COVID-19 Drug Research Roundup

COVID-19 Therapies:

Researchers from the U.S. and Brazil have examined proxalutamide, a novel second-generation androgen receptor antagonist, as a treatment for patients with mild-to-moderate COVID-19 in a double-blind, placebo-controlled phase 2 trial. By day seven, SARS-CoV-2 became undetected in approximately 82 percent of patients who were randomly assigned to proxalutamide vs. 31 percent of patients in the placebo arm. In the 236-person study, sponsored by Applied Biology, the mean clinical remission time was also significantly shorter with proxalutamide (4.2 days) vs. placebo (21.8 days). The researchers of this study plan to confirm their findings in a currently recruiting trial of 600 patients in Brazil.

A phase 1 trial sponsored by the National Institutes of Health has found that Regeneron’s two monoclonal antibodies, REGN3048 and REGN3051, were generally safe and well-tolerated when given to 36 healthy adults. The monoclonal antibodies were developed by Regeneron to target the coronavirus spike protein involved in Middle East Respiratory Syndrome (MERS). The investigators observed no serious adverse events associated with the antibodies in these participants. Researchers from Regeneron and the University of Maryland, College Park, also gave REGN3048 and REGN3051 to genetically modified mice prior to coronavirus exposure and found that the antibodies reduced the levels of MERS coronavirus in the lungs. The animal model showed that the antibodies were more effective when administered at the same time.

Revive Therapeutics says it plans to expand its phase 3 COVID-19 clinical trial of bucillamine to include up to 50 clinical sites vs. the 14 clinical sites included in the original trial design. The randomized, placebo-controlled trial is evaluating the efficacy and safety of bucillamine in patients with mild-to-moderate COVID-19. Revive plans to enroll up to 1,000 patients, all of whom will be randomized to receive either bucillamine or placebo for 14 days. The primary efficacy endpoint of the study is the percentage of patients who meet a composite endpoint of hospitalization or death through day 28. Efficacy and safety data are being examined at each interim analysis of 210, 400, 600 and 800 completed patients. So far, the analyzed data from the 210 participants at the interim time point has found no serious safety concerns associated with the studied treatment.

Sponsors of the global, adaptive clinical trial known as REMAP-CAP are now including Merck’s ivermectin in the study to see if it offers any real-world benefit for COVID-19. Some doctors in hospitals across the UK have reportedly been using ivermectin off-label for the treatment of COVID-19, despite the fact that the drug hasn’t been authorized for this indication. The REMAP-CAP trial has incorporated ivermectin even while the therapy faces conflicting views regarding its efficacy for COVID-19. More than 40 trials that have studied ivermectin at safe dosages suggest the drug may hold utility as a potential COVID-19 treatment, but evidence generated from the REMAP-CAP trial should help inform whether the findings from these smaller trials hold weight in a larger population.

Vir Biotechnology and GlaxoSmithKline will no longer administer their experimental COVID-19 antibody treatment VIR-7831 to new patients in a U.S. arm of a phase 3 study examining potential COVID-19 treatments. The decision was made after the trial’s independent safety and monitoring board suggested that current data do not show whether VIR-7831 can provide a clear, meaningful benefit for treating the novel coronavirus. The drugmakers say the safety data are promising, however, and they are waiting for further efficacy data to mature before they make a final decision on whether to reopen the VIR-7831 trial arm. Currently, VIR-7831 is also undergoing evaluation in an ongoing phase 2 study, which combines the antibody with Eli Lilly’s bamlanivimab as an approach to mild-to-moderate COVID-19.

The FDA has approved Sorrento Therapeutics’ investigational new drug application for a phase 1 study of an antibody nose drop formulation dubbed STI-2099 (COVIDROPS). The study will examine the safety and pharmacokinetics of STI-2099 in healthy volunteers as well as in patients with mild COVID-19. The therapy is being assessed against the most dominant wild type strain of the virus found in the U.S. and an emerging strain from the UK. In addition, Sorrento says it plans to test the intranasal version of the therapy alone or combined with an intravenous version in patients with newly diagnosed COVID-19.

Global virtual research organization ObvioHealth has launched a phase 2/3 hybrid COVID-19 trial in the U.S. that will examine the safety and efficacy of RedHill Biopharma’s RHB-107 (upamostat) for symptomatic COVID-19. The two-part, double-blind trial is enrolling more than 300 patients with COVID-19 who do not need hospital care. Vitals collected via a digital data capture during the trial will include body temperature, blood pressure, respiratory and pulse rates, electrocardiogram, pulse oximetry and weight. While some data will be captured by the patients using digital devices and a smartphone app, home healthcare nurses will also make in-home visits to collect blood samples and perform virus swabs. The researchers hope that this combined data-capturing approach could allow them to act quickly if a patient experiences an adverse event while on treatment.

Following positive findings from a 40-person phase 2 clinical trial, Veru says it plans to advance its oral COVID-19 drug candidate VERU-111 into a phase 3 registration trial. The study will examine the efficacy and safety of the oral, novel chemical entity in hospitalized patients with high-risk disease. The 400 hospitalized patients with COVID-19 enrolled in this trial will be randomized to either receive VERU-111 (267 patients) or placebo (133 patients). The researchers will compare the two groups in terms of the proportion of patients who are still alive at day 29.

Merck plans to launch a new phase 3 trial of an investigational COVID-19 treatment it gained from a $425 million acquisition of OncoImmune. While a previous trial had already tested the efficacy of the candidate, called MK-7110 (CD24Fc), the FDA says too few participants were enrolled to support regulatory authorization. The previous 243-participant trial showed that the anti-inflammatory drug offered a greater than 50 percent reduction in the risk of mortality or respiratory failure in hospitalized patients with moderate-to-severe COVID-19. Under a $356 million supply agreement with the government, Merck previously said it would supply up to 100,000 MK-7110 doses by June. Merck is also evaluating another antiviral COVID-19 candidate called MK-4482. The therapy was evaluated in a small phase 2a study and is currently undergoing investigation in another phase 2a study and two larger phase 2/3 trials.

The National Institutes of Health has stopped a clinical trial that was evaluating convalescent plasma as a potential treatment option for COVID-19. The trial was halted based on recommendations from an independent review committee, which found in a second planned interim analysis that the therapy, obtained from patients who recovered from COVID-19, was unlikely to offer a meaningful benefit to patients with mild-to-moderate COVID-19 in the emergency room. Despite an apparent lack of benefit, convalescent plasma did not increase the risk of harm for patients.

COVID-19 Vaccines:

A phase 2a/b trial from South Africa shows Novavax’s COVID-19 vaccine candidate was 51 percent effective against the B.1.351 SARS-CoV-2 variant in HIV-negative patients. The study enrolled 4,387 volunteers with COVID-19, including patients who were HIV-positive. A total of 2,199 participants in the vaccine group received two doses of the Novavax vaccine 21 days apart. Up to 93 percent of COVID-19 cases in this study were caused by the South African variant. The efficacy rates of the vaccine were 60.1 percent in HIV-negative patients and 49.4 percent in HIV-positive patients. The study findings follow results from a phase 3 study in the UK, which showed the same vaccine was 89.3 percent effective for preventing symptomatic COVID-19.

An interim analysis of a late-stage trial shows Bharat Biotech’s COVID-19 vaccine candidate Covaxin (BBV152) was effective at preventing COVID-19 in 80.6 percent of trial participants who received two doses at two weeks apart. The study has enrolled 25,800 participants in the trial to date. In the first interim analysis, a total of 43 cases of COVID-19 were observed, with 36 of these infections seen in the placebo arm. Researchers said the vaccine also featured activity against variants of the novel coronavirus. The second interim analysis of the trial will be conducted once the study records 87 confirmed COVID-19 cases, and the final analysis will be performed at 130 cases. While Bharat’s vaccine has not yet been approved in the U.S., the vaccine was authorized for emergency use in India before the phase 3 interim analysis was conducted.

China’s National Medical Products Administration has granted conditional approval for two COVID-19 vaccines made by CanSino Biologics and a unit of Sinopharm. The approvals were made after clinical trials found both vaccines were effective for protecting against COVID-19. The Wuhan Institute of Biological Products recently said that Sinopharm’s vaccine had an efficacy rate of 72.5 percent in clinical trials. In total, China has approved four domestic COVID-19 vaccines. China has yet to authorize COVID-19 vaccines developed by Western drugmakers.

Inovio Pharmaceuticals recently completed enrollment of 400 participants in its phase 2 segment of the phase 1/2 INNOVATE trial, which is studying the efficacy of Inovio’s COVID-19 DNA vaccine INO-4800. The trial, funded by the Department of Defense, is expected to conclude in the second quarter of this year. Inovio said in a recent announcement that it is also investigating its COVID-19 vaccine against new and emerging viral variants. Also, the company said it is testing whether INO-4800 could be used as an effective seasonal booster shot in a phase 1 vaccine trial of 120 patients. Immunogenicity data from this small trial are expected by the second quarter of this year.

A study sponsored by the National Institute of Allergy and Infectious Diseases and in collaboration with the Immune Tolerance Network and contract research organization Rho Federal Systems Division is launching a major clinical trial to investigate severe allergic reactions in patients who receive the Moderna or Pfizer/BioNTech COVID-19 vaccines. The multicenter, randomized phase 3 trial will include up to 3,400 participants who will be divided into two populations, including 2,040 people with a history of allergic reactions or mast-cell disorder and 1,360 people without a history of allergy. Participants will receive placebo for the first dose, followed by two doses of an assigned active COVID-19 vaccine.

The UK-based OCTAVE trial, funded by the Medical Research Council (MRC), has launched a trial to study the effectiveness of COVID-19 vaccines in up to 5,000 patients with cancer, inflammatory arthritis and kidney or liver diseases requiring stem-cell transplant. These three populations typically have impaired immune systems, placing them at a higher risk of more severe COVID-19-related complications compared with the general public. Researchers will examine immune responses in these patients by evaluating blood samples obtained before and/or after vaccination. Immune responses from the patients with the three diseases will be compared with responses from a healthy control group without underlying conditions.