants in the ACTIV-2 trial, announced through a press release on 24 August, showed amubarvimab/romlusevimab significantly reduced hospitalization and mortality by 78% compared with placebo (relative risk, 0.22; 95% CI, 0.05-0.86; P < .00001). On 3 October, Brii Biosciences announced results for the ACTIV-2 trial that they presented at IDWeek 2021, which showed amubarvimab/romlusevimab reduced hospitalization or mortality by 78% in non-hospitalized patients with COVID-19.Status: On 03 March, NIH announced it was closing enrollment of the ACTIV-3 sub-study of amubarvimab/romlusevimab due to futility. Amubarvimab and romlusevimab advanced to the Phase 3 portion of the ACTIV-2 study as of 29 April, according to a press release from Brii Biosciences.

Last Update : 12/10/2021

Medication Class : Anticoagulant

Trade Name : Heparin (UF and LMW)

Developer Researcher : NHLBI

Sponsors : Operation Warp Speed,University of Pittsburgh

Trial Phase : Phase 2/3/4

Details : Background: Heparin is being evaluated in several collaborative high-profile trials to determine its efficacy as a therapeutic for COVID-19. Trials: In the Phase 3 ACTIV-4a inpatient protocol, NIH researchers seek to evaluate if heparin has an effect on reducing clotting events that develop as a result of COVID-19. Patients receive various doses of unfractionated or low-molecular-weight heparin (NCT04505774). Another Phase 2/3 trial, ATTACC, is evaluating heparin in patients hospitalized with COVID-19 in Canada (NCT04372589). Heparin is also a treatment arm of REMAP-CAP, a multifactorial, adaptive platform Phase 4 trial evaluating patients with community-acquired pneumonia, which has a subplatform specific to COVID-19 (NCT02735707). Internationally, researchers are evaluating anticoagulation as a COVID-19 treatment compared with standard of care in the RAPID trial (NCT04362085) (NCT04444700). A Phase 3 trial, HEP-COVID, sponsored by Northwell Health evaluating full-dose heparin as a prophylactic and high-dose heparin as a treatment for patients with high-risk COVID-19 has been completed (NCT04401293).Outcomes: - On 28 January, non-peer-reviewed results were posted to the ATTACC website in a slideshow presentation of the primary outcome for the ACTIV-4a, ATTACC and REMAP-CAP trials, which was number of organ support-free days up to day 21. In the results, heparin with moderate state, low D-dimer had a median proportional odds ratio of 1.57 (95% Crl, 1.14 - 2.19) and moderate state, high D-dimer heparin had a proportional odds ratio of 1.53 (1.09 - 2.17), indicating superiority over usual prophylactic dosing.- Critically ill COVID-19: Patients hospitalized and critically ill with COVID-19 in the REMAP-CAP, ACTIV-4a, and ATTACC trials who received heparin were not more likely to survive discharge or have more days free of supporting care compared with patients who did not receive heparin, according to a study published in NEJM.- Non-critically ill COVID-19: Patients in the REMAP-CAP, ACTIV-4a, and ATTACC trials who were hospitalized for COVID-19 but not critically ill who received heparin were more likely to survive until being discharged or not need the use of supporting care compared with those who did not receive heparin, according to a study published in NEJM. - In a paper published in the journal Circulation, researchers cautioned against using therapeutic doses of anticoagulation in patients with severe COVID-19, as it may result in heparin-induced thrombocytopenia. - Among patients at Brigham and Women's hospital with and without COVID-19 who received weight‐based nursing‐nomogram titrated unfractionated heparin, the COVID-positive group had fewer therapeutic activated partial thromboplastin times and more major bleeding events 10.3% (95% CI, 5.7%‐17.9%) compared with patients who were COVID-19 negative 3.1% (95% CI, 1.6%‐5.9%), according to a paper published in Research and Practice in Thrombosis and Haemostasis.- RAPID: Heparin given therapeutically did not significantly reduce the likelihood of a composite outcome of invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission, there was a reduction in the likelihood of mortality at 28 days, according to a paper posted to medRxiv.- A retrospective study showed low-molecular-weight heparin reduces the risk of mortality for patients with COVID-19, according to an abstract presented at the European Congress of Clinical Microbiology & Infectious Diseases. Another retrospective study of hospitalized patients in Austria, published in Cardiovascular Research, showed low-molecular-weight heparin improved survival and reduced the number of days a patient tested positive for the virus.- HEP-COVID: A therapeutic dose of low-dose heparin applied prophylactically reduced the risk of blood clots among patients hospitalized with COVID-19 with "very elevated D-dimer levels" compared with standard of care for thromboprophylaxis, according to data published in JAMA Internal Medicine.Status: On 22 December, the ACTIV-4 trial paused enrollment for patients with COVID-19 who are critically ill and in the intensive care unit after it was found that anticoagulation drugs do not reduce the need for organ support; other participants, including those with moderate cases of COVID-19, are still being enrolled.

Last Update : 12/10/2021

Medication Class : Lipid-lowering agent

Trade Name : Vascepa (icosapent ethyl)

Developer Researcher : Amarin Corporation

Sponsors : Amarin Pharma Inc.,Kaiser Permanente,Estudios Clínicos Latino América,Canadian Medical and Surgical Knowledge Translation Research Group

Trial Phase : Phase 2/3/4

Details : Background: Vascepa (icosapent ethyl) is a lipid-lowering agent being evaluated by Amarin Corporation as a therapeutic for patients with COVID-19. It is approved by the US FDA to treat severe hypertriglyceridemia and reduce the risk for cardiovascular events.Trials: Amarin has launched a Phase 2 trial evaluating how Vascepa impacts biomarkers in patients with COVID-19 (NCT04412018), the Phase 3 PREPARE-IT trial to evaluate Vascepa as a COVID-19 prophylactic for healthcare providers (NCT04460651) and the Phase 4 MITIGATE trial to reduce the rate of upper airway infection for patients with COVID-19 as well as "influenza, and other known viral respiratory pathogens" (NCT04505098).Outcomes: Results from the Phase 2 trial presented at the National Lipid Association Virtual Scientific Sessions in December 2020 showed Vascepa reduced high-sensitivity C-reactive protein and patient symptoms at 14 days compared with usual care. Topline results presented at the 2021 European Society of Cardiology Congress showed Vascepa did not meet the primary endpoint of the PREPARE-IT trial, with a COVID-19 case rate of 7.9% in the Vascepa group compared with 7.1% among patients on placebo, according to reporting from Medscape. An abstract from the American Heart Association’s Scientific Sessions 2021 indicated that Vascepa did not significantly reduce hospitalization or mortality.

Last Update : 12/10/2021

Medication Class : Antiviral

Trade Name : Paxlovid (PF-07321332) + ritonavir

Developer Researcher : Pfizer

Sponsors : Pfizer

Trial Phase : Phase 2/3

Details : Background: Pfizer is developing an antiviral therapeutic combination for COVID-19 called Paxlovid (PF-07321332), which is being administered with the HIV antiviral ritonavir. It is a protease inhibitor that blocks an enzyme in SARS-CoV-2 and stops the virus from replicating. The therapeutic has shown promise as an antiviral against SARS-CoV-2 in vitro clinical testing, according to the company.Trial: A Phase 1 double-blind trial of up to 60 participants was completed (NCT04756531). Two Phase 2/3 trials evaluating non-hospitalized patients with COVID-19 at low risk (EPIC-SR) (NCT05011513) and high risk (EPIC-HR) (NCT04960202) are underway. The Phase 2/3 EPIC-PEP trial is investigating Paxlovid and ritonavir's effect as post-exposure prophylaxis for individuals living in the same household as someone who was diagnosed with COVID-19 (NCT05047601). A trial of Paxlovid is reportedly planned in Russia, according to reporting from Reuters.Outcomes: In an interim analysis of 1,219 participants in the Phase 2/3 EPIC-HR trial, announced by Pfizer through a press release on 5 November, patients who received Paxlovid and ritonavir had a 89% reduction in hospitalization or death compared with placebo if the patient was treated within 3 days of developing symptoms (0.8% vs. 7.0%; P < .0001)Regulatory Actions: Pfizer has submitted data from the Phase 2/3 EPIC-HR trial in the US FDA in support of an EUA; the US government has agreed to purchase 10 million treatment courses of Paxlovid if the drug is authorized. In Australia, TGA has granted Paxlovid and ritonavir provisional determination status. EMA started a rolling review of Paxlovid on 19 November. The European Commission has listed Paxlovid in its portfolio of ten most promising COVID-19 therapeutics. An agreement between Pfizer and the UN-backed Medicines Patent Pool would allow generic manufacturers to supply Paxlovid in approximately 95 countries, according to a press release.

Last Update : 12/10/2021

Medication Class : Monoclonal antibody

Trade Name : Sotrovimab, also known as Xevudy (VIR-7831, GSK4182136)

Developer Researcher : GSK, Vir Biotechnology

Sponsors : GlaxoSmithKline

Trial Phase : Phase 2/3

Details : Background: Vir Biotechnology, Inc. and GlaxoSmithKline are evaluating their monoclonal antibody sotrovimab (also known as VIR-7831, formerly GSK4182136) to treat COVID-19. Sotrovimab has shown the ability to neutralize SARS-CoV-2 in vitro, according to the companies.Regulatory Actions:- Australia: Provisionally approved by TGA on 20 August; called Xevudy in Australia.- Bahrain: Approved for emergency use on 1 July.- Canada: Approved for emergency use on 30 July.- EU: EMA concluded on 21 May that sotrovimab can be used for adolescents 12 years and older and adults with mild or moderate COVID-19 not on supplemental oxygen or who have a risk of progressing to severe COVID-19. Sotrovimab's market authorization application has been received by EMA. The EC has twice named sotrovimab as a promising therapeutic – once in June 2021 and again in October 2021.- Italy: On 13 July, Italy temporarily approved the distribution of sotrovimab in the country.- Japan: Approved for patients with mild or moderate COVID-19 in September 2021.- UK: Approved by MHRA on 2 December.- US: On 26 May, FDA authorized sotrovimab for emergency use as a treatment for mild and moderate COVID-19 in adolescents 12 years and older and adults based on data from the COMET-ICE trial. Trials: Sotrovimab is being evaluated in a sub-study of ACTIV-3 in patients hospitalized with COVID-19. The Phase 2/3 COMET-ICE trial, evaluating sotrovimab against placebo in up to 1,360 participants who will be followed for up to 24 weeks (NCT04545060). Another monoclonal antibody developed by Vir and GSK, VIR-7832, is being evaluated in the Phase 1b/2a AGILE study as a treatment for patients with mild-to-moderate COVID-19; in AGILE, VIR-7832 will be tested for safety and tolerability in the Phase 1b portion of the study and then compared with sotrovimab and placebo in the Phase 2a portion of the study (NCT04746183). Sotrovimab is also being evaluated in BLAZE-4 (NCT04634409), a trial of patients with mild or moderate COVID-19 receiving bamlanivimab alone, together with etesevimab (JS016), or placebo, which was expanded to also include sotrovimab.Outcomes: On 29 March, Lilly, Vir and GSK announced topline results from the BLAZE-4 trial, which showed patients who received bamlanivimab (700 mg) together with sotrovimab (500 mg) had a 70% reduction in viral load at 7 days compared with a placebo group. An interim data analysis of 583 patients in the COMET-ICE trial, published in NEJM, showed 3 patients (1%) who received sotrovimab progressed to severe disease that led to being hospitalized or dying compared with 21 patients (7%) who received a placebo, with a relative risk reduction of 85% for patients in the sotrovimab group (P = .002). Status: The National Institutes of Health updated their treatment guidelines for COVID-19 in June 2021 to recommend sotrovimab for patients with mild or moderate COVID-19 not currently hospitalized but at risk for progressing to severe disease. The US government has agreed to purchase $1 billion worth of sotrovimab. The EU has reached an agreement with GSK and Vir to supply the EU with up to 220,000 doses of sotrovimab pending an emergency authorization.

Last Update : 12/10/2021

Medication Class : Monoclonal antibodies

Trade Name : Bamlanivimab + etesevimab

Developer Researcher : Lilly,Junshi Biosciences

Sponsors : Lilly,Junshi Biosciences,Operation Warp Speed

Trial Phase : Phase 2/3

Details : Background: Bamlanivimab (formerly LY-CoV555) and etesevimab (formerly JS016 and LY-CoV016) are two monoclonal antibody treatments developed for COVID-19. Bamlanivimab is developed by Eli Lilly and Company, while etesevimab is developed by Junshi Biosciences. They are being evaluated in combination in several high-profile clinical trials. Regulatory Actions: - EU: On 5 March, EMA issued advice that bamlanivimab alone and together with etesevimab could be used as a treatment for at risk of developing severe COVID-19 not on supplemental oxygen. EMA also began a rolling review of bamlanivimab and etesevimab on 11 March, but Eli Lilly ended the rolling review on 2 November due to lack of demand from European Union member states. - India: On 1 June, bamlanivimab and etesevimab were approved for emergency use together in India for patients with mild or moderate COVID-19.- US: On 9 February, FDA issued an EUA for bamlanivimab and etesevimab together as one treatment for adults and adolescents 12 years or older at risk for developing severe COVID-19. The EUA was issued based on evidence from the BLAZE-1 and BLAZE-4 trials. FDA had previously issued an EUA on 9 November for bamlanivimab alone as an injection (700 mg/20 mL) in adults and adolescents 12 years and older with mild or moderate COVID-19 at high risk for progressing to severe COVID-19 and/or hospitalization based on results from the BLAZE-1 trial. FDA revised its fact sheets for healthcare providers on bamlanivimab alone and bamlanivimab with etesevimab to account for new information on the effectiveness of the therapeutic for SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.427 (Epsilon), and B.1.526 (Iota). In April, Lilly announced that it asked the FDA to revoke the EUA for bamlanivimab alone to complete the transition to supply only bamlanivimab/etesevimab to treat COVID-19 in the US, in cooperation with the FDA, which the FDA did the same day. On 27 August, FDA modified the EUA for bamlanivimab and etesevimab, restricting its use to US states and territories where the combined frequency of SARS-CoV-2 variants resistant to the monoclonal antibody treatments comprise less than or equal to 5%. Distribution of bamlanivimab and etesevimab to US states and territories that meet this criterion have resumed; the distribution of bamlanivimab and etesevimab was previously paused in the US on 25 June 2021 due to the emergence of P.1 (Gamma) and B.1.351 (Beta) variants. On 16 September, FDA revised the EUA to include bamlanivimab and etesevimab as prophylaxis for COVID-19 in individuals 12 years and older. FDA expanded the EUA on 3 December to include all younger patients, including newborns.Trials: Key trials evaluating bamlanivimab and etesevimab include:- BLAZE-1 (NCT04427501), a Phase 2 study of 800 patients with mild to moderate COVID-19 receiving bamlanivimab alone or in combination with etesevimab.- BLAZE-2 (NCT04497987), a Phase 3 study of long-term care residents with COVID-19 being conducted with NIAID.- BLAZE-4 (NCT04634409), a trial of patients with mild or moderate COVID-19 receiving bamlanivimab alone, together with etesevimab (JS016), or placebo. BLAZE-4 has been expanded to also include VIR-7831 from Vir Biotechnology/GSK.- ACTIV-2: ACTIV-2 (NCT04518410), a trial of patients with symptoms of COVID-19 who have not been hospitalized.- ACTIV-3 (NCT04501978), a trial of patients receiving bamlanivimab in combination with Veklury for hospitalized patients.- A Lilly executive told Reuters that bamlanivimab and etesevimab are being evaluated in a trial against the B.1.351 variant of SARS-CoV-2 originating in South Africa.- A Phase 1 trial (NCT04411628) of 24 patients hospitalized with COVID-19 who received bamlanivimab or placebo was completed. Outcomes: - BLAZE-1: Data from 1,035 patients in BLAZE-1 showed a 70% reduction in COVID-19 related hospitalizations and deaths among patients taking bamlanivimab and etesevimab compared with placebo (P < .001), according to a study published in NEJM. - BLAZE-4: In a press release, Lilly shared initial results that showed lower doses of both bamlanivimab and etesevimab had similar viral load and pharmacodynamic/pharmacokinetic data compared with higher doses of the combination of drugs.Status: In updated treatment guidelines on 8 April, NIH recommended the use of bamlanivimab/etesevimab for "outpatients with mild to moderate COVID-19 who are at high risk of clinical progression" but recommended against bamlanivimab monotherapy, citing evidence of reduced effectiveness against new SARS-CoV-2 variants. On 25 June, The distribution of bamlanivimab and etesevimab was paused in the US due to the emergence of P.1 and B.1.351 variants. 

Last Update : 12/10/2021

Medication Class : Monoclonal antibody

Trade Name : Lenzilumab

Developer Researcher : Humanigen,Catalent

Sponsors : NIAID

Trial Phase : Phase 2/3

Details : Background: Lenzilumab has been shown to have a protective effect against cytokine release syndrome associated with CAR-T therapy, therefore could aid cytokine-mediated immunopathology of COVID-19 lung injury and ARDS. Regulatory Actions: On 2 April, FDA authorized the use of lenzilumab in COVID-19 patients under an eIND application. FDA declined Humanigen's request for an EUA for the use of lenzilumab in hospitalized COVID-19 patients and noted the company could submit additional data as it becomes available. On 14 June, Humanigen submitted a rolling review request in the UK. The European Commission has listed lenzilumab in its portfolio of the ten most promising COVID-19 therapeutics.Trials: The multicenter, Phase 3, randomized, double-blinded, controlled, clinical LIVE-AIR trial with lenzilumab for the prevention of ARDS in patients with pneumonia associated with COVID-19 (NCT04351152) is underway in the US. Lenzilumab also is being evaluated in NIAID's Big Effect trial in combination with Veklury compared with Veklury plus placebo (NCT04583956). Outcomes: Early results from the first 12 patients who received lenzilumab at Mayo Clinic locations showed 11 of 12 (92%) had clinical improvement, with a median discharge time of 5 days. Oxygenation also was improved in patients taking lenzilumab. Further results published in Mayo Clinic Proceedings showed lenzilumab was associated with an 80% reduction in risk of mechanical ventilation and mortality. Results from the LIVE-AIR trial, published in The Lancet Respiratory Medicine, showed the therapeutic improved survival without the need for mechanical ventilation by 54% compared with a placebo group. Results from a Phase 3 trial presented at IDWeek 2021 showed lenzilumab significantly improved survival for patients receiving lenzilumab without the need for mechanical ventilation.Status: Humanigen has entered into a Cooperative Research and Development Agreement (CRADA) with the US Department of Defense as part of OWS, and in advance of a potential EUA, according to a 06 November press release. The Big Effect Trial has been advanced to a Phase 2/3 trial as of 30 July. 

Last Update : 12/10/2021

Medication Class : Immunoglobulin

Trade Name : Convalescent plasma

Developer Researcher : Various

Sponsors : Various

Trial Phase : Phase 1/2

Details : Background: Convalescent plasma has been studied as passive immunotherapy in other coronaviruses such as MERS and in SARS-CoV-2. Immunome is developing a biosynthetic convalescent plasma (IMM-BCP-01) with funding from the Department of Defense.Regulatory Actions: FDA first issued an EUA for the use of convalescent plasma for patients hospitalized with suspected or laboratory-confirmed COVID-19 on 23 August 2020. The EUA decision was based on convalescent plasma’s history of effectiveness in other coronaviruses, efficacy and safety data in animal models, published studies on safety and efficacy in humans, and data from the National Expanded Access Treatment Protocol (EAP) led by the Mayo Clinic. In a fact sheet issued to providers, FDA emphasized that convalescent plasma is not standard of care for COVID-19, and changes should not be made to current clinical trials of convalescent plasma based on the EUA. FDA reaffirmed their decision to issue an EUA for convalescent plasma in September, saying it "met the criteria for issuance of an EUA" but clarified that convalescent plasma does not meet "the same evidentiary standard as required for approval or licensure of a drug or biological product." In a Letter of Authorization released on 4 February, FDA issued a revised EUA that stated only convalescent plasma with high titers of antibodies should be used for early treatment of patients hospitalized for COVID-19 based on new data from randomized controlled trials. FDA previously had allowed the use of convalescent plasma from recovered cases of COVID-19 for patients with serious or immediately life-threatening COVID-19 infections under an investigational new drug (eIND) application. Guidance for industry released by the FDA on 15 January clarified that convalescent plasma should not be collected from patients who received treatment or vaccine for COVID-19 unless otherwise indicated in the guidance.The World Health Organization (WHO) has strongly advised against using convalescent plasma for patients with mild illness, and recommends against using the therapeutic in patients with severe disease or are critically ill. Trials: Convalescent plasma is being evaluated against placebos, other treatments, and standard of care in a number of high-profile trials: NYU Langone Health and Albert Einstein (active, not recruiting: NCT04364737).Cedars-Sinai Medical Center (recruiting: NCT04353206).Johns Hopkins University (active, not recruiting: NCT04323800, NCT04377672; recruiting: NCT04373460).Baylor Research Institute (not recruiting: NCT04333251).Stanford University, C3PO trial (completed: NCT04355767).A treatment arm of the RECOVERY trial.A treatment arm of the REMAP-CAP study. Outcomes: - Mayo Clinic: In a safety update published in Mayo Clinic Proceedings, mortality improved from 12% as reported in the pre-print to 8.6%. Further evidence from Mayo Clinic researchers posted in the pre-print server medRxiv found convalescent plasma reduced mortality by about 57% compared with standard of care in patients hospitalized with COVID-19. Results from the Covid-19 Convalescent Plasma EAP, published in NEJM, showed convalescent plasma with higher antibody levels was associated with lower mortality (22.3%) within 30 days than convalescent plasma with medium antibody levels (27.4%) or lower antibody levels (29.6%). A drop in use of convalescent plasma was associated with an increase in mortality that was not explained by hospital admission rates, patient age, and SARS-CoV-2 variants, according to a recent paper from Mayo Clinic researchers published in eLife.- US COVID-19 Plasma EAP Consortium: A large study posted in the pre-print server medRxiv from the US Expanded Access Program (EAP) COVID-19 Plasma Consortium of more than 35,000 patients with COVID-19 in an expanded access program found patients had a 7-day mortality rate of 8.7% if they received convalescent plasma 3 days after diagnosis and 11.9% if they received convalescent plasma 4 days after diagnosis; however, the efficacy of the treatment has been called into question due to lack of a placebo group. - Houston Methodist: In the first peer-reviewed study of convalescent plasma, 19 of 25 patients (76%) with severe COVID-19 who received convalescent plasma had clinical improvement. Results from a group of 351 patients from Houston Methodist hospitalized with COVID-19 and given convalescent plasma indicate the “optimal window” for administration was within 44 hours, according to a paper of 60-day follow-up data posted to medRxiv. - PLACID Trial: Results from a randomized controlled Phase 2 trial in India published in The BMJ found patients with COVID-19 who received convalescent plasms did not have significantly different rates of disease progression or mortality compared with patients who received placebo. - Fundación INFANT–COVID-19 Group: In research published in NEJM, 160 older adults with mild COVID-19 symptoms were randomized to receive high-titer convalescent plasma or placebo; severe respiratory disease developed in 16% of patients who received the treatment compared with 31% of patients who received placebo. - REMAP-CAP: Results published in JAMA indicate that patients critically ill with COVID-19 do not have more organ support-free days when receiving high-titer convalescent plasma compared with patients who did not receive convalescent plasma.- PlasmAr Study Group: A randomized controlled trial published in NEJM of 333 patients in Argentina found no significant differences in clinical outcomes or mortality between patients in the convalescent plasma group and the placebo group.- RECOVERY: High-titer convalescent plasma was not associated with improvement in 28-day mortality, proportion of patients discharged from the hospital, and progression to invasive mechanical ventilation or death compared usual care, according to results published in The Lancet.- SIREN-C3PO: Convalescent plasma did not prevent disease progression among high-risk patients with COVID-19 when administered within 1 week of symptoms in a hospital setting, according to a study published in NEJM.Status: On 3 March, NIH announced it was halting its C3PO trial after an independent data monitoring board found convalescent plasma did not significantly benefit patients with mild or moderate COVID-19. 

Last Update : 11/19/2021

Medication Class : Antibody cocktail

Trade Name : Casirivimab/imdevimab (REGEN-COV, REGN-COV2)

Developer Researcher : Regeneron,Cipla,Roche

Sponsors : Regeneron

Trial Phase : Phase 2/3

Details : Background: Casirivimab and imdevimab, also known as REGEN-COV (formerly known as REGN-COV2; called Ronapreve in Europe), are monoclonal antibodies used as a cocktail to target the spike protein of SARS-CoV-2. In India, the combination of casirivimab and imdevimab is being distributed by Cipla. In August 2020, Regeneron and Roche announced a collaboration on casirivimab and imdevimab, agreeing that Regeneron would market the combination in the US, while Roche would do so in the rest of the world. Regulatory Actions: - WHO: Casirivimab and imdevimab are on the list of the World Health Organization's recommended treatments for COVID-19.- Australia: Provisional approval granted by TGA on 18 October; known as Ronapreve in Australia.- Brazil: Anvisa authorized casirivimab and imdevimab on 20 April for use in mild and moderate COVID-19 cases.- Bahrain: Approved for emergency use on 16 June.- Canada: Interim Order authorization granted on 9 June to treat patients with mild or moderate COVID-19.- EU: On 11 November, EMA authorized casirivimab and imdevimab under the name Ronapreve for individuals 12 years and old who don't require supplemental oxygen but are at high risk of progressing to severe disease. The European Commission has included casirivimab/imdevimab on its list of promising therapeutics twice – once in June 2021 and again in October 2021. - India: CDSCO approved casirivimab and imdevimab on 5 May, according to Cipla.- Japan: Fully approved for use in the treatment of mild or moderate COVID-19 cases on 20 July.- Singapore: HSA granted interim authorization of casirivimab and imdevimab on 21 September.- Sri Lanka: Approved in June 2021.- UK: Approved for use as prevention or treatment for COVID-19 on 20 August by MHRA.- US: FDA issued an EUA for the combination of casirivimab and imdevimab to treat mild to moderate COVID-19 in adults or pediatric patients aged 12 years or older, based on safety and efficacy data in a Regeneron-sponsored trial evaluating ambulatory adult patients with COVID-19 (NCT04425629). On 18 March, FDA revised its fact sheets for healthcare providers on casirivimab and imdevimab to account for new information on its efficacy against a number of SARS-CoV-2 variants. A lower dose of casirivimab/imdevimab (1,200 mg) was authorized by FDA on 4 June, according to Regeneron. The EUA was updated on 30 July to extend the use of casirivimab/imdevimab as post-exposure prophylaxis for some individuals 12 years and older who tested positive for COVID-19 and are at greater risk for progression to severe disease; the authorization was issued based on Phase 3 results from a Phase 1/2/3 trial of ambulatory patients with COVID-19 sponsored by Regeneron and topline results from a Phase 3 NIH trial evaluating casirivimab/imdevimab as post-exposure prophylaxis. The FDA has also accepted a BLA for review of casirivimab/imdevimab as a COVID-19 and prophylaxis for some individuals, according to a press release from Roche.Trials: Regeneron launched has launched several high-profile trials evaluating casirivimab/imdevimab:- A Phase 1/2/3 trial in hospitalized patients with COVID-19 (NCT04426695) - A Phase 1/2/3 trial of ambulatory adult patients with COVID-19 (NCT04425629), which established safety and is proceeding to Phase 2/3 portion to evaluate whether the antibody cocktail can effectively treat hospitalized and non-hospitalized COVID-19 patients. - A Phase 1 trial involving repeated subcutaneous dosing of casirivimab/imdevimab in healthy volunteers (NCT04519437). - A Phase 3 trial in collaboration with NIAID and NIH to assess whether casirivimab/imdevimab can be used to treat and prevent COVID-19 (NCT04452318) - A treatment arm of the RECOVERY trial added casirivimab/imdevimab to its list of potential COVID-19 treatments in September 2020. Outcomes: - Phase 1/2/3 outpatient trial: Results from the first 275 patients in the Phase 1/2/3 trial, published in NEJM, showed casirivimab/imdevimab was effective in reducing viral load, with patients who enrolled with a higher baseline viral level demonstrating greater decrease in viral load, reduction in symptoms, and hospital visits. Further results, also published in NEJM, showed the treatment reduced the risk for any-cause hospitalization or mortality compared with a placebo group (1.3% vs. 4.6%; P < .001).- Phase 1/2/3 hospitalized trial: Results from the trial presented at IDWeek 2021 showed casirivimab/imdevimab significantly reduced viral load in patients hospitalized with COVID-19 who did not mount their own immune response. Regeneron had previously announced results from a Phase 3 of 4,567 participants that showed the group of patients receiving intravenous casirivimab/imdevimab at 1,200 mg had a reduction in hospitalization or death of 70% (P = .0024), while the group that received 2,400 mg had a reduction by 71% (P < .0001). These results were presented at the ATS 2021 meeting, according to Regeneron.- Phase 3 prevention trial: In a trial that measured the ability of casirivimab/imdevimab to prevent COVID-19, results published in NEJM showed a relative risk reduction of 81.4% against symptomatic infection and 66.4% for symptomatic and asymptomatic infections for individuals living with someone with a confirmed SARS-CoV-2 infection. Results from an analysis out to 8 months, announced in a press release, showed a relative risk reduction of 81.6% for up to 8 months.- RECOVERY: For patients who had not mounted an antibody response on their own, REGN-COV significantly reduced mortality compared with usual care (24% vs. 30%; rate ratio, 0.80; 95% CI, 0.70-0.91; P = .001), but there was no significant difference between patients who had already mounted an antibody response and usual care (20% vs. 21%; RR, 0.96; 95% CI, 0.86-1.03; P = .17).- Mayo Clinic: Real-world data on the use of casirivimab/imdevimab as a treatment for high-risk patients with mild or moderate COVID-19, published in EClinicalMedicine, found the antibody cocktail reduces the risk of hospitalization at 14 days (1.3% vs. 3.3%), 21 days (1.3% vs. 4.2%) and 28 days (1.6% vs. 4.8%) compared with an untreated placebo group.Evidence in new variants:In a preprint posted to bioRxiv of results from a study by researchers at Columbia University, the combination of casirivimab and imdevimab maintained its neutralizing antibody response against the B.1.1.7 variant, and was "seemingly unaffected" by the B.1.351 variant of SARS-CoV-2 while losing "some neutralizing activity."Status: On 8 April, NIH updated its treatment guidelines for use of monoclonal antibodies against COVID-19 and strongly recommended using casirivimab/imdevimab for individuals with COVID-19 in an outpatient setting "who are at high risk of clinical progression" defined by the EUA. Based on results from the Phase 3 prevention trial, Regeneron said it is seeking an EUA for that indication with the FDA. The US government has agreed to purchase up to 3 million doses of casirivimab/imdevimab as of September 2021.On 26 May, the Assistant Secretary for Preparedness and Response (ASPR) and FDA released a statement that recommended healthcare providers in six states (Arizona, California, Florida, Indiana, Oregon, and Washington) stop distribution of bamlanivimab/etesevimab due to increased prevalence of COVID-19 variants P.1 (Gamma) variant and the B.1.351 (Beta) variant. In its place, ASPR and FDA recommended the use of REGEN-COV based on evidence it "retains activity" against these variants.

Last Update : 11/19/2021

Medication Class : Antiviral

Trade Name : AT-527

Developer Researcher : Atea Pharmaceuticals, Inc.

Sponsors : Atea Pharmaceuticals, Inc.

Trial Phase : Phase 2/3

Details : Background: Atea Pharmaceuticals, Inc. is developing an oral direct-acting antiviral drug AT-527 as a COVID-19 therapeutics candidate. Trials: The company is evaluating up to 190 participants in an international Phase 2 trial where patients 45-80 years old hospitalized with moderate COVID-19 will receive the drug or placebo for 5 days (NCT04396106). The Phase 2 MOONSONG trial of non-hospitalized patients with mild or moderate COVID-19 is also underway (NCT04709835). A Phase 3 trial taking place outside the US, MORNINGSKY, is currently underway (NCT04889040).Outcomes: Interim results from 70 participants from the Phase 2 study of hospitalized patients with moderate COVID-19, announced through a press release, showed AT-527 "rapidly reduced" viral load in patients who received the drug, with an 80% greater mean reduction in viral load seen at day 2 compared with placebo. However, AT-527 did not meet its primary endpoint of reduction in viral load compared with a placebo group, according to results from the Phase 2 MOONSONG trial announced in a press release by Atea.Status: The European Commission has listed AT-527 in its portfolio of ten most promising COVID-19 therapeutics in October 2021. Roche had previously worked jointly with Atea to develop AT-527; however, Atea announced on 16 November that the collaboration has ended.

Last Update : 11/19/2021

Medication Class : Synthetic human vasoactive intestinal peptide (VIP)

Trade Name : Zyesami (aviptadil, RLF-100)

Developer Researcher : NRx Pharmaceuticals,Relief Therapeutics

Sponsors : NRx Pharmaceuticals

Trial Phase : Phase 2/3

Details : Background: Zyesami (aviptadil; RLF-100) is thought to help decrease mortality and improve oxygenation in the blood for patients with COVID-19 through its anti-inflammatory activity. It currently has an Orphan Drug designation from the FDA and EMA for acute lung injury. Trials: Several clinical trials are planned or underway:- The 144-person AVICOVID-2 Phase 2/3 study evaluating the candidate’s effectiveness in treating non-acute lung injury (NCT04360096).- A treatment arm of the ACTIV-3b (ACTIV-3 Critical Care) TESICO trial in combination with Veklury, currently underway (NCT04843761).- The COVID-AIV trial evaluating patients with critical COVID-19 who have respiratory failure (NCT04311697). FDA also has granted an Expanded Access Protocol for patients ineligible for enrollment in COVID-AIV (NCT04453839).- A Phase 1 trial in Switzerland of up to 80 participants evaluating an inhaled form of Zyesami (NCT04536350).- Zyesami is also being evaluated in a treatment arm of the adaptive I-SPY COVID-19 clinical trial (NCT04488081).Regulatory Actions: Zyesami was granted a fast-track designation by the FDA for COVID-19 in mid-2020. On 2 June 2021, Relief Therapeutics announced that its partner NRx Pharmaceuticals applied for an EUA with the FDA for Zyesami to treat patients with critical COVID-19 in respiratory failure; FDA declined to issue an EUA in November 2021. The companies have requested a follow-up meeting, according to their statement.Outcomes: Early results from the first 30 patients enrolled in the COVID-AIV trial show no significant drug-related adverse events among patients taking Zyesami compared with placebo. Topline results from an open-label, prospective study show survival of 81% for patients hospitalized for COVID-19 who received Zyesami compared with the placebo group. Results from a Phase 2b/3 trial, announced by NRx Pharmaceuticals on 9 February, show that Zyesami did not meet its primary endpoint of differences in patient survival at 28 days, but did improve outcomes for patients receiving high flow nasal cannula therapy and mechanical ventilation, which included a median reduction of 5 days in hospital stay (P = .043). On 29 March, NRx Pharmaceuticals announced 60-day results from the Phase 2b/3 trial, which showed Zyesami was significantly associated with helping patients who were critically ill with COVID-19 recover from respiratory failure at 28 days (P = .014) and at 60 days (P = .013), and was significantly associated with survival (P ≤ .001). On 27 September, NRx Pharmaceuticals noted that participants in the Zyesami group in the Phase 2b/3 trial have a three-fold higher likelihood of being alive at 1 year compared with the group that received standard of care.

Last Update : 11/19/2021

Medication Class : IL-6 receptor agonist

Trade Name : Kevzara (sarilumab)

Developer Researcher : Sanofi,Regeneron

Sponsors : Sanofi,Regeneron

Trial Phase : Phase 2/3

Details : Background: Kevzara is indicated to treat moderately to severely active rheumatoid arthritis in adults with inadequate response or intolerance to one or more DMARDs. The drug is being evaluated for its potential benefit in reducing the inflammatory response in the lungs among patients with COVID-19 who develop acute respiratory distress syndrome.Regulatory Actions: The World Health Organization has recommended patients with severe or critical COVID-19 be prescribed an IL-6 receptor blocker such as Kevzara. In the United Kingdom, the National Health Service has asked providers to "consider prescribing" Kevzara for patients with pneumonia associated with COVID-19, but an authorization from MHRA has not been made.Trials: A Phase 2/3 trial of 400 patients sponsored by Sanofi and Regeneron has been completed in the United States (NCT04315298). A second, Phase 2/3 trial was conducted in Italy, Spain, Germany, France, Canada and Russia (NCT04324073).Outcome: Preliminary data from an Italian paper from the Gemelli Against COVID-19 group published in The Lancet indicates Kevzara may be a promising treatment for COVID-19, but concomitant administration of other treatments does not make it clear whether it was Kevzara that provided the benefit. The authors said 83% of patients had clinical improvement after administration. Results from a small study from the SARI-RAF Study Group published in Annals of the Rheumatic Diseases found Kevzara did not perform better than standard care for clinical improvement and mortality in patients with severe COVID-19. In the REMAP-CAP trial, results published in NEJM showed a median in-hospital survival of 2.01 (95% credible interval, 1.18-4.71) compared with the control group. Results from a subset of 148 patients in CORIMUNO-19, published in The Lancet Rheumatology, showed Kevzara did not reduce the need for mechanical ventilation, compared to placebo.Status: In a position statement updated on 8 January, NHS advised clinicians to use Actemra or Kevzara for patients with suspected or confirmed COVID-19 and severe pneumonia admitted to intensive care based on results from the REMAP-CAP trial. The international trial sponsored by Sanofi and the US trial sponsored by Regeneron have been halted. The international trial did not meet its primary endpoint, and the companies have said they are not continuing clinical studies for Kevzara. Results from the Phase 2 portion of the Regeneron trial released by the company on 27 April showed Kevzara was not effective in treating severe COVID-19 cases or critical cases requiring a ventilator. Regeneron continued the trial with critical cases only and discontinuing the lower-dose treatment arm (200 mg) in favor of the higher-dose arm (400 mg), but results from the Phase 3 portion of the trial showed Kevzara did not meet primary or secondary endpoints compared with supportive care.

Last Update : 11/19/2021

Medication Class : Antiviral

Trade Name : Ensovibep (MP0420)

Developer Researcher : Molecular Partners,Novartis

Sponsors : Molecular Partners,Novartis

Trial Phase : Phase 2/3

Details : Background: The antiviral ensovibep (formerly MP0420) is being developed by Molecular Partners AG in partnership with Novartis as a potential therapeutic for COVID-19. Trials: Ensovibep is being evaluated in a Phase 1 trial in the United Kingdom of up to 24 healthy participants (NCT04870164). A Phase 2a clinical trial in The Netherlands is studying ensovibep in 40 patients with symptomatic COVID-19 (NCT04834856). The candidate is also a treatment arm of Phase 3 ACTIV-3 trial, sponsored by the National Institutes of Health. A global Phase 2/3 trial, named EMPATHY, is evaluating ensovibep compared with placebo in up to 2,100 participants and is currently underway (NCT04828161). Outcomes: In initial results from the Phase 1 trial announced in a press release on 9 March, Molecular Partners said ensovibep was safe and well-tolerated in participants who received the therapeutic.Status: On 16 November, Molecular Partners announced that an independent data and safety monitoring board recommended halting enrollment of patients to ACTIV-3 after results of a futility analysis.

Last Update : 11/19/2021

Medication Class : Tyrosine kinase inhibitor

Trade Name : STI-5656 (abivertinib)

Developer Researcher : Sorrento Therapeutics

Sponsors : Sorrento Therapeutics

Trial Phase : Phase 2

Details : Background: Sorrento Therapeutics is testing a tyrosine kinase inhibitor STI-5656 (abivertinib maleate) in patients hospitalized with COVID-19 related pneumonia. The company licensed abivertinib from ACEA Therapeutics as a therapy for COVID-19. Trials: A Phase 2 trial of 80 participants receiving STI-5656 or standard of care in the US (NCT04440007), and a Phase 2 trial of up to 400 participants in Brazil (NCT04528667) have been completed.Outcomes: Preliminary results from the Phase 2 trial in the US showed patients in the STI-5656 group had a 20% improvement in avoiding respiratory failure and death at 1 month compared with placebo (78.3% vs. 58.3%). In the study located in Brazil, patients in the STI-5656 group had a 25% improvement in avoiding respiratory failure and death at 1 month compared with placebo (69.6% vs. 44.4%). Results from both trials were announced in a press release by Sorrento Therapeutics.Status: A Phase 3 trial is being planned based on positive results from both Phase 2 trials, according to the company.

Last Update : 11/5/2021

Medication Class : JAK inhibitor

Trade Name : Olumiant, Baricinix (baricitinib)

Developer Researcher : Eli Lilly

Sponsors : Eli Lilly,NIAID

Trial Phase : Phase 3/4

Details : Background: Olumiant (baricitinib), a Janus kinase (JAK) inhibitor developed by Eli Lilly and Company, is being evaluated as a therapeutic for COVID-19 alone and in combination with other therapies. Regulatory Actions: - Brazil: Approved for hospitalized patients with COVID-19 requiring supplemental oxygen on 17 September.- EU: As of 29 April, EMA is reviewing Olumiant as a potential treatment for patients with COVID-19 who are hospitalized and require supplemental oxygen. The EU has twice named Olumiant to its list of most promising therapeutics -- once in June 2021 and again in October 2021.- India: Olumiant tablets in doses of 2 mg and 4 mg have been granted permission for restricted emergency use of Olumiant in combination with Veklury. Following the announcement, Lilly said they were "accelerating" the availability of Olumiant in India.- Japan: Olumiant has received an endorsement from the Pharmaceutical Affairs and Food Sanitation Council in Japan, and a formal authorization is expected.- Mexico: Baracitinib was given a favorable recommendation for approval on 16 March.- US: On 19 November, FDA issued an EUA for Olumiant in combination with Veklury for adult and adolescent patients hospitalized with COVID-19 requiring supplemental oxygen, invasive mechanical ventilation, or ECMO, based on the results of the ACTT-2 trial. FDA issued an EUA for Olumiant alone on 28 July.Trials: Olumiant is being evaluated in the following high-profile trials: - The Phase 3 Adaptive COVID-19 Treatment Trial 2 (ACTT-2), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), where participants received Veklury alone or together with Olumiant (NCT04401579) - The Adaptive COVID-19 Treatment Trial 4 (ACTT-4), sponsored by NIAID, is evaluating a combination of baricitinib and Veklury compared to a combination of dexamethasone and Veklury (NCT04640168). - The Phase 3 COV-BARRIER trial, sponsored by Eli Lilly, evaluating Olumiant against placebo in hospitalized COVID-19 patients (NCT04421027) - The Phase 4 TACTIC-R study evaluating Olumiant and ravulizumab against standard of care (NCT04390464) Outcomes: - ACTT-2: In this trial, Olumiant plus Veklury significantly shortened median time to recovery from 8 days to 7 days compared with Veklury alone (HR, 1.15; 95% CI, 1.00-1.31; P = .047). Patients receiving Olumiant plus Veklury also had a significantly increased likelihood of better clinical status at 15 days (odds ratio, 1.26; 95% CI, 1.01-1.57; P = .044) and significantly fewer patients progressing to mechanical ventilation or mortality (23% vs. 28%; OR, 0.74; 95% CI, 0.56-0.99; P = .039). The results were published in NEJM.- Bangladesh: In a prospective cohort study published in BMC Infectious Diseases, a higher dose (8 mg daily) of Olumiant given to patients with severe COVID-19 was associated with improved early stability of respiratory functions, and fewer ICU visits and intubation requirements compared with patients who received a usual dose (4 mg daily) of Olumiant.- COV-BARRIER: Results from the Phase 3 trial published in The Lancet Respiratory Medicine showed patients hospitalized with COVID-19 were 2.7% less likely to progress to mechanical ventilation or die during the trial, which was not statistically significant (odds ratio, 0.85; 95% CI, 0.67-1.08; P = .18). However, significantly fewer patients in the Olumiant group reached 60-day all-cause mortality compared with patients in the placebo group (10% vs. 15%; HR, 0.62; 95% CI, 0.47–0.83; p = .005).Status: On 15 April, NIH closed enrollment in the ACTT-4 trial after finding that neither treatment regimen was more effective at preventing adults hospitalized with COVID-19 on supplemental oxygen from progressing to requiring mechanical ventilation or death, among other outcomes.

Last Update : 11/5/2021

Medication Class : Antiviral

Trade Name : SNG001

Developer Researcher : Synairgen

Sponsors : Synairgen

Trial Phase : Phase 2/3

Details : Background: SNG001 is an an inhaled formulation of interferon-beta-1a made by UK-based biotechnology company Synairgen. Originally developed as a potential treatment for asthma and chronic obstructive pulmonary disease (COPD), it is being investigated as a therapeutic candidate for COVID-19. Trials: Synairgen has launched a Phase 2 trial evaluating SNG001 of up to 820 participants in a hospital  setting and at home (NCT04385095; EudraCT: 2020-001023-14), and the Phase 3, randomized, double-blinded, placebo-controlled SPRINTER trial of up to 610 participants, which is currently recruiting (NCT04732949). SNG001 is also being evaluated in a substudy of the Phase 2/3 ACTIV-2 trial (NCT04518410); the therapeutic advanced to the Phase 3 portion of the trial in October 2021. Outcomes: Results from 101 patients in the Phase 2 trial published in The Lancet Respiratory Medicine showed patients in the SNG001 group had better improvement as measured by the WHO Ordinal Scale for Clinical Improvement (odds ratio, 2.32; 95% confidence interval, 1.07-5.04; P = .033) at 15-16 days after treatment compared with placebo; SNG001 was described as well tolerated, and there were no deaths in the intervention group compared with three deaths in the placebo group. Results from their Phase 2 trial, announced through a press release, showed patients who were "markedly or severely breathless" and received SNG001 at home or in the hospital were 3.41 times more likely to recover compared with patients who received placebo (P = .004).

Last Update : 11/5/2021

Medication Class : Monoclonal antibody

Trade Name : Otilimab

Developer Researcher : MorphoSys,GSK

Sponsors : GSK

Trial Phase : No longer being studied for COVID-19

Details : Background: Otilimab is an anti-GM-CSF antibody developed and currently being evaluated for rheumatoid arthritis. GSK has identified the drug as a potential candidate for COVID-19 treatment in patients who experience cytokine release syndrome. Trials: GSK is sponsoring the randomized Phase 2 OSCAR trial of 800 participants with COVID-19 who will receive standard of care plus either a single IV infusion of otilimab or placebo (NCT04376684). Outcomes: Results from the OSCAR trial were announced by GSK on 25 February, which showed a non-significant treatment difference of 5.3% among participants receiving otilimab compared with placebo (95% CI, -0.8% to 11.4%). Among 180 participants who were at least 70 years old, 65.1% reached 28-day follow-up without respiratory failure compared with 45.9% of participants in the placebo group (95% CI, 5.2-33.1%; P = .009) and there was a treatment difference in mortality of 14.4% in these participants at 60 days compared with placebo (40.4% vs. 26%; 95% CI, 0.9-27.9%; P = .040). Status: OSCAR is currently active, but not recruiting; GSK announced in February 2021 it would amend the OSCAR trial to include older participants based on initial positive results seen in patients 70 years and older. In a Q3 press release, GSK announced it would no longer be evaluating otilimab as a COVID-19 therapeutic due to the success of sotrovimab as a treatment for patients with mild or moderate COVID-19.

Last Update : 11/5/2021

Medication Class : Interleukin-1 receptor antagonist

Trade Name : Kineret (anakinra)

Developer Researcher : Sobi, Inc.

Sponsors : Various

Trial Phase : Various

Details : Background: Kineret (anakinra) is an interleukin-1 receptor agonist developed by Sobi Inc. and being repurposed as a COVID-19 therapeutics candidate. It is used to treat patients with rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease.Trials: High-profile trials evaluating Kineret for COVID-19 include:- ANA-COVID-GEAS: A Phase 2/3 trial in Spain testing Kineret in COVID-19 patients with cytokine release syndrome (NCT04443881)- COV-AID: A Phase 3 trial in Belgium is testing Kineret against Actemra, siltuximab, and usual care in patients with respiratory failure and cytokine release syndrome associated with COVID-19 (NCT04330638)- ImmCoVA: A Phase 3 study in Sweden evaluating Kineret against Actemra and standard of care (NCT04412291)- RECOVERY: Kineret is a treatment arm of the Phase 2/3 RECOVERY trial (NCT04381936)- REMAP-CAP: Kineret is also a treatment arm of the Phase 4 REMAP-CAP trial (NCT02735707)- SAVE: A Phase 2 trial in Greece testing whether Kineret can prevent progression to severe respiratory failure in participants with COVID-19 (NCT04357366)- SAVE-MORE: An international Phase 3 trial comparing Kineret against placebo in participants with severe respiratory failure (NCT04680949)- SOBI: A Phase 2 trial in Sweden evaluating Kineret in participants with cytokine release syndrome (NCT04603742)- University of Alabama: Kineret is being tested against a saline solution as a potential early treatment for cytokine storm syndrome in a Phase 3 trial (NCT04362111)Outcomes: Data from 9 studies appear to show treatment with Kineret reduced risk of mortality (odds ratio, 0.32; P < .00001) and need for mechanical ventilation (OR, 0.38; P = .02) in intubated COVID-19 patients, according to a meta-analysis published in Rheumatology. Results from the SAVE-MORE trial, published in Nature Medicine, showed a 64% reduction in progression to worse clinical status and 55% relative decrease in mortality at 28 days for patients with COVID-19 at risk of progression to respiratory failure.Regulatory Actions: EMA is evaluating Kineret as a potential treatment option for patients with COVID-19 associated pneumonia at risk for respiratory failure. The European Commission has listed Kineret (under the name anakinra) as one of the ten most promising COVID-19 therapeutics as of October 2021.

Last Update : 10/22/2021

Medication Class : Antiviral

Trade Name : Veklury (remdesivir)

Developer Researcher : Gilead Sciences

Sponsors : Gilead Sciences

Trial Phase : Phase 2/3

Details : Background: Veklury is a broad-spectrum antiviral that is delivered intravenously. It was originally developed as a treatment for Ebola. Regulatory actions: Veklury has been approved or authorized for emergency/temporary use in about 50 countries, including Argentina, Bahrain, Guatemala, Jordan, Kuwait, Lebanon, Qatar, Saudi Arabia, and Turkey, according to Gilead Sciences.- Australia: Provisionally approved to treat COVID-19 patients 12 years and older with pneumonia who require supplemental oxygen.- Brazil: Authorized for use in the country by ANVISA on 12 March in patients 12 years or older who are hospitalized with COVID-19 requiring oxygen.- Canada: Authorized for use in the country with conditions in July 2020 based on results from the ACTT-1 trial. In November 2020, Health Canada said it was monitoring Veklury based on WHO recommendations, but did not make any changes to Veklury's authorization in Canada.- EU: Conditional marketing authority to treat COVID-19 patients aged 12 years and older with pneumonia who require supplemental oxygen.- Iceland: Conditional marketing authority to treat COVID-19 patients aged 12 years and older with pneumonia who require supplemental oxygen.- Hong Kong: Registered for use on 17 July 2020.- India: A powder form of Veklury was approved for use on 6 July 2020, according to Mylan.- Iraq: Authorized for use on 23 August 2020.- Japan: Special approval for emergency granted 4 May 2020. - Mexico: Authorized for emergency use by COFEPRIS on 12 March.- Russia: Approved for use on 14 October 2020.- Singapore: Conditionally approved for use in adult COVID-19 patients with oxygen saturation less than 94% on room air, under invasive mechanical ventilation, or on ECMO (extracorporeal membrane oxygenation).- South Korea: Approved for use by MFDS on 3 June 2020.- Switzerland: Temporary authorization issued 25 November.- Taiwan: Conditionally approved for use on 11 June 2020.- UK: Approved to treat COVID-19 patients aged 12 years and older with pneumonia who require supplemental oxygen.- UAE: Authorized for use in United Arab Emirates.- US: Veklury is approved by the FDA for use in adults and adolescents hospitalized for COVID-19. The approval is based on results from the ACTT-1 trial, sponsored by NIAID, and the two SIMPLE trials sponsored by Gilead. FDA has warned Veklury should not be used with hydroxychloroquine or chloroquine phosphate, as it may reduce antiviral activity. FDA has also issued an EUA for Veklury in combination with the JAK inhibitor Olumiant for hospitalized patients with COVID-19 requiring mechanical ventilation, based on results from the ACTT-2 trial. Trials: Veklury is being evaluated in the following high-profile trials:- SOLIDARITY (ISRCTN83971151) (NCT04315948)- SIMPLE (NCT04292730; NCT04292899) - ACTT (NCT04280705), ACTT-2 (NCT04401579), ACTT-3 (NCT04492475), and ACTT-4 (NCT04640168). - Capital Medical University (NCT04252664; NCT04257656). - A late-stage trial evaluating Veklury in pediatric patients with COVID-19. - A Phase 2 trial of 40 participants across multiple trial sites in the U.S. of Veklury with and without the oral broad-spectrum anti-viral drug merimepodib (NCT04410354). - Gilead is testing an inhaled version of Veklury in a Phase 1a trial. - IMPAACT 2032, an NIH-sponsored study evaluating the pharmacokinetics and safety of Veklury in pregnant women with COVID-19 (NCT04582266).- A treatment arm of the ACTIV-3b (ACTIV-3 Critical Care) TESICO trial in combination with Zyesami, currently underway (NCT04843761).- PINETREE, a Phase 3 trial evaluating Veklury's effectiveness at reducing the risk of COVID-19 associated hospitalization or mortality in outpatients (NCT04501952).Outcomes: - ACTT-1 and ACTT-2: Results from 1,059 patients in the ACTT study showed Veklury improved time to clinical recovery from 15 days to a median of 11 days, which was reaffirmed in a final report published in NEJM. In ACTT-2, where patients received baricitinib in combination with Veklury, the group that received baricitinib had a reduced time to recovery compared with patients who received Veklury alone.- ACTT-3: In the Phase 3 ACTT-3 trial, adding interferon beta-1a to Veklury increased the number of adverse events for patients hospitalized with COVID-19 and pneumonia compared with Veklury alone, according to a study published in The Lancet Respiratory Medicine.- ACTT-4: On 15 April, NIH closed enrollment in the ACTT-4 trial after finding that neither treatment regimen was more effective at preventing adults hospitalized with COVID-19 on supplemental oxygen from progressing to requiring mechanical ventilation or death, among other outcomes.- Capital Medical University: Veklury did not significantly improve clinical symptoms (hazard ratio, 1.23; 95% CI, 0.87-1.75). - SIMPLE: Results from Gilead’s two trials showed greater clinical improvement in moderate and severe COVID-19 cases, but results have not been statistically significant. Further results from the SIMPLE trial evaluating severe COVID-19 cases showed an improved time to clinical improvement and 62% reduction in mortality. In patients with moderate COVID-19, results from a large international trial published in JAMA appeared to show clinical improvement in patients taking a 5-day course of Veklury compared with patients randomized to standard of care at 11 days, "but the difference was of uncertain clinical importance." - SOLIDARITY: Interim trial results from SOLIDARITY published in NEJM showed none of the study drugs, including Veklury, reduced mortality, need for ventilation, or duration of hospital stay. These results were affirmed in a separate study analyzing SOLIDARITY's results, which was published in The Lancet Infectious Diseases.- NOR-Solidarity: An add-on trial to SOLIDARITY, with results published in the Annals of Internal Medicine, showed there was no significant difference in viral clearance between Veklury and hydroxychloroquine groups.- PINETREE: Veklury reduced the risk of progression to hospitalization or death by 87% in 562 participants with COVID-19 in an outpatient setting, according to a Gilead press release.- Johns Hopkins: Results published in JAMA Network Open of 2,483 mostly non-White patients who received care for COVID-19 at Johns Hopkins Health System showed Veklury was associated with reduced time to clinical improvement.- Veterans Health Administration: A study of veterans hospitalized with COVID-19 who received Veklury showed the drug did not improve survival, but it did increase length of hospital stay. The results were published in JAMA Network Open.- Real-world data: Results from several real-world studies announced by Gilead in a press release showed that Veklury significantly reduced mortality by 70% in a subset of patients hospitalized with COVID-19 and low-flow oxygen requirements at baseline (4% vs. 13%; hazard ratio, 0.30, 95% confidence interval, 0.14-0.64).Status: On 19 November, the World Health Organization’s (WHO’s) Guideline Development Group released a statement recommending against the use of Veklury regardless of illness severity. Gilead released a statement on 21 January that they believe Veklury is still effective against new SARS-CoV-2 variants. On 12 April, Gilead announced it would stop a trial evaluating intravenous Veklury in patients with COVID-19 in a non-hospital setting.

Last Update : 10/22/2021

Medication Class : Glucocorticoid

Trade Name : Dexamethasone (many brands and generics)

Developer Researcher : Various

Sponsors : University of Oxford

Trial Phase : Phase 2/3

Details : Background: Dexamethasone has the potential for reducing the inflammation associated with cytokine release syndrome in patients with COVID-19. Trials: The drug is being evaluated as a treatment arm of the RECOVERY trial. It is also being evaluated in the Adaptive COVID-19 Treatment Trial 4 (ACTT-4) in combination with Veklury against Olumiant plus Veklury (NCT04640168). Outcomes: - CoDEX: Results from the CoDEX trial (NCT04327401) in Brazil showed patients taking dexamethasone had a significant increase in the number of ventilator-free days at 28 days compared with standard of care, according to a paper published in JAMA. CoDEX was stopped early due to results from the RECOVERY trial.- RECOVERY: Preliminary results from the RECOVERY trial published in the NEJM indicate dexamethasone may help reduce mortality in patients with COVID-19. Of 2,104 patients randomized to receive dexamethasone, the mortality rate was significantly lower in patients on mechanical ventilators compared with those who received usual care (29.3% vs. 41.4%) and in patients receiving oxygen compared with those who received usual care (23.3% vs. 26.2%). - Results from a small retrospective study of 59 patients published in Tuberculosis & Respiratory Diseases showed early use of dexamethasone may help patients with COVID-19 from developing severe disease, but the treatment did not significantly improve mortality. - A retrospective study published in the Journal of Inflammation Research found patients with severe COVID-19 who received Actemra had a significantly lower mortality rate compared with patients who received Actemra plus dexamethasone or dexamethasone alone.- COVID STEROID 2: A trial evaluating the difference in the number of days alive without life support for patients with COVID-19 and hypoxemia found no significant difference in outcomes between patients who received 12 mg vs. 6 mg of dexamethasone, according to results published in JAMA.Regulatory Actions: In response to positive preliminary results, the UK and Japan have authorized dexamethasone to treat COVID-19. Dexamethasone is provisionally approved in Taiwan. The therapy also has been endorsed by the EMA for use in patients who require oxygen therapy. A formulation of dexamethasone, known as Dexamethasone Taw, was submitted to EMA by Taw Pharma in September for marketing authorization, but was withdrawn on 25 January.Status: On 15 April, NIH closed enrollment in the ACTT-4 trial after finding that neither treatment regimen was more effective at preventing adults hospitalized with COVID-19 on supplemental oxygen from progressing to requiring mechanical ventilation or death, among other outcomes.

Last Update : 10/22/2021

Medication Class : Antigout agent

Trade Name : Colchicine (Mitigare, Colcrys)

Developer Researcher : NHLBI,Bill and Melinda Gates Foundation,Government of Quebec

Sponsors : Montreal Heart Institute

Trial Phase : Phase 2/3

Details : Background: Colchicine, an anti-inflammatory drug primarily used to treat gout, is being evaluated as a therapeutic candidate for COVID-19. Pre-clinical studies have shown use of colchicine reduces lung injury in patients with ARDS, and could be useful for the treatment of severe COVID-19 symptoms. Trial: Colchicine is being evaluated in the following high-profile trials: - A treatment arm of the RECOVERY trial (NCT04381936). - COLVID-19: a Phase 2 multicenter, randomized, open-label study of up to 308 participants at the University Of Perugia in Italy (NCT04375202). - COLHEART-19: A Phase 2 study of up to 150 participants at the University of California, Los Angeles (NCT04355143) and the Miami Cardiac and Vascular Institute (NCT04510038). - COLCOVID: A 2,500-person Phase 3 trial at the Estudios Clínicos Latino América in Argentina evaluating colchicine against standard of care (NCT04328480), at the Dhaka Medical College in Bangladesh (NCT04527562), and at the Fundación Universitaria de Ciencias de la Salud in Columbia (NCT04539873). - COLCHI-COVID: A Phase 3 trial of up to up to 954 participants at the Instituto de Investigación Marqués de Valdecilla in Spain (NCT04416334). - COLCORONA: Researchers at the Montreal Heart Institute are evaluating colchicine in a Phase 3 randomized, double-blind, placebo-controlled trial of up to 6,000 participants with high-risk COVID-19 (NCT04322682). - PRINCIPLE: A treatment arm of the PRINCIPLE trial compared with usual care. Outcomes: - COLCORONA: In a press release, the Montreal Heart Institute (MHI) said results from the COLCORONA trial showed patients who received colchicine had a 21% reduction in hospitalization or mortality compared with placebo. However, in results published in The Lancet Respiratory Medicine, the colchicine group did not meet the primary endpoint of death or hospital admission due to COVID-19 compared with a placebo group (4.7% vs. 5.8%; P = .081). - Parma University Hospital: A retrospective study of 141 patients with COVID-19 in Parma University Hospital in Italy, published in PLoS One, showed the 21-day cumulative mortality rate was 7.5% for patients who received colchicine compared with 28.5% who did not receive colchicine (P = .006; adjusted hazard ratio, 0.24; 95% CI, 0.09-0.67), with 40% of patients in the colchicine group experiencing clinical improvement compared with 26.6% of patients in the control group.- RECOVERY: Compared with patients with COVID-19 receiving usual care, those who received colchicine did not show improved 28-day mortality, hospital stay, or reduced risk of invasive mechanical ventilation or death, according to a study published in The Lancet Respiratory Medicine.- University of Sao Paulo: Results from researchers in Brazil published in the journal RMD Open showed that, compared with placebo, patients receiving colchicine had a reduced number of days on supplemental oxygen (4 days vs. 6.5 days; P < .001) and the lower median number of days hospitalized (7 days vs. 9 days; P = .003). Status: RECOVERY closed recruitment for the colchicine arm of their trial in March 2021 after a data monitoring committee found "no convincing evidence that further recruitment would provide conclusive proof of worthwhile mortality benefit either overall or in any pre-specified subgroup." Guidelines for COVID-19 treatment released by the UK National Institute for Health and Care Excellence (NICE) updated on 3 June strongly recommend against using colchicine to treat COVID-19 in a hospital setting.

Last Update : 10/8/2021

Medication Class : H2 blocker

Trade Name : Pepcid (famotidine)

Developer Researcher : Yamanouchi Pharmaceutical Co.,J&J,Merck

Sponsors : Northwell Health

Trial Phase : Phase 3

Details : Background: Pepcid is mainly used to treat peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. Pepcid was identified by computer models as having the potential for inhibiting 3-chymotrypsin-like protease, which controls coronavirus replication. Trials: The drug was studied in the now-completed Phase 3 MATCH trial, where up to 1,170 participants received hydroxychloroquine either with and without Pepcid (NCT04370262). Outcomes: Evidence of benefit: A large retrospective study performed by researchers from the MATCH trial found patients with COVID-19 taking Pepcid (n = 84) were significantly less likely to experience death or intubation as a composite outcome (P < .01) compared with patients not taking Pepcid (n = 1,536). Results from a small observational study of 83 patients hospitalized for COVID-19 at a tertiary care center who received Pepcid had reduced mortality, lower rates of intubation, and reduced serum markers. A small case series of 10 patients with COVID-19 in a non-hospital setting found high doses of the medication (most commonly 80 mg three times per day over median 11 days) improved disease-related symptoms. Evidence of no benefit: In a large study published in the journal Gastroenterology of 1,127 patients with COVID-19 who received Pepcid and 6,031 patients who did not, results showed Pepcid did not reduce the risk of death. Another study that examined outcomes for patients taking proton pump inhibitors, hydroxychloroquine, or Pepcid compared with patients not taking Pepcid, published in The American Journal of Gastroenterology, there was no significant different in hospitalization or mortality for patients taking Pepcid compared with those not taking Pepcid. Results from a pre-print paper suggest Pepcid is not a “direct-acting inhibitor” of the virus. Pepcid does not appear to improve in-hospital mortality (28.3% vs. 28.2%), according to a study published in the Journal of Medical Virology.

Last Update : 10/8/2021

Medication Class : Immunoglobulin

Trade Name : Intravenous immunoglobulin (IVIG)

Developer Researcher : Various

Sponsors : Various

Trial Phase : Phase 2/3/4

Details : Background: Intravenous immunoglobulin (IVIG) is a therapy being considered as a potential treatment for COVID-19. Trials: A number of trials around the world are examining IVIG as a COVID-19 therapeutic, including:- Two Phase 3 NIAID-sponsored trials evaluating IVIG as an inpatient (NCT04546581) and outpatient (INSIGHT-012; NCT04910269) treatment for COVID-19.- A Phase 3 trial sponsored by Octopharma evaluating a version of IVIG called Octagam 10% for patients with severe COVID-19 (NCT04400058).- Two Phase 4 trials sponsored by Sharp HealthCare evaluating IVIG as a COVID-19 treatment compared with standard of care (NCT04411667), and for patients with COVID-19 requiring mechanical ventilation (NCT04616001). - Two Phase 2 trials in Spain sponsored by Grifols Therapeutics evaluating IVIG in patients hospitalized with COVID-19 (NCT04432324) and in intensive care (NCT04480424).- A completed Phase 1/2 trial examining IVIG as an antibody therapy for COVID-19 (NCT04521309), and a Phase 2/3 trial evaluating IVIG for patients with severe COVID-19 (NCT04891172); both trials were sponsored by Dow University of Health Sciences in Pakistan.Outcomes: In a retrospective study of multisystem inflammatory syndrome in children (MIS-C) after a SARS-CoV-2 infection, patients who received a course of IVIG plus infliximab were less likely to require additional therapy compared with children who received IVIG alone (31% vs. 65%; P = .01).

Last Update : 10/8/2021

Medication Class : Sphingosine kinase 2 inhibitor

Trade Name : Opaganib

Developer Researcher : RedHill Biopharma

Sponsors : RedHill Biopharma

Trial Phase : Phase 2/3

Details : Background: Opaganib is a sphingosine kinase-2 (SK2) inhibitor developed by RedHill Biopharma being considered as a COVID-19 therapeutic. Trials: The SK2 inhibitor is being evaluated as a treatment for COVID-19 associated pneumonia in a Phase 2 trial in the United States and Israel (NCT04414618), and a Phase 2/3 international trial (NCT04467840) compared with a placebo group that also received Veklury and/or dexamethasone as standard of care; both trials have been completed.Outcomes: Results from the Phase 2 trial, announced through a press release in June 2021, showed 50% of 22 patients in the opaganib group no longer required supplemental oxygen compared with 22% of 18 patients who received a placebo; the result was consistent regardless of whether the patients were taking Veklury and/or dexamethasone. In an announcement on 26 August, RedHill Biopharma said opaganib was effective at inhibiting the B.1.617.2 (Delta) variant of SARS-CoV-2. The international Phase 2/3 trial did not meet its primary endpoint of a significant proportion of patients in the opaganib group no longer requiring supplemental oxygen at 14 days compared with the group that received standard of care, according to a press release from RedHill Biopharma.

Last Update : 10/8/2021

Medication Class : Monoclonal antibody

Trade Name : Remicade (infliximab)

Developer Researcher : Janssen

Sponsors : UHB,Birmingham National Institute for Health Research Biomedical Research Centre (NIHR BRC),NCATS,BARDA

Trial Phase : Phase 2/3

Details : Background: Remicade is a tumor necrosis factor inhibitor that been proposed as a potential treatment for cytokine release syndrome associated with COVID-19. Trials: Together with the monoclonal antibody namilumab, Remicade is being tested in patients hospitalized with COVID-19 in the multi-arm CATALYST trial of therapeutics led by researchers from the Universities of Birmingham and Oxford. Researchers hope one or both therapies will help alleviate serious symptoms of the disease. Remicade is also a treatment arm of the ACTIV-1 IM trial led by the National Center for Advancing Translational Sciences (NCATS), which is part of the National Institutes of Health (NCT04593940). Remicade is being tested as a treatment arm of Solidarity PLUS, the next phase of the Solidarity trial (ISRCTN18066414) (2020-001784-88).Outcomes: SARS-CoV-2 antibody concentrations were lower in patients taking Remicade who had their first dose of Pfizer/BioNTech's Comirnaty vaccine and AstraZeneca's Vaxzevria, according to research published in the journal Gut. However, seroconversion rates were higher in individuals who had received both doses of Comirnaty or had a previous SARS-CoV-2 infection. In a retrospective study of multisystem inflammatory syndrome in children (MIS-C) after a SARS-CoV-2 infection, patients who received course of IVIG plus infliximab were less likely to require additional therapy compared with children who received IVIG alone (31% vs. 65%; P = .01).

Last Update : 10/8/2021

Medication Class : Oral antiviral

Trade Name : TEMPOL (4-Hydroxy-TEMPO)

Developer Researcher : Adamis Pharmaceuticals Corporation,NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development

Sponsors : Adamis Pharmaceuticals Corporation

Trial Phase : Phase 2/3

Details : Background: TEMPOL is an oral antiviral drug being evaluated as a potential at-home therapeutic for COVID-19. Researchers believe TEMPOL can help to break up clusters of iron and sulfur cells that SARS-CoV-2 uses to replicate. Additionally, researchers noted TEMPOL has anti-cytokine and anti-inflammatory properties.Trial: A Phase 2/3 trial is currently recruiting up to 248 participants to test whether TEMPOL can limit hospitalization in patients with an early SARS-CoV-2 infection (NCT04729595). At least 50 individuals in the study enrolled will have comorbidities, according to the ClinicalTrials.gov listing.

Last Update : 10/8/2021

Medication Class : Nitric oxide

Trade Name : INOpulse

Developer Researcher : Bellerophon Therapeutics

Sponsors : Bellerophon Therapeutics

Trial Phase : No longer being studied for COVID-19

Details : Background: Inhaled nitric oxide has been explored as a treatment for COVID-19 patients due to its success in improving arterial oxygenation in patients with ARDS due to SARS-CoV. Results from patients treated with INOpulse under an emergency expanded access program have proved promising, the company said. Regulatory Actions: FDA allowed INOpulse for compassionate use in COVID-19 patients on 20 March. The FDA approved an IND for the therapy to proceed to a Phase 3 trial.Trials: Bellerophon is performing the Phase 3 randomized, placebo-controlled COViNOX study to evaluate the safety and efficacy of INOpulse in up to 500 COVID-19 patients where supplemental oxygen is needed prior to mechanical ventilation. The primary endpoints are respiratory failure and mortality of patients in both groups (NCT04421508).Results: A study published 29 September in Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine examining the effects of inhaled nitric oxide for patients with COVID-19 associated respiratory failure found there was no change in oxygen requirements for patients regardless of whether they received inhaled nitric oxide or high-flow nasal cannula.Status: In an update on the company's financial results, Bellerophon said it is pursuing INOpulse for multiple indications, but they would be discontinuing the COViNOX trial due to lack of efficacy and the availability of COVID-19 vaccines.

Last Update : 8/30/2021

Medication Class : Antimalarial

Trade Name : Pyramax (artesunate/pyronaridine)

Developer Researcher : Shin Poong Pharmaceutical Co., Ltd

Sponsors : Shin Poong Pharmaceutical Co., Ltd

Trial Phase : Phase 2/3

Details : Background: Pyramax (artesunate/pyronaridine) is an antimalarial drug combination being evaluated as a therapeutic candidate for COVID-19. It has been shown to inhibit SARS-CoV-2 in vitro, according to a pre-print paper posted to bioRxiv. Trials: The drug combination is being evaluated in several trials: a Phase 2 study of patients with mild or moderate COVID-19 in South Korea (NCT04475107), a Phase 2 trial in South Africa (NCT04532931), the Phase 2/3 PROVIDENCE trial in the Philippines (NCT04701606), and the Phase 3 MALCOV trial in Western Kenya and Burkina Faso (NCT04695197).Outcomes: Results from the Phase 2 study in South Korea showed Pyramax did not meet the primary outcome of reduction in viral load, but patients who received Pyramax did have a non-significantly lower clinical improvement (3.8%) compared with patients who received placebo (8.6%).

Last Update : 8/30/2021

Medication Class : Artemisinin

Trade Name : Artesunate

Developer Researcher : Liu Xu

Sponsors : Various

Trial Phase : Phase 2

Details : Background: Artesunate is an antimalarial drug being considered as a potential COVID-19 therapeutic.Trials: Artesunate is being tested as a treatment arm of Solidarity PLUS, the next phase of the Solidarity trial (ISRCTN18066414)(2020-001784-88). Researchers at the University of Kentucky Markey Cancer Center are also evaluating artesunate in a multi-arm Phase 2 trial with ivermectin, camostat mesilate , and the dietary supplement artemesia annua (NCT04374019).

Last Update : 8/30/2021

Medication Class : Single domain-based anti-COVID-19 antibody (VHH-Fc)

Trade Name : XVR011

Developer Researcher : ExeVir Bio BV

Sponsors : ExeVir Bio BV

Trial Phase : Phase 1

Details : Background: XVR011 is a single domain-based anti-COVID-19 antibody (VHH-Fc) that is designed to stop viral replication by inactivating the spike protein and blocks spike binding to ACE2. Pre-clinical data have shown the antibody inhibits SARS-CoV-2 replication in mouse and hamster models.Trials: A Phase 1 trial is underway that aims to evaluate the safety, efficacy, and appropriate dose for XVR011 in patients hospitalized for COVID-19 and receiving standard of care (NCT04884295).

Last Update : 8/13/2021

Medication Class : Monoclonal antibody

Trade Name : Vyrologix (PRO 140, leronlimab)

Developer Researcher : CytoDyn

Sponsors : CytoDyn

Trial Phase : Phase 2b/3

Details : Background: Leronlimab (also known as Vyrologix and PRO 140) is a CCR5 antagonist that blocks the CCR5 co-receptor on the surface of immune cells like CD4 cells. It is believed that leronlimab can enhance the immune response in patients experiencing cytokine release syndrome from respiratory distress caused by COVID-19. Regulatory Actions: Use of leronlimab in COVID-19 patients was authorized by FDA under an eIND very early in the pandemic (March 2020). On 17 May 2021, FDA issued a statement on leronlimab, based on CytoDyn's CD10 and CD12 trials, noting that "the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19." The CD10 trial did not meet its primary and secondary endpoints. CD12 did not meet its primary endpoint, and FDA noted CytoDyn's analysis of mortality in a subgroup of patients with severe COVID-19 in the CD12 trial was unbalanced and did not meet "statistical significance when using established and reliable analytical methods that correct for multiple comparisons."Trials: CytoDyn launched the Phase 2 CD10 trial evaluating leronlimab in patients with mild to moderate (NCT04343651), which is active but not currently recruiting. The CD12 trial, a Phase 2b/3 trial evaluating patients with severe (NCT04347239) cases of COVID-19, is currently recruiting. A Phase 2 trial testing leronlimab in patients with long-haul COVID-19 is active but not recruiting (NCT04678830). Another trial in collaboration with the Mexican National Institutes of Health is planned. A Phase 3 trial evaluating leronlimab in patients with severe COVID-19 has been approved in Brazil. A trial in Israel is set to begin in summer 2021.Outcomes: A pre-print of results from the trial evaluating severely or critically ill COVID-19 patients showed leronlimab was effective at reducing IL-6 expression and in reversing immunosuppression, which led to a lower plasma viral load. Topline results released by the company from a Phase 2 trial of mild-to-moderate COVID-19 patients found leronlimab had an improvement in total clinical symptom score compared with placebo (90% vs. 71%). Phase 3 results from a subset of patients who were critically ill, released by the company on 5 March, show a 24% reduction in mortality; however, the trial did not reach its primary endpoint, and the overall results of the trial are unclear. CytoDyn claimed in a press release that further results from a trial with a subgroup of 62 patients who had severe-to-critically ill COVID-19 showed leronlimab decreased the mortality rate by 82% at 14 days (P = .0233), but this analysis has been widely criticized (see Regulatory Actions section for FDA statement). Results from the CD15 trial of patients with long-haul COVID-19 showed "greater improvement in the leronlimab patient group over placebo in 18 of 24 COVID-19 symptoms." CD15 was not designed to measure statistical significance, CytoDyn said, and a follow-up trial is needed to confirm results.Status: CytoDyn has said it has submitted leronlimab trial data to the MHRA, Health Canada, and FDA for review.

Last Update : 8/13/2021

Medication Class : Tyrosine kinase inhibitor

Trade Name : Gleevec/Glivec (imatinib)

Developer Researcher : Novartis

Sponsors : Various

Trial Phase : Phase 2/3

Details : Background: Gleevec/Glivec (imatinib) is a tyrosine kinase inhibitor used to treat cancers such as chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. It is being evaluated as a potential therapeutic for COVID-19 in patients with pneumonia, who have cases requiring hospitalization or need mechanical ventilation.Trials: There are a number of trials evaluating Gleevec as a therapeutic: - As a treatment arm of Solidarity PLUS, the next phase of the Solidarity trial (ISRCTN18066414)(2020-001784-88);- A Phase 3 placebo-controlled trial of hospitalized adults with COVID-19 sponsored by the University of Maryland, Baltimore (NCT04394416);- A Phase 3 trial of patients with COVID-19 associated pneumonia at Alexandria University and the Science, Technology & Innovation Funding Authority in Egypt (NCT04422678);- The Phase 2 Covid19COVINIB trial comparing Gleevec, baricitinib, and placebo in patients with COVID-19 associated pneumonia in Spain (NCT04346147);- The Phase 2 IMPRESS COVID trial, sponsored by Exvastat, examining how Gleevec impacts oxygen in the lungs and blood of patients with COVID-19 requiring mechanical ventilation (NCT04953052); and- The Phase 2 INVENT COVID trial in the Netherlands evaluating Gleevec in patients with COVID-19 requiring mechanical ventilation (NCT04794088).

Last Update : 8/13/2021

Medication Class : Serine protease inhibitor

Trade Name : Foipan/Foistar/DWJ1248 (camostat mesilate)

Developer Researcher : Ono Pharmaceutical

Sponsors : Various

Trial Phase : Phase 2/3

Details : Background: Foipan, Foistar, or DWJ1248 (generic name: camostat mesilate) is an inhibitor of the enzyme transmembrane protease, serine 2 (TMPRSS2) being investigated in several trials as a therapeutic against COVID-19. Some in vitro studies suggested Foipan may prevent infection of SARS-CoV and may provide protection against SARS-CoV-2. Trials: Key COVID-19 trials for Foipan include: - A Phase 2 study of COVID-19 outpatients (NCT04353284), and a Phase 1/2 trial of patients with SARS-COV-2 associated coagulopathy at Yale University (NCT04435015). - The Phase 2 CAMELOT study of COVID-19 outpatients sponsored by Sagent Pharmaceuticals (NCT04583592). - The Phase 3 CAMOVID study at Hôpitaux de Paris of ambulatory patients with COVID-19 (NCT04608266). - The Phase 2 COPPS (NCT04662086)(NCT04662073) trial of non-hospitalized patients with COVID-19, and the Phase 2 COPS-2002 study of mild-to-moderate COVID-19 patients at Stanford University (NCT04524663). - A Phase 2 trial of ambulatory COVID-19 patients at University Hospital, Ghent in Belgium (NCT04625114). - A Phase 2/3 trial of patients with COVID-19 in the United Kingdom using Foipan at home as an intervention to prevent disease progression (NCT04455815). - A Phase 3 study of patients with COVID-19 receiving oral tablets sponsored by Ono Pharmaceutical (NCT04657497). - The Phase 3 DAWN trial of ambulatory COVID-19 patients in Belgium (NCT04730206). - A treatment arm of the Phase 2 RES-Q-HR trial from the Federal Ministry of Health in Germany (NCT04681430). - The Phase 1/2 CamoCO-19 trial in patients either hospitalized or outpatient with COVID-19 at the University of Aarhus (NCT04321096). - The Phase 2 RECOVER trial at the Mayo Clinic of patients hospitalized with COVID-19 (NCT04470544). - A treatment arm of a substudy in the ACTIV-2 trial (NCT04518410).- Daewoong Pharmaceutical is evaluating Foipan (as DWJ1248) in a Phase 2 trial of patients with mild/moderate COVID-19 (NCT04521296), a Phase 3 trial together with Veklury in patients with severe COVID-19 (NCT04713176), and a Phase 3 trial as a preventative treatment after exposure to COVID-19 (NCT04721535).Outcomes: Results from the Phase 1/2 CamoCO-19 trial, published in EClinicalMedicine, showed camostat mesilate was not effective at improving median time to clinical improvement or mortality compared with placebo. In a press release, Ono Pharmaceutical said results from their Phase 3 trial showed oral Foipan tablets did not result in faster time to a negative COVID-19 test. In the Phase 2b trial of patients with mild COVID-19 sponsored by Daewoong Pharmaceutical, Foipan improved recovery of clinical symptoms such as cough and dyspnea by 40% overall and by 50% for participants over 50 years of age compared with placebo, according to a press release.Status: Based on their Phase 3 study's results, Ono Pharmaceutical announced they would be discontinuing development of oral Foipan as a COVID-19 therapeutic candidate.

Last Update : 8/13/2021

Medication Class : Monoclonal antibody

Trade Name : Bamlanivimab (LY-CoV555)

Developer Researcher : Lilly,AbCellera

Sponsors : Lilly,Operation Warp Speed

Trial Phase : No longer being developed for COVID-19

Details : Background: Bamlanivimab is a monoclonal antibody that binds to the spike protein receptor in SARS-CoV-2 and can block viruses from binding to the ACE2 host cell surface receptor. The monoclonal antibody has been shown to protect against SARS-CoV-2 in non-human primates, according to a paper published in Science Translational Medicine.Regulatory Actions: On 9 November, the FDA issued an EUA for bamlanivimab, injection, 700 mg/20 mL, for use in adults and adolescents 12 years and older with mild or moderate COVID-19 at high risk for progressing to severe COVID-19 and/or hospitalization. Authorization was based on results from BLAZE-1, where the authorized dose did not significantly reduce viral load. Due to a lack of efficacy for bamlanivimab alone against SARS-CoV-2 variants, the FDA finally revoked the EUA on 16 April. Lilly said it had requested the action due to the "evolving variant landscape in the US and the full availability of bamlanivimab and etesevimab together." EMA noted on 5 March that despite uncertainties, bamlanivimab alone "can be considered a treatment option." On 20 November, Health Canada issued an interim authorization for bamlanivimab based on the data from BLAZE-1. Bamlanivimab was given a favorable recommendation for approval by the Committee for New Molecules in Mexico on 16 March.Trials: Key trials include:- BLAZE-1 (NCT04427501), a Phase 2 study of 800 patients with mild to moderate COVID-19 receiving bamlanivimab alone or in combination with etesevimab.- BLAZE-2 (NCT04497987), a Phase 3 study of long-term care residents with COVID-19 being conducted with NIAID.- BLAZE-4 (NCT04634409), a trial of patients with mild or moderate COVID-19 receiving bamlanivimab alone, together with etesevimab (JS016), or placebo. BLAZE-4 has been expanded to also include VIR-7831 from Vir Biotechnology/GSK.- ACTIV-2: (NCT04518410), a trial of patients with symptoms of COVID-19 who have not been hospitalized.- ACTIV-3 (NCT04501978), a trial of patients receiving bamlanivimab in combination with Veklury for hospitalized patients.- A Lilly executive told Reuters that bamlanivimab and etesevimab are being evaluated in a trial against the B.1.351 variant of SARS-CoV-2 originating in South Africa.- A Phase 1 trial (NCT04411628) of 24 patients hospitalized with COVID-19 who received bamlanivimab or placebo was completed.Outcomes:- BLAZE-1: An interim analysis of BLAZE-1 published in NEJM showed the 2800 mg dose significantly reduced (P = 0.02) viral load by day 11, while the other two doses did not significantly do so (700 mg dose, P = 0.38; 7000 mg dose, P = 0.70). Further data from 1,035 patients in BLAZE-1 announced by Lilly in a press release on 26 January showed a significant reduction in COVID-19 related hospitalizations and deaths in the intervention group compared with placebo (P = .0004).- BLAZE-2: Eli Lilly announced BLAZE-2 results by press release on 21 January, which showed a significantly lower rate of symptomatic COVID-19 in patients receiving bamlanivimab compared with placebo (odds ratio, 0.43, P = .00021), and a significantly lower rate of symptomatic COVID-19 in a subgroup of nursing home residents receiving bamlanivimab compared with the placebo group (odds ratio, 0.20; P = .00026).- BLAZE-4: In a press release, Lilly shared initial results that showed lower doses of both bamlanivimab and etesevimab had similar viral load and pharmacodynamic/pharmacokinetic data compared with higher doses of the combination of drugs. On 29 March, Lilly, Vir and GSK announced patients who received bamlanivimab (700 mg) together with VIR-7831 (500 mg) had a 70% reduction in viral load at 7 days compared with a placebo group.- ACTIV-3: Results from ACTIV-3, published in NEJM, showed bamlanivimab together with Veklury was not significantly more effective than placebo at improving clinical outcomes for COVID-19.- B.1.351 variant: In a pre-print posted to bioRxiv of results from a study by researchers at Columbia University, bamlanivimab had a "completely or markedly abolished" antibody response to the B.1.351 variant of SARS-CoV-2.- Prevention of hospitalization: A small matched cohort study found bamlanivimab infusion in patients with mild or moderate COVID-19 significantly reduced hospitalizations, returns to the emergency department, and death compared with placebo. The results were published in the journal Pharmacotherapy.Status: On 26 October, NIH closed the ACTIV-3 trial due to lack of efficacy. In updated treatment guidelines issued 8 April, NIH recommended use of bamlanivimab/etesevimab for "outpatients with mild to moderate COVID-19 who are at high risk of clinical progression" but recommended against bamlanivimab monotherapy, citing evidence of reduced effectiveness against SARS-CoV-2 variants.

Last Update : 8/2/2021

Medication Class : Monoclonal antibody

Trade Name : Ilaris (canakinumab)

Developer Researcher : Novartis

Sponsors : Novartis

Trial Phase : Phase 3

Details : Background: Ilaris (canakinumab) is a monoclonal antibody that targets interleukin (IL)-1β. Two studies published in The Lancet of COVID-19 showed patients had elevated levels of IL-1β and other cytokines during cytokine release syndrome. It is approved to treat cryopyrin-associated periodic syndromes (FDA, European Medicines Agency); tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and familial Mediterranean fever (FDA).Trials: Novartis conducted the international Phase 3 CAN-COVID trial (NCT04362813) to evaluate Ilaris vs. placebo for hospitalized COVID-19 patients with cytokine release syndrome. In the Phase 2 Canakinumab in Covid-19 Cardiac Injury (The Three C Study), Ilaris did not significantly improve outcomes at doses of 300 mg or 600 mg in hospitalized patients with COVID-19 and evidence of cardiac injury, according to results presented 13 November at the American Heart Association Virtual Scientific Sessions (NCT04365153). Both trials are active but not recruiting. Outcomes: CAN-COVID trial results, published in JAMA, showed that Ilaris did not significantly increase survival rates without the aid of invasive mechanical ventilation compared with a placebo group (88.8% vs. 85.7%). A retrospective review of 10 patients published in The Lancet found that Ilaris reduced serum C-reactive protein early in treatment (day 1 and day 3) and improved oxygenation at day 3 and day 7. At 45 days post-hospitalization, no patients had died and all had been discharged. Results from a small study published in Immunity, Inflammation, and Disease showed patients who received Ilaris had reduced inflammation and improved oxygen, with 60.3% of patients experiencing improvement in symptoms.

Last Update : 8/2/2021

Medication Class : Antihelmintic

Trade Name : Ivermectin

Developer Researcher : Various

Sponsors : Various

Trial Phase : Phase 2/3

Details : Background: Ivermectin is used in humans to treat intestinal strongyloidiasis and onchocerciasis (tablets), lice and rosacea (topical). The drug inhibited replication of SARS-CoV-2 in vitro within 48 hours of treatment, according to a paper published in Antiviral Research. It has also shown potential when delivered as a nasal spray in a pig model.Regulatory Actions: Ivermectin has been allowed for use in Zimbabwe by the Medicines Control Authority of Zimbabwe under a stringent framework.Trials: Ivermectin is being tested in dozens of clinical trials worldwide. The following is a list of randomized, placebo-controlled trials evaluating it:- A treatment arm of the ACTIV-6 (NCT04885530).- CES University: A small Phase 2 trial in Colombia is evaluating ivermectin's effect on patients with severe COVID-19 (NCT04602507).- CORVETTE-01: A Phase 2 outpatient trial in Japan (NCT04703205).- COVidIVERmectin: IRCCS Sacro Cuore Don Calabria di Negrar is testing ivermectin in a Phase 2 trial in Brazil (NCT04438850).- EPIC: A double-blind, randomized single-site trial in Colombia that found adults with mild COVID who received 300 mcg/kg of body weight of ivermectin for 5 days saw no significant improvement in time to symptom resolution, compared to those on placebo. Results were published in JAMA (NCT04405843).- IFORS: The Phase 2 IFORS trial in Brazil (NCT04431466)- IVERCOL: A Phase 2/3 trial in Colombia is evaluating ivermectin in patients with severe COVID-19 (NCT04886362)- IVERCORCOVID19: Ivermectin is being evaluated against placebo in patients with COVID-19 in the Phase 2/3 IVERCORCOVID19 trial in Argentina (NCT04529525).- IVER-Leve: Non-peer-reviewed results posted to medRxiv showed ivermectin slightly reduced symptoms in outpatients treated with 24 mg every 7 days for 4 weeks. The trial was sponsored by the Ministry of Health in Argentina (NCT04784481).- IVERNEX-TUC: A Phase 2/3 trial sponsored by the Ministry of Health in Argentina tested ivermectin as a prophylactic in cases where participants are in close contact with an individual with confirmed COVID-19 (NCT04894721).- Laboratorio Elea Phoenix S.A.: Another small Phase 2 trial in Argentina evaluated ivermectin plus standard of care against standard of care alone. (NCT04381884).- Mansoura University: An inhaled form of ivermectin is being tested in a small Phase 3 trial in Egypt (NCT04681053).- MedinCell: A small Phase 1 trial evaluated the safety and tolerability of ivermectin over a 28-day period (NCT04632706).- PRINCIPLE: Ivermectin is being investigated in a treatment arm of the PRINCIPLE trial in the UK alongside favipiravir.- SAINT: A small Phase 2 trial in Spain of 24 patients with non-severe COVID-19 and no risk factors for severe disease. Patients were randomized to one 400 mcg/kg dose of ivermectin within 3 days of symptom onset or placebo. There was no difference in the proportion of PCR positives between the groups; however, there was a "marked reduction of self-reported anosmia/hyposmia, a reduction of cough, and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials," the investigators wrote in results published in The Lancet's EClinical Medicine (NCT04390022).- SAINTBO: A Phase 2 trial sponsored by the Universidad Mayor de San Simón in Bolivia is testing ivermectin in patients recently diagnosed with COVID-19 (NCT04836299).- SAINT-PERU: A Phase 2a trial in Peru is evaluating ivermectin as a treatment for COVID-19 with an outcome of a negative nasopharyngeal PCR test (NCT04635943).- Tanta University: An ivermectin nasal spray is being tested in a small Phase 2 trial in Egypt (NCT04510233) Tanta University is also testing ivermectin in a Phase 2/3 trial (NCT04403555), and in larger doses in a different Phase 2/3 trial (NCT04351347).- Temple University: A Phase 3 outpatient study (NCT04530474) has been planned Temple University in Philadelphia. This trial was withdrawn from ClinicalTrials.gov after publication of the 31 March WHO report. - Universidad Nacional de Asunción: A Phase 3, placebo-controlled trial of ivermectin is being conducted in Paraguay for patients with outpatient, non-severe COVID-19 (NCT04834115).- Zagazig University: In Egypt, a small Phase 2/3 trial is being sponsored by Zagazig University where patients with COVID-19 will receive either ivermectin or standard of care (NCT04445311).Outcomes: Evidence showing some benefit:- In a case-control study of ivermectin, hydroxychloroquine, and vitamin C as potential COVID-19 prophylactics published in PLOS One, researchers found a 73% reduction in COVID-19 infection over the following month among health care workers who received two ivermectin doses of 300 μg/kg 72 hours apart. No significant reduction in infections was seen for hydroxychloroquine or vitamin C. - A meta-analysis of ivermectin as a COVID-19 treatment, published in Open Forum Infectious Diseases, found the treatment reduced mortality by 56% across 11 randomized trials; however, the analysis has drawn criticism due to including unpublished studies and trials without a placebo group.  Evidence showing mixed benefit:- A Cochrane review of the evidence for ivermectin, published in July 2021, concluded that ivermectin's safety and efficacy are uncertain given the available evidence.- In a study published in the International Journal of Infectious Diseases, researchers at ICDDR in Bangladesh found patients with COVID-19 who received a 5-day course of ivermectin had significantly better viral clearance compared with patients taking placebo (P = .02), but patients who received ivermectin plus doxycycline did not perform significantly better than placebo. - MedinCell announced in December that it has presented the results from a Phase 1 trial of subcutaneous ivermectin as a kind of pre-exposure prophylaxis for SARS-CoV-2 a collaborative workshop. The company noted no side effects were noted after two of three doses and that a "long-acting injectable formulation is ready to enter regulatory development."  Evidence showing no benefit:- Results from a study of 476 adults with mild COVID-19 in Colombia published in JAMA showed a 5-day course of ivermectin did not significantly improve time to resolution of symptoms compared with placebo.- EPIC: Ivermectin did not significantly reduce the time to symptom resolution in the now-completed Phase 2/3 EPIC trial in Colombia, according to local news reports. - IVERCOR-COVID19: There was no significant difference between ivermectin and placebo regarding hospitalization rates, according to a paper published in BMC Infectious Diseases.- SAINT: There was no difference in the proportion of positive SARS-CoV-2 PCR tests 7 days after treatment with ivermectin vs. placebo in the Phase 2 SAINT trial of 24 patients conducted in Spain, according to data published in EClinicalMedicine.Status: Since being identified as a potential COVID-19 treatment candidate, regulatory authorities and health agencies have made statements supporting or recommending against using ivermectin in patients with COVID-19:- Africa CDC: Africa Centres for Disease Control and Prevention (Africa CDC) has stated there is currently no evidence supporting its use but will monitor studies assessing the safety and efficacy of ivermectin.- EMA: On 23 March, the EMA advised against using ivermectin outside a clinical trial setting as a COVID-19 treatment.- FDA: FDA has warned consumers not to use ivermectin to treat or prevent COVID-19.- IDSA: The Infectious Diseases Society of America recommends against using ivermectin in hospitalized and outpatient cases of COVID-19.- NIH: NIH's COVID-19 Treatment Guidelines Panel guidance updated 11 February note there is “insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19,” recommending more well-designed, adequately-powered studies for further guidance.- South Africa: South Africa has allowed the use of ivermectin to treat COVID-19 under a compassionate use program since 27 January; the country reaffirmed that status on 3 February.- WHO: On 31 March, WHO added a recommendation to their guidelines on COVID-19 treatment that ivermectin should be used only in the clinical trial setting.

Last Update : 8/2/2021

Medication Class : immunomodulatory antibody

Trade Name : Mupadolimab (CPI-006)

Developer Researcher : Corvus Pharmaceuticals, Inc.

Sponsors : Corvus Pharmaceuticals, Inc.

Trial Phase : No longer being studied for COVID-19

Details : Background: Corvus Pharmaceuticals is evaluating whether mupadolimab (formerly CPI-006), an immunomodulatory antibody, is an effective therapy for patients with COVID-19. Trials: Mupadolimab was examined in two clinical trials: a Phase 1 trial of up to 70 patients hospitalized with COVID-19 compared with standard of care (NCT04464395), and a Phase 3 trial of up to 1,000 participants in combination with standard of care compared to a placebo group (NCT04734873). Outcomes: Results from the Phase 1 trial, presented as an oral presentation and a poster at the Society for Immunotherapy of Cancer meeting in 2020 and in a pre-print posted to medRxiv, indicated the treatment reduces median time to discharge for hospitalized patients, with no patients progressing to mechanical ventilation.Status: On 15 July, Corvus announced it is discontinuing the Phase 3 trial for mupadolimab due to the success of COVID-19 vaccines in lowering the risk of severe disease and hospitalization, but will continue to study the therapy in oncology.

Last Update : 6/25/2021

Medication Class : Anticoagulant

Trade Name : Eliquis (Apixaban)

Developer Researcher : NHLBI

Sponsors : Operation Warp Speed

Trial Phase : Phase 3/4

Details : Background: Eliquis (apixaban) is an anticoagulant being evaluated in several high-profile trials as a COVID-19 treatment candidate. Trials: - ACTIV-4: Researchers from NIH have launched NIH ACTIV-4 Outpatient trial, which will evaluate if anticoagulants or antithrombotic therapy has an effect on reducing cardiovascular or pulmonary complications that develop as a result of COVID-19. In the Phase 3 ACTIV-4 Outpatient trial, participants will be randomized to receive the anticoagulant apixaban, aspirin, or a placebo (NCT04498273).- ACTIV4c: A Phase 3 trial sponsored by the National Heart, Lung, and Blood Institute examining post-hospital thromboprophylaxis outcomes for patients with COVID-19 (NCT04650087). - HEAL-COVID-19: Apixaban is also being evaluated as a treatment for patients with consequences of COVID-19 in the HEAL-COVID-19 trial in the UK against atorvastatin (NCT04801940).- APOLLO: The Brazilian Clinical Research Institute is evaluating apixaban as a prophylactic for patients with COVID-19 and risk factors for thrombosis (NCT04746339).- FREEDOM COVID: A Phase 4 trial at Mount Sinai evaluating apixaban and the anticoagulant enoxaparin in up to 3,600 participants with COVID-19 who are hospitalized but not intubated (NCT04512079).Status: On 21 June, Brigham and Women's Hospital announced a data and safety monitoring board in the ACTIV-4b COVID-19 Outpatient trial recommended the trial be ended due to a low rate of cardio-pulmonary complications, which "do[es] not justify antithrombotic therapy." The trial has stopped enrolling, but follow-up is continuing.

Last Update : 6/25/2021

Medication Class : Antiviral

Trade Name : Avigan (favilavir/avifavir)

Developer Researcher : Fujifilm Toyama Chemical (as Avigan),Zhejiang Hisun Pharmaceutical

Sponsors : Various

Trial Phase : Phase 2/3

Details : Background: Reports from officials in China have said Avigan is clinically effective against COVID-19. Regulatory Actions: Avigan is approved in Italy to treat COVID-19, and in China as an experimental drug for COVID-19. Avifavir, a generic form of Avigan, has been approved to treat COVID-19 in Russia. Trials: Avigan is being evaluated in a number of high-profile clinical trials:- In the US, Appili Therapeutics is evaluating Avigan in the Prevent Severe COVID-19 (PRESECO) Study (NCT04600895), and as chemoprophylaxis in long-term care facilities (NCT04448119).- In Canada, Appili Therapeutics announced they are conducting a Phase 2 trial of favilavir with 760 participants (residents and staff) in long-term care facilities.- In the US, Fujifilm is evaluating Avigan in patients hospitalized with COVID-19 in a Phase 2 trial (NCT04358549).- In the UK, Fujifilm is collaborating with Chelsea and Westminster NHS Foundation Trust and Imperial College London to investigate Avigan's use in early intervention for COVID-19 in the Phase 3 PIONEER trial (NCT04373733).- PRINCIPLE: Also in the UK, favipiravir is being tested as a COVID-19 therapeutic alongside ivermectin in the PRINCIPLE trial.- Fujifilm announced a Phase 3 clinical trial to evaluate the safety and efficacy of Avigan in Japan for patients of COVID-19 in March 2020, but is starting a new trial in April 2021 to address concerns from Japanese regulators.- A Phase 2, placebo-controlled trial sponsored by Stanford University of oral Avigan in patients with mild disease (NCT04346628).- The adaptive Phase 2 VIRCO trial at Bayside Health in Australia (NCT04445467).- The Phase 2 FLARE trial sponsored by University College London investigating Avigan, Kaletra, or placebo (NCT04499677).- A Phase 2/3 trial at King Abdullah International Medical Research Center in Saudi Arabia (NCT04464408)- Dr. Reddy's Laboratories also evaluated Avigan in patients hospitalized with moderate-to-severe COVID-19 against placebo in a Phase 3 trial in Kuwait (NCT04529499). - A Phase 3 trial in Nepal of patients with mild or moderate COVID-19 comparing Avigan, Veklury, and placebo (NCT04694612).- A Phase 3 trial of patients with moderate COVID-19 sponsored by Zhejiang Hisun Pharmaceutical Co. Ltd. (NCT04425460).- In Russia, a 330-person Phase 3 trial of avifavir in patients hospitalized with COVID-19 is ongoing (NCT04434248), a Phase 3 trial of patients with mild or moderate COVID-19 sponsored by R-Pharm is active, but not recruiting (NCT04501783), and a Phase 3 trial sponsored by Promomed, LLC has been completed (NCT04542694). - A randomized trial in the Philippines pitting Avigan against standard of care in four hospitals is also planned. Outcomes: Recent data appears to show lack of efficacy of Avigan in treating COVID-19. A study presented in the pre-print server medRxiv of 240 patients that evaluated favilavir against Arbidol (umifenovir, a broad-spectrum antiviral used for influenza) showed neither drug was more effective at improving the clinical recovery rate of patients. Interim data from Japan suggested the favilavir was not effective in treating mild or moderate cases of COVID-19, which was confirmed by a press release from researchers in Fujita Health University. A non-peer-reviewed systematic review and meta-analysis posted to medRxiv showed patients in the Avigan group experienced significant clinical improvement within 7 days after hospitalization but did not significantly improve the use of supplemental oxygen or mortality compared with the placebo group. Status: Trials have various dates of completion. On 27 January, Dr. Reddy's Laboratories announced they were ending their study in Kuwait, citing non-significant differences between patient groups; however, the company plans to continue the Phase 3 PRESECO Study in partnership with Appili Therapeutics. Fujifilm has sought approval of Avigan as a treatment for COVID-19 in Japan, but has run into concerns from Japanese regulators, such as Fujifilm's study design; the company aims to conduct a new clinical trial and reapply for approval in October.

Last Update : 6/18/2021

Medication Class : JAK inhibitor

Trade Name : Xeljanz (tofacitinib)

Developer Researcher : Pfizer, National Institutes of Health

Sponsors : Various

Trial Phase : Phase 2

Details : Background: Xeljanz (tofacitinib) is a Janus kinase (JAK) inhibitor approved in the US to treat rheumatoid arthritis and also used in psoriatic arthritis and ulcerative colitis. It is being evaluated as a therapeutic for COVID-19.Trials: Xeljanz is being tested as a treatment for moderate COVID-19 in the Phase 2 I-TOMIC trial at Yale University (NCT04415151), and for treating patients with pneumonia associated with COVID-19 in the Phase 2 STOP-COVID trial in Brazil in collaboration with Pfizer (NCT04469114), a Phase 2 trial at the Università Politecnica delle Marche in Italy (NCT04332042), and a Phase 2 trial at Sechenov First Moscow State Medical University in Russia, which has been completed (NCT04750317).Outcomes: According to results from the STOP-COVID trial, published in NEJM, 18.1% of patients with COVID-19 who received tofacitinib experienced respiratory failure or died by 28 days compared with 29.0% of patients who received a placebo (risk ratio, 0.63; 95% CI, 0.41-0.97; P = .04).

Last Update : 6/11/2021

Medication Class : Monoclonal antibodies

Trade Name : BMS-986414/BMS-986413

Developer Researcher : Rockefeller University,Bristol Myers Squibb,AIDS Clinical Trials Group

Sponsors : NIAID

Trial Phase : Phase 2/3

Details : Background: BMS-986414 and BMS-986413 are two monoclonal antibodies developed by Bristol Myers Squibb and Rockefeller University from patients who had recovered from COVID-19. The combination of both monoclonal antibodies are being evaluated as a therapeutic for COVID-19 in a treatment arm of the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial alongside other therapeutics (NCT04518410).

Last Update : 6/4/2021

Medication Class : Oral cytoskeleton disruptor

Trade Name : Sabizabulin (VERU-111)

Developer Researcher : Veru Inc.

Sponsors : Veru Inc.

Trial Phase : Phase 2/3

Details : Background: Veru Inc. is testing whether their oral first-in-class small molecule sabizabulin (VERU-111) is effective as a COVID-19 therapeutic.Trials: Sabizabulin is being evaluated in a Phase 2 study of 40 participants with COVID-19 and respiratory failure, which is currently active but not recruiting (NCT04388826). The candidate is also being tested in a Phase 3 trial launched by Veru, which is currently recruiting (NCT04842747).Outcomes: Phase 2 results announced by Veru in February 2021 through a press release showed patients who received sabizabulin had an 81% reduction in treatment failure compared with a placebo group (P = .05).

Last Update : 6/4/2021

Medication Class : Spleen tyrosine kinase inhibitor

Trade Name : Tavalisse (fostamatinib)

Developer Researcher : Rigel Pharmaceuticals, Inc

Sponsors : Rigel Pharmaceuticals, Inc,NHLBI,Imperial College London

Trial Phase : Phase 1/2/3

Details : Background: Rigel Pharmaceuticals is testing whether Tavalisse (fostamatinib), an oral chronic immune thrombocytopenia treatment, is a viable therapeutic for patients hospitalized with COVID-19. Trials: Together with the National Heart, Lung, and Blood Institute (NHLBI), Rigel Pharmaceuticals evaluated Tavalisse compared with placebo in a Phase 2 trial for up to 62 participants hospitalized with COVID-19 receiving standard of care (a steroid plus Veklury); this trial has been completed (NCT04579393). Rigel is also evaluating Tavalisse in a UK trial with the Imperial College Healthcare NHS Trust and Novartis in the Phase 1/2 MATIS trial for patients hospitalized with COVID-19, which is currently recruiting (NCT04581954). Additionally, Rigel is conducting a Phase 3 international trial of Tavalisse in patients with COVID-19 (NCT04629703).Outcomes: Results from the Phase 2 NHLBI trial were announced in April 2021 through a press release, where Rigel said Tavalisse reduced the primary outcome of incidence of severe adverse events compared with a placebo group (3 vs. 6 events) and specifically reduced the incidence of hypoxia compared with placebo (1 vs. 3 events); however, neither result was statistically significant. Rigel noted that the Tavalisse group had no deaths at the end of 29 days compared with 3 deaths in the placebo group (P = .07), and there was an accelerated improvement in clinical status for patients receiving Tavalisse compared with placebo that was significant at 15 days (mean change -3.6 vs. -2.6; P = .035) but not 29 days (mean change -4.2 vs. -3.3; P = .12).Status: Based on results from their Phase 2 trial, Rigel said they plan to apply for an emergency use authorization (EUA) with the FDA for patients hospitalized with COVID-19.

Last Update : 5/21/2021

Medication Class : Oral sodium-glucose co-transporter 2 (SGLT2) inhibitor

Trade Name : Farxiga (dapagliflozin)

Developer Researcher : Bristol-Myers Squibb

Sponsors : AstraZeneca

Trial Phase : Phase 3

Details : Background: Farxiga is primarily used to treat type 2 diabetes by promoting glucosuria. In the DECLARE CV trial, the drug was associated with a lower rate of heart failure resulting in hospitalization and cardiovascular death. Other trials have shown Farxiga also has kidney-protective effects. Farxiga is used to treat type 2 diabetes and heart failure with reduced ejection fraction. Trials: AstraZeneca is evaluating Farxiga in the Phase 3 DARE-19 trial of 900 participants with COVID-19 and comorbid conditions such as hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 chronic kidney disease (NCT04350593).Status: On 12 April, AstraZeneca announced high-level results from DARE-19, which showed that Farxiga did not significantly prevent 30-day "organ dysfunction and all-cause mortality, and the primary endpoint of recovery measuring a change in clinical status" compared with placebo. These results were confirmed through data presented at the annual meeting of the American College of Cardiology, which showed 11.2% of patients receiving Farxiga had organ failure or died after 30 days compared with 13.8% in the placebo group.

Last Update : 5/21/2021

Medication Class : rhACE2

Trade Name : APN01

Developer Researcher : Apeiron Biologics

Sponsors : Apeiron Biologics

Trial Phase : Phase 2

Details : Background: APN01 is a recombinant human angiotensin-converting enzyme 2 (rhACE2) developed by Apeiron Biologics. It is a soluble recombinant version of ACE2 that blocks ACE2 receptors. Trials: APN01 is being evaluated in patients with COVID-19 in a Phase 2 trial in Germany, Austria, Denmark, the UK, and Russia of approximately 100 participants (NCT04335136). APN01 also has been selected to be a treatment arm in the ACTIV-4d trial. Outcomes: Topline results from Apeiron's Phase 2 trial, announced in March 2021, showed the candidate was safe and well-tolerated.

Last Update : 5/21/2021

Medication Class : AT1 receptor selective agonist

Trade Name : TRV027

Developer Researcher : Trevena

Sponsors : Various

Trial Phase : Phase 1/4

Details : Background: TRV027, an AT1 receptor-selective agonist developed by Trevena in conjunction with Imperial College London, is being evaluated in several trials as a potential therapeutic candidate for COVID-19.Trial: TRV027 is being tested in a treatment arm of the REMAP-CAP trial (NCT02735707), as a treatment arm of the ACTIV-4d trial led by Vanderbilt University Medical Center, and in an early Phase 1 trial in hospitalized COVID patients (NCT04419610).

Last Update : 5/14/2021

Medication Class : Angiotensin-(1–7) peptide

Trade Name : TXA127

Developer Researcher : Constant Therapeutics

Sponsors : Columbia University Irving Medical Center

Trial Phase : Phase 2

Details : Background: Constant Therapeutics is testing its peptide angiotensin-(1-7) drug TXA127 in a Phase 2 clinical trial. The peptide is a Mas receptor agonist which has demonstrated efficacy in reducing inflammation, stabilizing endothelial and epithelial barriers, and reducing fibrosis in the lungs of animal models. Study Design: A randomized, parallel, double-blinded, placebo-control, Phase 2 trial of 100 patients with moderate COVID-19 (NCT04401423). TXA127 is also being evaluated as a treatment in the ACTIV-4d trial, according to a press release from Constant Therapeutics.

Last Update : 5/14/2021

Medication Class : Monoclonal antibody

Trade Name : VIR-7832 (GSK4182137)

Developer Researcher : Vir Biotechnology, Inc.,GSK

Sponsors : Vir Biotechnology, Inc.

Trial Phase : Phase 1b/2a

Details : Background: Vir Biotechnology, Inc. and GlaxoSmithKline are evaluating their monoclonal antibody VIR-7832 (GSK4182137) to treat COVID-19. VIR-7832 has shown the ability to neutralize SARS-CoV-2 in vitro, according to the companies.Trials: VIR-7832 is being evaluated in the Phase 1b/2a AGILE study as a treatment for patients with mild-to-moderate COVID-19; in AGILE, VIR-7832 will be tested for safety and tolerability in the Phase 1b portion of the study and then compared with VIR-7831, another monoclonal antibody developed by Vir and GSK, and placebo in the Phase 2a portion of the study. AGILE is currently underway (NCT04746183).

Last Update : 5/7/2021

Medication Class : Antiviral

Trade Name : Carragelose, Nasitrol (carrageenan nasal spray)

Developer Researcher : Marinomed Biotech AG

Sponsors : Marinomed Biotech AG,Various

Trial Phase : Phase 4

Details : Background: Carrageenan nasal spray is being investigated as a prophylactic for preventing COVID-19. It has been shown to inhibit SARS-CoV-2 in vitro in several pre-print papers. Trials: Carragelose as a brand name and as an iota-carrageenan nasal spray are being evaluated in a number of clinical trials:- The ICE-COVID trial sponsored by Swansea University is evaluating carrageenan nasal spray under the brand name Nasitrol as prophylaxis for COVID-19 among ICU staff (NCT04590365);- The Phase 4 CARR-COV-02 trial in Argentina as a prophylactic for healthcare workers (NCT04521322); - In Austria as a prophylactic to prevent infection in healthcare workers (NCT04681001) and in hospitalized patients with COVID-19 (NCT04793984) in trials sponsored by Marinomed Biotech AG. Outcomes: Preliminary results from a non-peer-reviewed pre-print of 394 participants in the CARR-COV-02 trial show that 1.0% of the 199 participants who received the nasal spray developed COVID-19 compared with 5.1% of 195 participants in the placebo group (relative risk reduction, 80.4%; 95% confidence interval, 25-95%; P = .01), with similar rates of adverse events between groups. In a press release on 21 April, Marinomed Biotech announced that Carragelose was able to inactivate B.1.1.7, B.1.351 and P.1, and wild-type SARS-CoV-2 in in vitro tests. In the ICE-COVID trial, there was a significantly lower incidence of COVID-19 in the group of ICU staff who received Nasitrol compared with placebo, according to a press release.

Last Update : 5/7/2021

Medication Class : Glycoprotein receptor binding domain-specific antibody

Trade Name : LY-CoV1404

Developer Researcher : AbCellera Biologics Inc.,Eli Lilly

Sponsors : Eli Lilly

Trial Phase : Phase 2

Details : Background: Eli Lilly and Company are testing whether LY-CoV1404, a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody, is a viable a therapeutic for patients with COVID-19. The antibody was discovered by AbCellera Biologics. Preclinical testing of LY-CoV1404 has shown neutralizing activity against the original SARS-CoV-2 virus as well as several new variants, such as B.1.1.7, B.1.351, B.1.427/B.1.429, P.1, and B.1.526.Trial: LY-CoV1404 is being evaluated as a treatment arm in the BLAZE-4 trial in patients with mild or moderate COVID-190 (NCT04634409).

Last Update : 4/23/2021

Medication Class : Antiviral

Trade Name : NT-300 (nitazoxanide extended-release)

Developer Researcher : Romark Laboratories L.C.

Sponsors : Romark Laboratories L.C.

Trial Phase : Phase 3

Details : Background: NT-300, an antiviral developed by Romark Laboratories L.C., is being evaluated as a therapeutic candidate for COVID-19.Trials: Romark is testing NT-300 in a Phase 3 placebo-controlled trial of up to 1,092 participants with mild to moderate COVID-19 (NCT04486313). Additionally, Romark is evaluating NT-300 in a Phase 3 trial as a pre-exposure and post-exposure prophylactic for COVID-19 and other viral respiratory illnesses in healthcare workers (NCT04359680) and in long-term care facilities (NCT04343248).Outcomes: Initial results from the Phase 3 trial of mild-to-moderate COVID-19, announced by press release, show an 85% reduction of progression to severe COVID-19 among participants who received NT-300 compared with placebo. Status: Based on positive results from their Phase 3 trial, Romark indicated it would seek emergency use authorization (EUA) for NT-300 with the FDA.

Last Update : 4/23/2021

Medication Class : Polyclonal antibody

Trade Name : SAB-185

Developer Researcher : SAb Biotherapeutics

Sponsors : NIAID

Trial Phase : Phase 2/3

Details : Background: SAB-185, a polyclonal antibody developed SAb Biotherapeutics, Inc., is being evaluated as a potential therapeutic for patients with mild to moderate COVID-19.Trials: A Phase 1 safety and efficacy trial enrolled 21 patients (NCT04469179). NIAID is evaluating SAB-185 as a treatment arm in their Phase 2/3 ACTIV-2 trial of patients with COVID-19 that are not currently hospitalized (NCT04518410). The company announced on 21 April that the first patient had received the treatment. 

Last Update : 4/23/2021

Medication Class : Monoclonal antibodies

Trade Name : C135-LS/C144-LS

Developer Researcher : The Rockefeller University/Bristol Myers Squibb

Sponsors : NIAID

Trial Phase : Phase 2/3

Details : Background: C135-LS/C144-LS, two monoclonal antibodies developed by The Rockefeller University and licensed by Bristol Myers Squibb, are being evaluated as a potential therapeutic for COVID-19.Trial: A Phase 1 dose-escalation study to assess safety and efficacy recruited 23 participants (NCT04700163). NIAID is evaluating C135-LS/C144-LS as a treatment arm in their Phase 2/3 ACTIV-2 trial of patients with COVID-19 that are not currently hospitalized (NCT04518410).

Last Update : 4/16/2021

Medication Class : Monoclonal antibody

Trade Name : Mavrilimumab

Developer Researcher : Kiniksa Pharmaceuticals

Sponsors : The Cleveland Clinic

Trial Phase : Phase 2

Details : Background: The potential treatment is designed to antagonize GM-CSF signaling by binding to the alpha subunit of the GM-CSF receptor (GM-CSFRα). Kiniksa’s lead indication for mavrilimumab is giant cell arteritis. Regulatory Actions: The FDA has approved an IND for a Phase 2/3 trial of mavrilimumab. Trials: Researchers at the Cleveland Clinic aim to recruit 60 participants in a prospective, Phase 2 trial evaluating early mavrilimumab treatment for respiratory failure in patients with COVID-19 (NCT04399980). At San Raffaele Hospital, researchers are evaluating mavrilimumab treatment response in the observational COVID-BioB study (NCT04318366). Kiniksa also is conducting an international Phase 2/3 trial of about 570 participants evaluating two dose levels of mavrilimumab for patients with COVID-19 and pneumonia (NCT04447469). Outcomes: Early reports of mavrilimumab showed early resolution of fever and improved oxygenation within one to three days without requiring mechanical ventilation, according to Kiniksa. - COVID-BioB study: Results from The Lancet show patients treated with mavrilimumab had better clinical outcomes compared with a control group at 28-day follow-up. - Cleveland Clinic: On 22 December, Kiniksa announced results from an investigator-initiated, placebo-controlled trial of mavrilimumab that showed the mavrilimumab group had a non-significant increase in the number of patients off of mechanical ventilation by 14 days and a non-significant increase in the number of patients who survived to 28 days without respiratory failure compared with placebo.- Phase 2/3 study: On 12 April, Kiniska announced results from a trial of patients with pneumonia and hyper-inflammation associated with COVID-19, which showed the proportion of patients who received mavrilimumab and survived to 29 days without requiring mechanical ventilation was 12.3 percentage points higher than the placebo group, there was a 65% reduction in mechanical ventilation and mortality, and a 61% reduction in mortality alone compared with the placebo group.

Last Update : 4/16/2021

Medication Class : Recombinant fusion protein

Trade Name : MK-7110 (CD24Fc/SACCOVID)

Developer Researcher : OncoImmune,Merck

Sponsors : OncoImmune,Merck

Trial Phase : No longer being studied for COVID-19

Details : Background: MK-7110 (formerly SACCOVID and CD24Fc) was part of several trials for the prophylactic treatment of graft-versus-host disease (GVHD) in leukemia patients receiving hematopoietic stem cell transplantation. The recombinant fusion protein targets a novel immune pathway checkpoint and modulates immune response through binding to Danger-Associated Molecular Patterns (DAMPS) and sialic acid-binding immunoglobulin-type lectins (Siglecs). The developers of MK-7110, OncoImmune, believe it can be an effective non-antiviral biological modifier in COVID-19 because it showed a reduction of multiple inflammatory cytokines in animal models. Trials: A Phase 3 trial of 230 COVID-19 patients with absolute lymphocyte counts ≤ 800/mm3 in peripheral blood has been completed (NCT04317040). Outcomes: Early results from the trial of the first 70 patients show no adverse reactions to infusion or drug-related adverse events. The 5% mortality rate in the trial was “low among severe and critical COVID-19 patients,” OncoImmune’s CEO said. Topline results announced by a press release from the company indicate MK-7110 helped reduce time to clinical recovery from 10 days in the placebo group to 6 days, and had “a 60% better chance to achieve clinical recovery” compared with placebo (P = .005), OncoImmune said. Status: Merck acquired OncoImmune in December 2020 and renamed the candidate to MK-7110. On 22 December, Merck announced it was partnering with Operation Warp Speed and would supply up to 100,000 doses of the therapeutic pending an EUA. On 25 January, Merck announced that the company was discontinuing its work on two candidate vaccines for COVID-19 to focus on MK-7110 and molnupiravir, another potential therapeutic. In a 10-k filing with the Securities and Exchange Commission on 25 February, Merck indicated it would not be able to meet its goal of supplying MK-7110 to the US government due to the FDA requiring more data to support an EUA application. On 15 April, Merck said it is discontinuing the development of MK-7110 as a COVID-19 candidate to focus on molnupiravir and producing COVID-19 Vaccine Janssen for Johnson & Johnson.

Last Update : 4/9/2021

Medication Class : Anthelmintic

Trade Name : Niclocide (niclosamide), UNI91103

Developer Researcher : NeuroBo Pharmaceuticals,UNION Therapeutics

Sponsors : Various

Trial Phase : Phase 2/3

Details : Background: Niclosamide, an antiparasitic drug used to manage tapeworm infections, is being investigated by several centers as a COVID-19 therapeutic. It has shown efficacy against SARS-CoV-2 in animal models. A proprietary capsule formulation called ANA-001 was developed by ANA Therapeutics (now owned by NeuroBo Pharmaceuticals). An intranasal formulation of niclosamide, UNI91103, has been developed by UNION Therapeutics. Trials: NeuroBo is evaluating ANA-001 under an IND issued by FDA in August 2020 (NCT04603924). Niclosamide is also being investigated in several other trials: - A randomized Phase 2 trial of 100 participants with mild-to-moderate COVID-19 at Tufts Medical Center (NCT04399356)- A Phase 2 trial of 100 participants with moderate COVID-19 sponsored by First Wave Bio, Inc. (NCT04436458) - A Phase 1 trial in South Korea sponsored by Daewoong Pharmaceutical (NCT04749173) - The Phase 2/3 PROTECT-V trial sponsored by the Cambridge University Hospitals NHS Foundation Trust, which is currently recruiting (NCT04389359)- The Phase 2 RESERVOIR trial, launched by AzurRx BioPharma, will evaluate an oral form of niclosamide named FW-1022.- A Phase 3 trial of niclosamide in combination with diltiazem against hydroxychloroquine and standard of care at Lille University Hospital in France (NCT04372082), which was withdrawn in March 2021 due to chloroquine's lack of efficacy.Status: On 29 March, the UK National Institute for Health Research (NIHR)  granted Urgent Public Health (UPH) prioritization to the PROTECT-V trial, according to a press release by UNION Therapeutics.

Last Update : 4/9/2021

Medication Class : Host defense protein (HDP) mimetic

Trade Name : Brilacidin (PMX-30063)

Developer Researcher : Innovation Pharmaceuticals

Sponsors : Innovation Pharmaceuticals

Trial Phase : Phase 2

Details : Background: Biopharmaceutical company Innovation Pharmaceuticals is evaluating whether their investigational new drug, brilacidin, is effective as a therapeutic for patients with COVID-19. Brilacidin has been described as an antiviral, anti-inflammatory and antibacterial drug, and has shown effectiveness in vitro against SARS-CoV-2, according to data posted on the BioRxiv, a pre-print server. Trial: A Phase 2 trial of 120 participants in the United States and internationally is currently underway (NCT04784897).Regulatory Actions: The FDA granted IND approval for brilacidin on 21 December, and Fast Track Designation on 14 January.

Last Update : 3/29/2021

Medication Class : Antirheumatic agent

Trade Name : Bucillamine

Developer Researcher : Revive Therapeutics Ltd.

Sponsors : Revive Therapeutics Ltd.

Trial Phase : Phase 3

Details : Background: Revive Therapeutics is testing antirheumatic drug bucillamine in a Phase 3 trial of patients with mild-to-moderate COVID-19. The trial is a randomized, placebo-controlled study of up to 1,000 participants who will receive bucillamine or placebo three times per day for up to 14 days. Study sites are currently listed in the US; the company notes it will expand location to Canada and Asia-Pacific countries (NCT04504734). The trial is listed as enrolling by invitation only. Status: Revive received IRB approval to move forward with the Phase 3 trial in August, and enrollment is currently underway, with plans to expand up to 50 clinical sites and an aim to apply for an emergency use authorization with the FDA. Bucillamine has also been granted compassionate use through IRB approval. On 24 March, Revive announced that there had been no serious adverse events or safety concerns so far in the trial.

Last Update : 3/12/2021

Medication Class : HIV-1 Rev protein inhibitor

Trade Name : ABX464

Developer Researcher : Abivax

Sponsors : Abivax

Trial Phase : Phase 2b/3

Details : Background: ABX464 has anti-inflammatory properties through its upregulation of miR-124 micro-RNA, which downregulates chemo- and cytokines causing cytokine release syndrome in patients with COVID-19. The candidate also has antiviral effects against HIV and has been effective in treating patients with ulcerative colitis. Trial: The company is conducting a Phase 2b/3 trial of 1,034 high-risk patients across 50 study sites in Europe and Latin America  (NCT04393038). Status: Results from the Phase 2b/3 miR-AGE trial, announced by press release, showed no difference in progression to severe disease in the ABX464 group compared with placebo. Based on these results and a recommendation from a Data Safety and Monitoring Board, Abivax has decided to stop the clinical trial.

Last Update : 2/19/2021

Medication Class : Biguanide

Trade Name : Metformin (Glucophage, Glumetza, Riomet)

Developer Researcher : University of Minnesota

Sponsors : University of Minnesota

Trial Phase : Phase 2/3

Details : Background: Metformin, an oral medication used to treat type 2 diabetes, is being evaluated as a therapeutic candidate for COVID-19. Early results from Wuhan, China, suggested metformin helped reduce the risk of mortality from COVID-19 in patients with type 2 diabetes. Trial: Researchers at the University of Minnesota are planning the Phase 2/3 MET-Covid trial with 1,522 participants to assess whether metformin is able to reduce COVID-19 severity, prevent symptomatic disease, and/or prevent SARS-CoV-2 infection (NCT04510194). Outcomes: In a retrospective study of 25,326 patients with COVID-19 published in Frontiers in Endocrinology, diabetes carried a significantly higher risk of mortality (odds ratio, 3.62; 95% confidence interval, 2.11-6.2; P < .0001), but metformin use in patients with diabetes was associated with a significant reduction in mortality from COVID-19 (OR, 0.33; 95 %CI, 0.13-0.84; P = .0210). Another study published in the Journal of the American Medical Directors Association of residents in nursing homes with diabetes found their metformin treatment reduced 30-day mortality from COVID-19. For women hospitalized with COVID-19 who also have type 2 diabetes and obesity, metformin was significantly associated with decreased mortality, but this association was not seen in men or in a sample of men and women, according to a study published in The Lancet Healthy Longevity. A meta-analysis of available studies evaluating COVID-19 published in Diabetes & Metabolism notes the potential of metformin in reducing mortality in patients with diabetes but cautions that randomized clinical trials are needed. In a propensity score-matched cohort study published in The Journal of Clinical Endocrinology & Metabolism, metformin did not appear to influence susceptibility for developing COVID-19 in patients with type 2 diabetes.

Last Update : 2/19/2021

Medication Class : Dihydroorotate dehydrogenase (DHODH) inhibitor

Trade Name : PTC299

Developer Researcher : PTC

Sponsors : PTC

Trial Phase : Phase 2/3

Details : Background: PTC has said PTC299 has the potential to address the high level of viral replication and inflammatory response associated with COVID-19. Results from a study published in Virus Research indicate the therapeutic is effective at inhibiting replication of SARS-CoV-2 and suppressed IL-6, IL-17A, IL-17F, and vascular endothelial growth factor in tissues cultures. Trials: A Phase 2/3 trial is underway to evaluate PTC299 in the US, which is currently in its second stage (NCT04439071). A Phase 2/3 in Australia has begun, and additional trials are planned in Europe and Brazil.

Last Update : 1/29/2021

Medication Class : Kinase inhibitor

Trade Name : Calquence (acalabrutinib)

Developer Researcher : AstraZeneca

Sponsors : AstraZeneca

Trial Phase : Phase 2

Details : Background: Calquence is indicated to treat mantle cell lymphoma (MCL) in patients who have received at least one prior therapy and to treat chronic lymphocytic leukemia (CLL) in the US. Calquence inhibits the enzyme Bruton’s tyrosine kinase (BTK). The BTK pathway has been implicated in TNF-alpha, IL-6, IL-10, and MCP-1 production and early data from the CALAVI trial has shown that Calquence is effective in reducing respiratory distress caused by COVID-19. Trials: CALAVI US (NCT04380688) and CALAVI (NCT04346199) enrolled at total of 225 hospitalized patients with COVID-19 and respiratory distress and randomized them 1:1 to Calquence plus best supportive care or best supportive care. Calquence is also being studied in a treatment arm of the SOLIDARITY trial (NCT04647669). Outcomes: The trials did not meet their primary efficacy endpoint, AstraZeneca announced 12 November 2020. Calquence, when added to best supportive care, did not reduce the proportion of deaths or respiratory failure in treated patients when compared to those receiving only best supportive care. An earlier study of 19 patients treated with Calquence published in the journal Science Immunology showed 8 of 11 patients (72.7%) requiring supplemental oxygen after being hospitalized for COVID-19 had their oxygenation improve to the point where they no longer required assistance, and 4 of 8 patients (50%) on mechanical ventilation had been extubated. C-reactive protein and IL-6 normalized in patients shortly after treatment. Status: CALAVI US is completed; CALAVI is listed as "active, not recruiting" on clinicaltrials.gov. 

Last Update : 1/29/2021

Medication Class : Monoclonal antibody

Trade Name : Etesevimab (LY-CoV016, JS016)

Developer Researcher : Lilly,Junshi Biosciences

Sponsors : Lilly

Trial Phase : Phase 1

Details : Background: Etesevimab (also known as LY-CoV016 or JS016) binds to the spike protein receptor in SARS-CoV-2 and can block viruses from binding to the ACE2 host cell surface receptor. Trials: Etesevimab is being evaluated in the following trials: - BLAZE-1 (NCT04427501), a Phase 2 study of 800 patients with mild to moderate COVID-19 receiving bamlanivimab alone or in combination with etesevimab. - BLAZE-2 (NCT04497987), a Phase 3 study of long-term care residents with COVID-19 being conducted with NIAID who will receive bamlanivimab alone or in combination with etesevimab. Lilly has announced a Phase 1 trial is underway evaluating etesevimab in 40 patients with COVID-19, and also is being evalauted in the Phase 2 BLAZE-1 study of 800 participants receiving LY-CoV555 or etesevimab as a combination therapy (NCT04427501). BLAZE-4: Additionally, it is being evaluated in the BLAZE-4 (NCT04634409) trial consisting of patients with mild or moderate COVID-19 receiving bamlanivimab alone, together with etesevimab, or placebo. BLAZE-4 has been expanded to also include Vir Biotechnology and GSK's VIR-7831. Status: Junshi Biosciences said bamlanivimab and etesevimab and met their primary endpoints in the BLAZE-1 trial. Lilly has submitted a request for an EUA for LY-CoV555 monotherapy based on results from the BLAZE-1 trial. In a press release, Lilly shared initial results that showed lower doses of both bamlanivimab and etesevimab had similar viral load and pharmacodynamic/pharmacokinetic data compared with higher doses of the combination of drugs.

Last Update : 1/22/2021

Medication Class : Anti-TNF

Trade Name : Humira (adalimumab)

Developer Researcher : University of Oxford,Pharm-Olam

Sponsors : COVID-19 Therapeutics Accelerator,Department of Defense

Trial Phase : Phase 2/2

Details : Background: Humira (adalimumab), an anti-tumor necrosis factor drug, is being evaluated in several trials as a therapeutic for COVID-19. Trials: The University of Oxford is testing whether Humira helps prevent the progression of COVID-19 to severe disease among patients in community care homes in the United Kingdom. The AVID-CC trial, sponsored by the COVID-19 Therapeutics Accelerator, is planning to enroll up to 750 patients with COVID-19 in care homes across the United Kingdom who will receive adalimumab or standard of care. Clinical research organization Pharm-Olam is working with the US Department of Defense to evaluate the drug in the Phase 2/3 Adalimumab COVID Therapeutic Trial. Humira is also being tested by Ology Bioservices in a Phase 3 trial of patients with mild or moderate COVID-19 (NCT04705844).

Last Update : 1/15/2021

Medication Class : Monoclonal antibody

Trade Name : Ultomiris (ravulizumab)

Developer Researcher : Alexion

Sponsors : Alexion

Trial Phase : Phase 3

Details : Background: Ultomiris is C5 complement inhibitor originally engineered from eculizumab to have a longer-lasting half-life and longer intervals between dosing for treatment of paroxysmal nocturnal hemoglobinuria. Preclinical data of animal models published in the open-access journal mBio suggested the treatment lowers cytokine and chemokine levels in viral pneumonia. Alexion said patients with COVID-19 accessing eculizumab through compassionate use programs also have shown some clinical benefit. Trials: Alexion is conducting a Phase 3 global study of 270 patients with COVID-19 hospitalized with severe pneumonia randomized to receive weight-based loading dose of Ultomiris followed by a weight-based dose on day 5 and day 10, and a 900-mg dose on day 15 (NCT04369469), which is currently recruiting. Regulatory Actions: The FDA has approved an IND for Ultomiris to treat patients with severe COVID-19, according to a company press release. Status: On 13 January, Alexion announced they were pausing enrollment in their trial due to lack of efficacy after a recommendation from an independent data monitoring committee.

Last Update : 1/8/2021

Medication Class : Monoclonal antibody

Trade Name : COVI-AMG/COVI-DROPS (STI-2020)

Developer Researcher : Sorrento Therapeutics

Sponsors : Sorrento Therapeutics

Trial Phase : Phase 1

Details : Background: Sorrento Therapeutics, Inc. is developing STI-1499, also called COVI-AMG, which is a neutralizing antibody that is the affinity matured version of Sorrento's COVI-GUARD therapeutic that binds to the S1 subunit of the spike protein in SARS-CoV-2. Pre-clinical research has shown effectivenessin protecting against SARS-CoV-2 in hamsters. Sorrento is also developing an intranasal formulation of COVI-AMG called COVI-DROPS. Trial: A Phase 1/2 trial of COVI-AMG has been approved by the FDA to proceed, but is not currently recruiting (NCT04584697).

Last Update : 12/24/2020

Medication Class : Antiviral

Trade Name : Galidesivir

Developer Researcher : BioCryst Pharmaceuticals

Sponsors : NIAID

Trial Phase : Phase 1b

Details : Background: BioCryst is testing whether galidesivir, an antiviral drug with demonstrated broad-spectrum activity in vitro against coronaviruses MERS and SARS, is effective in treating patients with COVID-19. The company is enrolling up to 132 participants in an NIAID-sponsored trial evaluating whether galidesivir is effective in treating yellow fever or COVID-19 (NCT03891420). Outcomes: Results from the first part of the NIAID-sponsored trial announced by BioCryst in a press release indicate that galidesivir was "safe and generally well tolerated" among patients in the trial. However, despite this, the company said they expect NIAID to discontinue pursuing galidesivir's COVID-19 indication in favor of exploring its potential as a treatment for "biodefense threats."

Last Update : 12/4/2020

Medication Class : HIV protease inhibitor

Trade Name : Kaletra (lopinavir-ritonavir)

Developer Researcher : AbbVie

Sponsors : Various

Trial Phase : Phase 2/4

Details : Background: Kaletra is indicated in combination with other antiretrovirals to treat HIV-1 infection in adults and in pediatric patients 14 days and older. Kaletra has been effective against SARS, showing in vitro activity against the disease in a 2004 study. Countries hard hit by COVID-19, such as Italy, have recommended the drug combination as a treatment for the novel coronavirus. Trials: High-profile trials of Kaletra are evaluating the drug alone and in combination with other COVID-19 therapeutic candidates: Tongji Hospital (Recruiting; NCT04255017). A study in South Korea pitting Kaletra against hydroxychloroquine in mild cases of COVID-19 (NCT04307693). Kaletra alone and in combination with interferon-beta are two arms of the WHO SOLIDARITY trial, but have been discontinued due to lack of efficacy. The UK-based RECOVERY trial is also evaluating Kaletra, but has stopped randomization to this treatment arm. Lopinavir and ritonavir are also being evaluated together with abacavir and lamivudine as the drug QuadraMune in a trial sponsored by Therapeutic Solutions International (NCT04421391). Outcomes: Findings are beginning to indicate that Kaletra may not result in clinical improvement from COVID-19. - Evidence for use: A study published in The Lancet found a combination of interferon beta-1b, Kaletra and ribavirin was more effective than treating with Kaletra on its own. - Evidence showing no benefit: A randomized, controlled trial published in the New England Journal of Medicine showed no therapeutic benefit for Kaletra in patients with cases of severe COVID-19. Results from the RECOVERY trial, which were published in The Lancet, researchers found no clinical benefit for hospitalized patients taking Kaletra. In SOLIDARITY, interim results published in the New England Journal of Medicine showed Kaletra and interferon did not reduce mortality, the need for ventilation, or duration of hospital stay. Status: Trial completion dates of the studies based in China and South Korea vary, with the earliest completion dates listed in late April. SOLIDARITY is currently recruiting. RECOVERY has stopped randomizing to its Kaletra arm after finding no clinical benefit for the drug.

Last Update : 10/2/2020

Medication Class : Monoclonal antibody

Trade Name : COVI-GUARD (STI-1499)

Developer Researcher : Sorrento Therapeutics

Sponsors : Sorrento Therapeutics

Trial Phase : Phase 1

Details : Background: Sorrento Therapeutics, Inc. is developing STI-1499, also called COVI-GUARD, a neutralizing antibody that binds to the S1 subunit of the spike protein in SARS-CoV-2. COVI-GUARD is also part of a neutralizing antibody cocktail of three molecules that Sorrento is calling COVI-SHIELD, which is being developed in partnership with Mount Sinai Hospital in New York City. Pre-clinical results from posted to the pre-print server bioRxiv indicate COVI-GUARD protects against SARS-CoV-2 in Syrian golden hamsters. Trial: The company is planning a Phase 1 trial of COVI-GUARD in 32 patients hospitalized with COVID-19 compared with placebo (NCT04454398). Status: On 16 September, Sorrento received approval from the FDA to proceed with the Phase 1 trial for COVI-GUARD. The company said the ultimate goal is to obtain an EUA for COVI-GUARD by the end of the year.

Last Update : 9/25/2020

Medication Class : VIP receptor agonist

Trade Name : PB1046

Developer Researcher : PhaseBio

Sponsors : PhaseBio

Trial Phase : Phase 2

Details : Background: PhaseBio is evaluating their vasoactive intestinal peptide (VIP) receptor agonist PB1046 in hospitalized patients with COVID-19. Results in animal studies demonstrated PB1046 was effective in preventing acute lung injury and stopping inflammatory responses associated with ARDS. A Phase 2 trial of the candidate is underway in up to 210 participants hospitalized with COVID-19 (NCT04433546).

Last Update : 9/18/2020

Medication Class : Small-molecule inhibitor

Trade Name : PF-00835321 (PF-07304814)

Developer Researcher : Pfizer

Sponsors : Pfizer

Trial Phase : Phase 1b

Details : Background: Pfizer is evaluating its phosphate prodrug PF-07304814, which metabolizes to PF-00835321 and has shown antiviral activity in vitro against SARS-CoV-2. The company has started a Phase 1b study of up to 56 participants who will receive the therapeutic or placebo (NCT04535167).

Last Update : 9/11/2020

Medication Class : Monoclonal antibody

Trade Name : Takhzyro (lanadelumab)

Developer Researcher : Takeda (Shire)

Sponsors : Takeda (Shire)

Trial Phase : Phase 1b

Details : Background: Japanese pharmaceutical company Takeda is investigating whether lanadelumab, a monoclonal antibody currently being studied as a treatment for patients with hereditary angioedema, is effective in reducing fluid build-up in the lungs of patients with COVID-19. Lanadelumab blocks the activation of bradykinin, which has been theorized to be responsible for vascular dilation, vascular permeability and hypotension when bradykinin levels increase during COVID-19. Trial: Takeda is conducting a Phase 1 study of up to 24 participants analyzing lanadelumab against standard of care for COVID-19 associated pneumonia (NCT04460105).

Last Update : 9/4/2020

Medication Class : Glucocorticoid

Trade Name : Hydrocortisone

Developer Researcher : Various

Sponsors : Various

Trial Phase : Phase 3

Details : Background: Hydrocortisone is being evaluated in several trials as a treatment to reduce or prevent lung injury and multisystem organ dysfunction associated with COVID-19. Other glucocorticoids such as dexamethasone have been shown to be effective in hospitalized patients who are mechanically ventilated. Trials: In Denmark, hydrocortisone is being evaluated in a Phase 3 trial of up to 1,000 participants with COVID-19 and severe hypoxia (NCT04348305). It also is being studied in France at Tours University Hospital in a subgroup of participants in the Phase 3 CAPE_COD trial evaluating its effect on treating community-acquired pneumonia (NCT02517489). Outcomes: A meta-analysis of studies from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group analyzing the effect of dexamethasone, hydrocortisone, and methylprednisolone on mortality in patients with COVID-19 found systemic corticosteroids were effective in reducing 28-day mortality compared with usual care. Results from CAPE_COD published in JAMA found low-dose hydrocortisone was not effective in reducing mortality or persistent respiratory support compared with placebo, but researchers suggested the study may have been underpowered to detect a significant difference in outcomes. Results from the REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial, also published in JAMA, suggested hydrocortisone may be beneficial for patients with COVID-19, but the trial was stopped early. Status: Treatment guidelines released by NIH on 27 August recommend the use of dexamethasone at a dose of 6 mg per day for hospitalized patients with COVID-19 who meet certain criteria, or the use of prednisone, methylprednisolone, or hydrocortisone when dexamethasone is not available.

Last Update : 8/28/2020

Medication Class : Small-molecule protein inhibitor

Trade Name : BLD-2660

Developer Researcher : Blade Therapeutics

Sponsors : Blade Therapeutics

Trial Phase : Phase 2

Details : Background: BLD-2660, an oral small-molecule inhibitor of calpain, is being investigated as a therapeutic candidate for treating pneumonia associated with COVID-19. Its developer, Blade Therapeutics, is performing a Phase 2 randomized, double-blinded, placebo-controlled trial of BLD-2660 in up to 120 participants hospitalized with COVID-19 (NCT04334460) The company said the candidate is also being tested with concomitant remdesivir, according to a press release.

Last Update : 8/21/2020

Medication Class : Recombinant human plasma

Trade Name : Rhu-pGSN (gelsolin)

Developer Researcher : BioAegis Therapeutics

Sponsors : BioAegis Therapeutics

Trial Phase : Phase 2

Details : Background: BioAegis Therapeutics is assessing whether Rhu-pGSN, their recombinant human plasma product, is effective in treating hospitalized patients with COVID-19 who have developed pneumonia. Rhu-pGSN has shown in pre-clinical testing to regulate inflammation and has the potential to suppress cytokine release syndrome associated with COVID-19. Trial: The company has been approved by The Spanish Agency for Medicines and Health Products (AEMPS) to test whether Rhu-pGSN performs better than placebo in a randomized, blinded, placebo controlled trial (NCT04358406).

Last Update : 7/30/2020

Medication Class : PIKfyve inhibitor

Trade Name : LAM-002A (apilimod dimesylate)

Developer Researcher : AI Therapeutics, Inc.

Sponsors : AI Therapeutics, Inc.,Yale University

Trial Phase : Phase 2

Details : Background: AI Therapeutics and the Yale Center for Clinical Investigation are examining the efficacy of LAM-002A, a PIKfyve kinase inhibitor, in newly diagnosed patients with COVID-19. Preliminary research has shown LAM-002A combats SARS-CoV-2, especially in lung cells. Study Design: A phase 2 randomized, double-blind, placebo-controlled trial of about 142 participants who will receive LAM-002A 125mg in five 25-mg capsules twice per day for 10 days, or microcrystalline cellulose as a placebo (NCT04446377).

Last Update : 7/30/2020

Medication Class : RIPK1 inhibitor

Trade Name : DNL758 (SAR443122)

Developer Researcher : Sanofi,Denali Therapeutics

Sponsors : Sanofi

Trial Phase : Phase 1b

Details : Background: Biopharmaceutical company Denali Therapeutics and Sanofi are partnering to test DNL758, a peripherally-restricted small molecule inhibitor of RIPK1, in a Phase 1b study of patients hospitalized with severe COVID-19. DNL758 is thought to reduce excessive inflammation associated with severe cases of COVID-19, according to a company press release. Study Design: A Phase 1b, randomized, double-blinded, placebo-controlled trial of 67 participants hospitalized with severe COVID-19 (NCT04469621).

Last Update : 7/2/2020

Medication Class : Autologous adipose-derived stem cells

Trade Name : AdMSCs

Developer Researcher : Celltex Therapeutics

Sponsors : Celltex Therapeutics

Trial Phase : Phase 2

Details : Background: Previous research has shown ACE2- mesenchymal stem cells were safe and effective in treating pneumonia associated with COVID-19. Trial: A Phase 2, multicenter, double-blinded study of 200 healthy participants where 100 participants who have already banked their AdMSCs with Celltex will receive three infusions of cells to test whether they have a prophylactic effect against COVID-19 (NCT04428801). Regulatory Actions: FDA has approved an IND to evaluate AdMSCs in a Phase 2 study.

Last Update : 6/25/2020

Medication Class : Mitogen-activated protein kinase (MAPK) inhibitor

Trade Name : Losmapimod

Developer Researcher : Fulcrum Therapeutics

Sponsors : Fulcrum Therapeutics

Trial Phase : Phase 3

Details : Background: Losmapimod is a p38α/β MAPK inhibitor thought to reduce the inflammatory response associated with disease progression in COVID-19 by reducing inflammatory biomarkers such as C-reactive protein and IL-6. Trials: Fulcrum is launching the Phase 3 LOSVID study, which will evaluate around 400 patients with COVID-19 who will receive a dose of the drug or placebo (NCT04511819). Regulatory Actions: FDA has approved an IND to test losmapimod in the Phase 3 study.

Last Update : 5/14/2020

Medication Class : Monoclonal antibody

Trade Name : Gimsilumab

Developer Researcher : Roivant Sciences

Sponsors : Roivant Sciences

Trial Phase : Phase 2

Details : Background: Gimsilumab targets the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), which researchers have seen elevated in the blood of patients with COVID-19 and may be associated with acute respiratory distress syndrome in these patients. Trials: Roivant has announced their randomized, double-blinded, placebo-controlled BREATHE trial will evaluate the efficacy of intravenous gimsilumab in 270 patients with COVID-19 with ARDS or lung injury (NCT04351243) . Status: On 15 April, Roivant announced the first patient in the trial had been treated. On 13 May, Roivant said they would allow participants in the BREATHE trial to use convalescent plasma or antiviral agents like remdesivir in addition to receiving gimsilumab or placebo.


Data Source

Live Data Source: Worldometers
Data by date John Hopkins University & Pomber from github: John Hopkins - Pomber
Bangladesh District Wise Data source: dghs.gov.bd
Vaccine Tracker Data Source: The New Work Times
Get vaccine trial data from RAPS (Regulatory Affairs Professional Society). Specifically published by Jeff Craven: RAPS
Get therapeutics trial data from RAPS (Regulatory Affairs Professional Society). Specifically published by Jeff Craven: RAPS
USA Data Source: Worldometer
India Data Source: Get COVID-19 government reported data for a specific country
API for covid19: Corona Ninja