COVID-19 Disease Treatments
On August 23, 2020, COVID-19 Convalescent Plasma was issued a EUA by the FDA. On February 4, 2021, the FDA revised the Letter of Authorization for COVID-19 convalescent plasma to limit the authorization to the use of high titer COVID-19 convalescent plasma only for the treatment of hospitalized patients with COVID-19 early in the disease course and to those hospitalized patients who have impaired humoral immunity and cannot produce an adequate antibody response. Plasma with low levels of antibodies is not helpful in COVID-19, wrote RADM Denise M. Hinton, Chief Scientist, FDA.
On October 22, 2020, the FDA approved the antiviral drug Veklury (remdesivir) to treat patients with COVID-19 requiring hospitalization.
On November 9, 2020, the FDA issued emergency authorization for Eli Lilly's investigational monoclonal antibody therapy Bamlanivimab to treat mild-to-moderate COVID-19 in adult and pediatric patients. This EUA has been modified by the U.S. FDA, issuing an additional EUA on February 9, 2021, for bamlanivimab and etesevimab administered together to treat mild to moderate COVID-19 in certain patients. On April 16, 2021, Lilly requested the withdraw of the single-use EUA.
Additionally, on November 21, 2020, the FDA authorized REGEN-COV (casirivimab and imdevimab) to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients 12 years of age or older weighing at least 88 pounds) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19. This emergency authorization includes 65 years of age or older or certain chronic medical conditions.
On December 23, 2020, Merck announced it has entered into an agreement with the U.S. Government to support the development, manufacture, and initial distribution of an investigational biological therapeutic (CD24Fc, to be named MK-7110) upon approval or Emergency Use Authorization from the U.S. FDA. Merck acquired MK-7110 through the acquisition of New Jersey-based OncoImmune.
Actemra (Tocilizumab), an anti-inflammatory drug used to treat rheumatoid arthritis, has been reported to improve severely ill COVID-19 patients' outcomes. On March 5, 2021, based on the REMAP-CAP and RECOVERY trials' collective evidence, the COVID-19 Treatment Guidelines Panel published updated Recommendations.
Late-Stage Experimental COVID-19 Disease Therapies
Olumiant (baricitinib), an oral JAK1/JAK2 inhibitor, is evaluated in a phase 3 study in hospitalized adults with COVID-19 disease. Study investigators noted an approximately one-day reduction in median recovery time for the overall patient population treated with baricitinib combined with remdesivir versus those treated with remdesivir.
According to the RECOVERY trial, dexamethasone (glucocorticoid) reduced deaths in hospitalized patients with severe COVID-19 disease by one-third compared to those receiving usual care.
Aviptadil (RLF-100) is a formulation of synthetic human Vasoactive Intestinal Peptide, which targets the VPAC1 receptor of the ATII cell and protects that cell against all manner of injuries, including smoke inhalation, exposure to stomach acid, and exposure to infectious agents. The U.S. FDA granted Expanded Access Protocol to RLF-100 (Aviptadil) for Respiratory Failure in COVID-19.
Tradipitant may accelerate clinical improvement in hospitalized COVID-19 pneumonia patients reported a phase 3 study. Tradipitant is an experimental drug that is a neurokinin 1 antagonist. It works by blocking substance P, a small signaling molecule.
Early-Stage Experimental COVID-19 Therapies
Molnupiravir (MK-4482/EIDD-2801) is an oral antiviral medication originally developed to treat influenza. MK-4482/EIDD-2801 consists of the nucleoside analog N4-hydroxycytidine. Molnupiravir has been evaluated against coronaviruses, suppressing virus transmission within 24-hours.
CytoDyn's Leronlimab is in early clinical trials to treat COVID-19 disease. Leronlimab is intended to serve as a therapy for patients who experience respiratory illness due to contracting the Coronavirus Disease 2019 (COVID-19). CytoDyn has met its 75-patient enrollment target in its Phase 2 clinical trial for COVID-19, a randomized clinical trial for mild-to-moderate COVID-19 population in the U.S., and enrollment continues in its Phase 2b/3 randomized clinical trial for severe and critically ill COVID-19 population in several hospitals throughout the country.
Vir and GSK's VIR-7831 (GSK4182136) is a single-dose monoclonal antibody that can prevent hospitalization due to COVID-19 disease. Bamlanivimab and etesemivab have been designed to attach to the spike protein of SARS-CoV-2 at two different sites. When they attach to the spike protein, the virus cannot enter the body’s cells. Because the antibodies attach to different parts of the protein, using them in combination may have a greater effect than either alone.
AstraZeneca's AZD7442 long-acting antibody combination (LAAB) is launching late-stage clinical studies in various countries. Combining two LAABs is also designed to reduce the risk of resistance developed by the SARS-CoV-2 virus.
Roche and Atea's AT-527 has demonstrated clinical safety/tolerability and potent antiviral efficacy in patients with HCV infection, as well as a favorable human pharmacokinetic profile, with potent in vitro activity against human coronaviruses.
Pfizer Inc. is evaluating an investigational, novel oral antiviral clinical candidate PF-07321332, a SARS-CoV2-3CL protease inhibitor, which has demonstrated potent in vitro anti-viral activity against SARS-CoV-2, as well as activity against other coronaviruses, suggesting potential for use in the treatment of COVID-19 as well as potential use to address future coronavirus threats.
April 2021 COVID-19 Treatment News
April 21, 2021 - South Dakota-based SAB Biotherapeutics announced that the first patient has been dosed in its Phase 2/3 study evaluating the safety and efficacy of SAB-185, a polyclonal antibody therapeutic candidate in non-hospitalized adults with mild to moderate COVID-19 as part of the NIH’s ACTIV-2 master protocol. SAB-185 is currently being evaluated in Phase 1 and Phase 1b studies for the treatment of COVID-19, both of which have completed enrollment.
April 20, 2021 - California-based Sorrento Therapeutics, Inc. (Nasdaq: SRNE) announced the completion of enrollment in its Phase 1b study of human allogeneic adipose-derived mesenchymal stem cells (COVI-MSC™) infusions to treat COVID-19 induced acute respiratory failure (ARD) or acute respiratory distress syndrome (ARDS). The study met its primary objective: to demonstrate the safety of intravenous infusion of allogeneic adipose MSC cells in ten patients with COVID-19-induced ARD or ARDS. Sorrento will be working with the FDA shortly once the full dataset is available to plan a placebo-controlled pivotal study to support an emergency use authorization submission.
April 19, 2021 - Israel-based Todos Medical, Ltd. (OTCQB: TOMDF) announced the initiation of a randomized, double-blind, placebo-controlled Phase 2 clinical trial of its antiviral NLC-V-01, a potent 3CL protease inhibitor, for the treatment of hospitalized COVID-19 patients. The trial, being conducted at Shaare Zedek Medical Center in Jerusalem, Israel, will evaluate the safety and efficacy of Tollovir for the treatment of COVID-19 in hospitalized patients.
April 19, 2021 - New Jersey-based Tonix Pharmaceuticals Holding Corp. and OyaGen, Inc. announced an exclusive worldwide licensing agreement for an antiviral inhibitor of SARS-CoV-2, TNX-3500 (sangivamycin, formerly OYA1), for the treatment of COVID-19 and potentially other viral disorders. The active ingredient of TNX-3500 has been studied for safety in humans in prior studies on cancer patients at the U.S. National Cancer Institute. Still, it has not been approved for marketing in any jurisdiction.
April 19, 2021 - Norway-based BerGenBio ASA (OSE: BGBIO) announced an update from the Phase II clinical study evaluating the efficacy and safety of bemcentinib in hospitalized COVID-19 patients (BGBC020). Throughout both studies, bemcentinib was well tolerated by patients, and no safety signals of concern were reported. On day 29, a numerically lower number of deaths were reported in the bemcentinib arm of both studies: In ACCORD2, 1 death in 28 patients treated with bemcentinib and SoC versus 5 in 32 patients treated with SoC alone, and 2 vs. 3 in BGBC020.
April 16, 2021 - Eli Lilly and Company requested the U.S. Food and Drug Administration revoke the Emergency Use Authorization for bamlanivimab (LY-CoV555) 700 mg alone. Lilly made this request due to the evolving variant landscape in the U.S. and the full availability of bamlanivimab and etesevimab together. This request is not due to any new safety concerns.
April 15, 2021 - The National Institute of Allergy and Infectious Diseases announced that the fourth iteration of the Adaptive COVID-19 Treatment Trial has closed to enrollment because the study met pre-defined futility criteria indicating that neither treatment regimen studied is likely significantly better than the other. The trial aimed to determine which two-drug combination, baricitinib plus remdesivir or dexamethasone plus remdesivir, was more effective at preventing adults hospitalized with COVID-19 on supplemental oxygen from progressing to requiring mechanical ventilation or death, among other outcomes.
April 12, 2021 - Kiniksa Pharmaceuticals, Ltd. announced the Phase 2 portion of the Phase 2/3 trial of mavrilimumab in non-mechanically-ventilated patients (Cohort 1) with severe COVID-19 pneumonia and hyper inflammation achieved its primary efficacy endpoint of the proportion of patients alive and free of mechanical ventilation at Day 29. Mavrilimumab is an investigational fully-human monoclonal antibody that targets granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFRα).
April 12, 2021 - Eli Lilly and Company announced the company and the U.S. government agreed to modify the existing purchase agreement of bamlanivimab alone and focus on future supplies of bamlanivimab and etesevimab together. This action terminates the purchase agreement for bamlanivimab alone and cancels the remaining 350,856 doses scheduled to be delivered to the US government by the end of March 2021. Additionally, the bamlanivimab and etesevimab agreement has been modified to enable the supply of etesevimab to complement doses of bamlanivimab the U.S. government already purchased.
April 8, 2021 - Eli Lilly and Incyte announced results of COV-BARRIER, a Phase 3 study evaluating baricitinib 4 mg once daily plus standard of care (SoC) versus placebo plus SoC. The trial did not meet statistical significance on the primary endpoint, which was defined as a difference in the proportion of participants progressing to the first occurrence of non-invasive ventilation including high flow oxygen or invasive mechanical ventilation including extracorporeal membrane oxygenation (ECMO) or death by Day 28. Baricitinib-treated patients were 2.7 percent less likely than those receiving standard of care to progress to ventilation (non-invasive or mechanical) or death, a difference that was not statistically significant (odds ratio [OR]: 0.85; 95% CI 0.67, 1.08; p=0.1800).
April 7, 2021 - The Lancet published: SARS-CoV-2 spike E484K mutation reduces antibody neutralization.
April 5, 2021 - Vir Biotechnology, Inc. today announced new preclinical research demonstrating the ability of VIR-7831, the company’s investigational SARS-CoV-2 monoclonal antibody (mAb), to maintain its neutralizing activity against a mutation in the receptor-binding domain (RBD) of SARS-CoV-2, called L452R, which is found in the California variant (B.1.427/B.1.429). Study results also demonstrate that the L452R mutation reduced both the neutralization potency of plasma from vaccinated and convalescent donors and the neutralization activity of 14 RBD-specific and 10 N-terminal domain-specific monoclonal antibodies, including three clinical-stage mAbs.
April 5, 2021 - Massachusetts-based Innovation Pharmaceuticals announced an independent Data Monitoring Committee (DMC) completed its scheduled review of interim safety data in the Company’s randomized, double-blind, placebo-controlled Phase 2 clinical trial of Brilacidin for treatment of moderate-to-severe COVID-19 in hospitalized patients. Upon reaching 25 percent enrollment (30 subjects), recruitment was paused, and the DMC conducted a pre-specified unblinded safety data review and evaluation. Following their review, the DMC recommended increasing the dosing regimen of Brilacidin from 3 days to 5 days of treatment, as intended per the protocol, which the Company has since implemented. Recruitment for the 5-day treatment regimen has begun. Efficacy data was not reviewed by the DMC and remained blinded.
March 2021 COVID-19 Treatment News
March 31, 2021 - The current evidence on using ivermectin to treat COVID-19 patients is inconclusive. Until more data is available, the WHO recommends that the drug only be used within clinical trials. This recommendation, which applies to patients with COVID-19 of any disease severity, is now part of the WHO’s guidelines on COVID-19 treatments.
March 26, 2021 - GlaxoSmithKline plc and Vir Biotechnology, Inc. announced submitting an application to the U.S. Food and Drug Administration requesting Emergency Use Authorization for VIR-7831 (GSK4182136).
March 24, 2021 - A new systematic review and network meta-analysis of randomized controlled trials to provide updated information regarding the clinical efficacy of remdesivir in treating COVID-19. These researchers concluded, 'Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19, and a 5-day regimen, instead of a 10-day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.'
March 24, 2021 - The Russian Direct Investment Fund and the ChemRar Group announce the Favipiravir-based drug Avifavir has been registered by the National Agency of Drug and Food Control of Indonesia. Pratapa Nirmala-Fahrenheit is the partner for the registration and sales of Avifavir in Indonesia.
March 23, 2021 - Pfizer Inc. announced it is progressing to multiple ascending doses after completing the dosing of single ascending doses in a Phase 1 study in healthy adults to evaluate the safety and tolerability of a novel oral antiviral therapy for SARS-CoV-2, the coronavirus that causes COVID-19. The oral antiviral clinical candidate PF-07321332, a SARS-CoV2-3CL protease inhibitor, has demonstrated potent in vitro anti-viral activity against SARS-CoV-2 as activity against other coronaviruses, suggesting potential for use in the treatment of COVID-19 as well as potential use to address future coronavirus threats.
March 23, 2021 - The REGEN-COV phase 3 clinical trial outcomes of the Casirivimab with Imdevimab antibody cocktail in high-risk non-hospitalized COVID-19 patients reduced the risk of hospitalization or death by 70% compared to placebo. Additionally, dose-ranging in phase 2 clinical trial of the cocktail showed significant and comparable viral reductions for all REGEN-COV doses tested, including as low as 300 mg.
March 15, 2021 - Switzerland-based Molecular Partners AG and its collaborator Novartis announced that ensovibep (formerly MP0420) is expected to be included in a global phase 3 randomized, controlled clinical trial as part of the US National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program. Ensovibep is a DARPin® therapeutic candidate designed to bind to the receptor-binding domain of the SARS-CoV-2 spike protein at three distinct locations to prevent viral entry into cells and provide added protection against variant strains.
March 11, 2021 - The EMA’s human medicines committee has started a ‘rolling review’ of data on the antibodies bamlanivimab and etesemivab, which are being developed by Indiana-based Eli Lilly and Company to be used in combination for the treatment of COVID-19. The review will also look at bamlanivimab used alone.
March 10, 2021 - North Carolina-based EmitBio Inc. announced new evidence demonstrating its proprietary light technology could inactivate variants of the coronavirus that causes COVID-19, including the highly infectious United Kingdom and South Africa variants. These findings indicate important effectiveness against potentially more transmissible mutations of COVID-19. EmitBio™ has developed a novel, hand-held treatment device* that directs energy into the upper respiratory tract with 100% of the dose available in the area of need, thereby avoiding the possible side effects of systemic treatments. This device has been designed as an at-home treatment for mild-tomoderate COVID-19 in adults testing positive for SARS-CoV-2.
March 8, 2021 - Researchers from the University of Bristol and Medanta Institute of Education and Research in India announced a study in The Lancet Respiratory Medicine. They concluded routine use of tocilizumab in patients admitted to the hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests that tocilizumab might still be effective in patients with severe COVID-19 and should be investigated further in future studies. Analysis of the data revealed a subset of patients with severe disease in whom tocilizumab might have a reduced risk for progression to death if treated with tocilizumab in addition to normal care.
March 5, 2021 - Eli Lilly and Company announced that the European Medicines Agency's Committee for Medicinal Products for Human Use had issued a positive scientific opinion for bamlanivimab alone bamlanivimab administered together with etesevimab. The Agency concluded that bamlanivimab and etesevimab could be used together to treat confirmed COVID-19 in patients who do not require supplemental oxygen and are at high risk of their COVID-19 disease severe. The Agency also looked at the use of bamlanivimab alone and concluded that it could be considered a treatment option despite uncertainties around monotherapy benefits.
March 4, 2021 - JAMA published Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19. Conclusion and Relevance Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolve symptoms. The findings do not support the use of ivermectin for the treatment of mild COVID-19. However, larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.
March 3, 2021 - San Francisco-based Vir Biotechnology, Inc. and GlaxoSmithKline plc provided an update on the VIR-7831 (GSK4182136) arm of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines Program Phase 3 clinical trial. The companies were informed that while VIR-7831 met initial pre-specified criteria to continue to the next phase of the ACTIV-3 trial and there were no reported safety signals, sensitivity analyses of the available data raised concerns about the magnitude of potential benefit.
March 3, 2021 - Massachusetts-based eXIthera Pharmaceuticals announced the U.S. Food and Drug Administration had accepted its Investigational New Drug (IND) application to initiate a Phase 2 clinical trial for EP-7041, a parenteral, potent, and selective small-molecule inhibitor of coagulation Factor XIa. The IND application indicates EP-7041 is an investigational treatment for COVID-19, addressing the increased morbidity and mortality risk due to blood clot formation in critically ill patients with COVID-19.
March 3, 2021 - Quebec-based Altasciences is pleased to support ReAlta Life Sciences by conducting a Phase I trial to evaluate RLS-0071 to treat Acute Lung Injury (ALI) from viral infections such as SARS-CoV-2, respiratory syncytial virus, and influenza. As part of the ReAlta ALI program underway, the Phase I trial is a single-ascending dose, randomized, double-blind, placebo-controlled, adaptive-design study to evaluate the safety, tolerability, PK, and PD of RLS-0071 in healthy subjects, performed at the Altasciences clinical pharmacology unit in Montreal, Canada.
March 2, 2021 - California-based Sorrento Therapeutics, Inc. announced that it had received clearance from the FDA for its Investigational New Drug application for its Phase 1 study of safety pharmacokinetics of intranasal STI-2099 (COVIDROPS) in both healthy volunteers and patients with mild COVID-19.
Previous COVID-19 and SARS-CoV-2 Treatment News are found on this CoronavirusToday webpage.
Note: This content was last reviewed by health care professionals, such as Dr. Robert Carlson.