COVID-19 Drug Research Roundup

COVID-19 Therapies:

Merck’s ivermectin product Stromectol did not improve the rate of recovery better than placebo in patients with mild COVID-19, according to findings from a randomized clinical trial. The study included 476 patients who were enrolled at a single site in Columbia. Treatment with ivermectin in this trial led to symptom resolution after a median of 10 days vs. 12 days in the placebo group. Approximately 82 percent of patients in the ivermectin arm and 79 percent of participants in the placebo group experienced symptom resolution by day 21. Multiorgan failure was the most common serious adverse event, which occurred in two patients in each arm.

Ridgeback Biotherapeutics’ and Merck’s co-developed experimental antiviral candidate MK-4482 (molnupiravir) significantly reduced COVID-19 infection after five days in a multicenter, phase 2a trial. The trial included 202 nonhospitalized patients with SARS-CoV-2 infection. None of the patients who received molnupiravir had a positive COVID-19 test result after five days, while 24 percent of patients in the placebo group still had a positive test result for the novel coronavirus. Patients treated early in the course of their disease also experienced a faster reduction in infectious virus if they were treated with molnupiravir. Merck says it is currently planning to launch a phase 3 study to evaluate MK-7110 (CD24Fc), a Merck-acquired investigational COVID-19 agent, to support data from another study that didn’t have enough participants to support an Emergency Use Authorization or approval.

The ongoing UK-based RECOVERY trial has halted enrollment of patients in a treatment arm evaluating the anti-inflammatory gout drug colchicine. Researchers added the colchicine arm to the trial last year after it showed potential in previous research for the management of severely ill hospitalized patients with COVID-19 who required mechanical ventilation. Enrollment was halted after an independent data monitoring committee found the drug provided no clinical benefit in a review of efficacy data that involved 11,162 patients. Colchicine ultimately had no significant benefit on 28-day mortality compared with standard of care in this patient population. The RECOVERY trial will continue to enroll for other trial arms, including those evaluating Roche’s arthritis agent Actemra (tocilizumab), Regeneron’s antibody cocktail comprising casirivimab and imdevimab, as well as dimethyl fumarate and aspirin.

Phase 2 and 3 trials show Eli Lilly’s monoclonal antibody bamlanivimab reduces viral load and symptoms of COVID-19 and also reduces COVID-19-related hospitalizations by up to 70 percent. A combination regimen consisting of bamlanivimab and Lilly’s etesevimab also reduced COVID-19-related hospitalizations and death by 70 percent in high-risk patients and those with mild-to-moderate COVID-19. Based on these data, the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended Lilly’s monoclonal antibodies as potential COVID-19 treatments. This positive recommendation will likely influence the European Commission to authorize the use of the antibodies for COVID-19.

The late stage of the National Institutes of Health’s (NIH) ACTIV-3 trial will not evaluate Brii Biosciences’ investigational monoclonal antibodies BRII-196 and BRII-198 after a trial found the two agents did not reach the minimum required efficacy rate for hospitalized COVID-19 patients. The decision was made to not move forward with BRII-196 and BRII-198 based on an evaluation of safety and efficacy for the combined antibodies in 150 hospitalized patients with COVID-19. Brii’s BRII-196 and BRII-198 are both derived from the plasma of patients who have recovered from COVID-19. While NIH will not move forward with evaluating these agents, Brii says it will continue to evaluate the antibody combination in ambulatory patients with COVID-19.

The NIH has launched another ACTIV-4 phase 3 trial that is focusing on the use of blood thinners to prevent life-threatening blood clots in discharged patients with moderate-to-severe COVID-19. The first patient was enrolled in the trial on Feb. 15. The trial will first focus on the use of Bristol Myers Squibb/Pfizer’s blood thinner Eliquis® (apixaban) in discharged patients with a diagnosis of moderate-to-severe COVID-19. Researchers of the trial will evaluate whether patients randomized to apixaban experience a lower rate of any thrombotic complication within 45 days compared with patients randomized to placebo. To date, the ACTIV-4 adaptive clinical trials are being conducted at more than 100 sites across the globe.

A phase 3 trial has found that CytoDyn’s CCR5 antagonist candidate Vyrologix (leronlimab) improved survival and reduced hospital stay in critically ill hospitalized patients with COVID-19. Treatment with leronlimab in this trial led to a 24 percent reduction in all-cause mortality compared with placebo. Additionally, patients treated with leronlimab had a six-day shorter hospital stay compared with those who received placebo. Overall, patients who received leronlimab had a 166 percent better improvement in their probability of being alive at discharge by day 28. CytoDyn says it has reported the trial data to the FDA and the UK’s Medicines and Healthcare product Regulatory Agency as well as Health Canada to see what next steps are necessary to ensure ultimate approval for the therapy in COVID-19. The company has also filed an additional protocol with the FDA to include more patients with severe COVID-19 at existing study sites.

A newly launched pilot study is testing the safety of a combination of 13 traditional Chinese medicinal compounds in patients with COVID-19. These compounds were used early during the COVID-19 pandemic, but large-scale research has yet to confirm their safety or efficacy for fighting the novel coronavirus. Researchers from the University of Southern California are spearheading the pilot study, which will examine the use of Xuanfei Baidu granules in mild-to-moderate COVID-19. The 12-week, placebo-controlled study is fully remote. Investigators will remotely obtain informed consent and monitor patient performance. Data generated from this study should inform the design of larger phase 2 studies evaluating the traditional Chinese medicinal compounds.

A multicenter, open-label clinical trial has shown that treatment with Viriom’s and Chromis’ Avifavir (favipiravir) was associated with a significantly shorter time to elimination of the COVID-19 virus compared with standard of care in hospitalized patients with medium-severe-to-severe COVID-19. In the trial, a total of 470 patients were randomized to receive either favipiravir or standard of care. Researchers found that the median time to clinical improvement was also significantly shorter in the favipiravir arm (12 vs. 15 days). The mortality rate was also proportionally smaller at 5.7 percent in the favipiravir group vs. 8.3 percent in the standard of care group. Overall, the treatment was well-tolerated.

An interim analysis of the phase 3 COMET-ICE trial shows that treatment with monoclonal antibody VIR-7831 (GSK4182136) from Vir Biotechnology and GlaxoSmithKline (GSK) led to an 85 percent reduction in hospitalization or death when given early in patients with COVID-19. The trial is ongoing, and patients are continuing to be followed for up to 24 weeks. Given the positive findings from this trial, both Vir and GSK say they plan to submit an Emergency Use Authorization to the FDA for the drug. The global phase 3 portion of the COMET-ICE trial is currently evaluating the safety and efficacy of a single VIR-7831 infusion vs. placebo in up to 1,300 nonhospitalized participants with COVID-19.

COVID-19 Vaccines:

A laboratory study of 20 serum samples from 15 patients with COVID-19 suggests the Pfizer/BioNTech COVID-19 vaccine is effective against the emerging Brazilian SARS-CoV-2 variant. The study, conducted at the University of Texas Medical Branch, used serum samples from patients in the companies’ late-stage vaccine trial. According to the findings, the two-dose vaccine generated neutralization against both the Brazilian and UK strains that was similar to that seen against the original SARS-CoV-2 virus. Robust neutralization was also observed against the South African variant but at a lower rate than against the other variants. Since the study was conducted in a lab, researchers are still unsure how well the findings may generalize to the real-world setting.

Meanwhile, Pfizer announced it will enroll up to 4,000 healthy pregnant adult women in placebo-controlled COVID-19 vaccine trials to study if the vaccine is safe and effective in this population. Only women who are 24 to 34 weeks into their pregnancy will be eligible for enrollment. In addition to safety and efficacy assessments, researchers will also examine whether protective antibodies are transferred from the mother to the child. So far, Pfizer has only tested the vaccine in a development study using animals, but the company found no evidence of reproductive problems in these models. The company says it doesn’t expect to have data available from the human clinical trial for another six months.

A recent report suggests preliminary study data show AstraZeneca’s COVID-19 vaccine is effective against the P.1 SARS-CoV-2 strain, a coronavirus variant first detected in Brazil. AstraZeneca has not confirmed this report, nor have efficacy or safety data been released from this study. Last November, a combined interim analysis of data from a phase 2/3 trial in the UK and a phase 3 trial in Brazil found that the company’s COVID-19 vaccine AZD1222 was approximately 70 percent effective against infection. Additional analyses found the vaccine had a similar efficacy rate against the UK variant, B.1.1.7, but provided only minimal protection against mild-to-moderate disease from the South African B.1.351 strain. AstraZeneca has previously said it is working to update its vaccine to target new and emerging variants. The company hopes to have the new vaccine version ready by this fall.

Phase 3 trials have launched in Cuba to study the country’s COVID-19 vaccine candidate Soberana 2, which was developed by state-run Finlay Vaccine Institute. Cuba has already started recruiting for the planned 44,000-person trial in Havana. All trial volunteers must be between 19 and 80 years of age. Participants will receive two doses of the vaccine, and some participants will also receive a third booster vaccine dose with a different Cuban vaccine candidate. Researchers plan to complete the trial in November, and final results should be available in January of next year. Once the results are announced, Cuba plans to also launch late-stage trials of the COVID-19 vaccine in Iran. Cuba says it will vaccinate its entire 11 million population, pending vaccine approval.

VBI Vaccines has initiated enrollment of healthy volunteers in an adaptive phase 1/2 clinical trial studying its enveloped virus-like particle COVID-19 vaccine VBI-2902. Primary endpoints of the trial include safety, tolerability and immunogenicity. In the phase 1 portion, 60 healthy adults between 18 and 54 years of age will receive the two-dose regimen. The initial data from this portion of the study is expected by the end of the second quarter. In the phase 2 dose-escalation portion of the study, researchers will evaluate one- and two-dose vaccine regimens. The phase 2 study will be conducted at nine Canadian sites and will stratify people by age (18 to 54, 55 to 65, and 65 and older).

Johnson & Johnson’s (J&J) one-shot COVID-19 vaccine has received an interim authorization from Health Canada, which allows the vaccine to be used in the country to prevent COVID-19 in adults. The decision to clear the vaccine was made based on phase 3 trial data. The 43,783-participant trial showed the J&J shot was 85 percent effective for preventing severe COVID-19. Also, the vaccine reduced the risk of hospitalization and death 28 days following inoculation. The J&J vaccine features several advantages over other approved vaccines, such as those from Moderna and Pfizer/BioNTech, as it can be shipped at common refrigerator temperatures. The vaccine can also be stored for three months in common refrigerator temperatures and up to two years if kept at -4 degrees Fahrenheit. J&J recently announced that it expects to produce up to 10 million doses of its vaccine for Canada by the end of the third quarter.

A new phase 3 study in Brazil suggests Sinovac’s CoronaVac vaccine may not be effective against the newly identified coronavirus variant from Brazil. The study examined the effectiveness of the vaccine in blood plasma samples from eight vaccinated patients. In the study, the researchers found the Brazilian variant evades protection generated by CoronaVac. The studied plasma samples featured six times less neutralizing capacity against the new strain compared with strains that emerged from the UK and South Africa. Samples from patients who received a booster shot with CoronaVac also showed no signs of neutralization against the Brazilian variant at five months.

Moderna has started to dose trial participants with a modified version of its COVID-19 vaccine in an ongoing phase 2 study to see if the vaccine offers protection against the South African coronavirus variant. The trial is currently on track to enroll 60 participants who have already received a shot of Moderna’s COVID-19 vaccine. Participants will receive a booster that has been specifically designed to target the South African variant or a new multivalent vaccine candidate developed by the company to target the original strain and the new variant.