COVID-19 Drug Research Roundup

COVID-19 Vaccines:

The European Medicines Agency (EMA) has granted AstraZeneca (AZ) conditional marketing authorization for its COVID-19 vaccine, making AZ’s vaccine the third approved by the agency for emergency use following the Pfizer/BioNTech and Moderna vaccines. The EMA based its decision on AZ trials in the UK and Brazil, which showed a nearly 60 percent efficacy rate.

Data from an interim analysis of Johnson and Johnson’s (J&J) one-shot COVID-19 vaccine trial show an overall efficacy rate of preventing moderate-to-severe COVID-19 of 66 percent, with varying rates for trials geographically: in the U.S. (72 percent) and South Africa (57 percent). Latin American trials showed the same efficacy as the overall result. The J&J vaccine proved 85 percent effective at preventing severe cases of COVID-19. The company says it plans to apply to the FDA for Emergency Use Authorization within a week.

Pfizer says the COVID-19 vaccine it codeveloped with BioNTech neutralizes key mutations in the highly contagious UK and South African coronavirus strains. In vitro neutralization studies it conducted recently showed that the three key mutations in the South Africa strain did have a small impact on the vaccine, but not enough to worry the drugmaker, which said the findings, which have not yet been peer-reviewed, suggest it would not need to revamp its vaccine for the variant.

Novavax announced last week that interim results from a phase 3 UK trial showed its COVID-19 vaccine candidate, NVX-CoV2373, is 89.3 percent effective. But early results from a phase 2b study in South Africa that mostly involved cases of the COVID-19 variant identified in that country showed NVX-CoV2373 had only a 49 percent efficacy rate. For the 94 percent of participants in the South African trial who were HIV-negative, however, the efficacy increased to 60 percent.

Moderna is working on a booster for its authorized COVID-19 vaccine in an effort to increase the vaccine’s ability to protect against the recently discovered South African variant. The mRNA COVID-19 vaccine from Moderna appears to be slightly effective against the highly infectious South African strain, but its efficacy is better for the recent variant from the UK, according to newly released study data. While Moderna says it is moving toward testing its booster for the South Africa variant in a U.S. phase 1 trial, no plans have been developed to develop a booster for the UK variant. The Cambridge, Mass.-based company also launched a phase 1 trial in the summer to identify whether a third shot with its vaccine offers better efficacy than the currently authorized two-dose immunization protocol.

Japan is insisting on domestic COVID-19 vaccine clinical trials before vaccines can be used in the country. This requirement places further delays in vaccine rollout across the country and threatens the future of the Tokyo Olympics.

Canada’s Providence Therapeutics recently launched placebo-controlled human trials testing its mRNA COVID-19 vaccine candidate PTX-COVID19-B. The Toronto-based company recently bought a new 20,000-square-foot site in Calgary to produce its vaccine.

Medicago’s COVID-19 vaccine, which began clinical trials last July, is currently undergoing testing in phase 3 clinical trials. If successful, the company plans to apply for approval from Health Canada.

COVID-19 Therapies:

Regeneron’s monoclonal antibody cocktail REGN-COV2 significantly reduced medical visits by almost 50 percent among patients with COVID-19, according to interim clinical trial results. Only 3 percent of patients in the REGN-COV2 arm had a medically attended visit during the study’s follow-up period vs. 6 percent of patients in the placebo group. The antibody cocktail, which consists of casirivimab and imdevimab, was granted Emergency Use Authorization (EUA) in November for use in patients with mild-to-moderate COVID-19 over the age of 12. Interim data from an ongoing phase 3 trial also show that Regeneron’s REGEN-COV reduced infection rates by 50 percent and offered complete protection against symptomatic COVID-19. All 186 participants in the trial who received the 1,200-mg injected dose of the cocktail had complete protection from symptomatic disease, despite living with an infected person. In contrast, eight out of the 223 patients in the placebo group developed COVID-19-related symptoms. Regeneron says its recent trial findings may support an EUA for the therapy as a passive vaccine.

An antibody cocktail from Eli Lilly was found to reduce the risk of death and hospitalization by 70 percent in a phase 3 study of high-risk patients with mild-to-moderate COVID-19. The therapy is a combination of monoclonal antibodies bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016). In the late-stage, 1,035-patient trial, a total of 10 deaths were observed in the placebo group vs. no deaths in the active treatment group. There were also 26 hospitalizations in the placebo arm vs. 11 hospitalizations in the antibody arm. Overall, these data demonstrate that the antibody cocktail led to a 70 percent reduction in the risk of a COVID-19 hospitalization or death. Only bamlanivimab has received an EUA for high-risk patients with COVID-19, but the FDA is reviewing the trial data for Eli Lilly’s antibody cocktail for possible emergency approval in this patient population.

Recent lab tests suggest Regneron’s antibody cocktail is slightly effective against a newly discovered coronavirus variant from South Africa, while the activity of Eli Lilly’s antibody cocktail was inactive when tested against this new strain. The lab tests were conducted by a team of researchers from Columbia University, the National Institutes of Health and Regeneron. Findings from this lab-based study have not yet been peer-reviewed but were published on BioRxiv.

Merck has dropped its two COVID-19 vaccine candidates after clinical trial results showed subpar immune responses following inoculation. The company is switching its focus to MK-7110 and MK-4482, two investigational COVID-19 therapies. Ridgeback Bio is collaborating with Merck to study experimental antiviral MK-4482 in phase 2/3 trials. The initial efficacy data from this research are expected in the first quarter. Recombinant fusion protein MK-7110 has so far shown some promise against COVID-19, according to interim results from a phase 3 trial. This study found the drug candidate, which was obtained from Merck in a $425 million acquisition of OncoImmune, reduced the risk of death or respiratory failure by more than 50 percent among hospitalized patients with moderate-to-severe COVID-19. Full results from this trial are expected in the first quarter. Merck says it has signed a $356 million supply agreement with the U.S. government for 100,000 doses of the therapy, if it proves successful in this trial.

A 24-person phase 2b trial from Indian drugmaker Zydus Cadila Healthcare found that Desidustat increased red blood cell production and oxygen delivery to tissues in hospitalized patients with COVID-19 in Mexico. None of the patients treated with Desidustat required mechanical ventilation vs. 25 percent of patients who received standard of care alone. The company is evaluating Desidustat for anemias induced in two ongoing phase 3 trials.

A multi-institutional collaboration deal struck between Vir Biotechnology, Eli Lilly and GlaxoSmithKline has led to the launch of a new study to investigate Vir’s investigational monoclonal antibody VIR-7831 with Eli Lilly’s bamlanivimab as a treatment for low-risk patients with mild-to-moderate COVID-19. The ongoing BLAZE-4 study from Eli Lilly has been expanded to include Vir’s monoclonal antibody.

The Platform Randomized trial of INterventions against Covid-19 in older people (PRINCIPLE) trial from the University of Oxford has found that azithromycin and doxycycline are not particularly effective treatments for COVID-19. The study included 526 patients who received azithromycin and 798 patients who received doxycycline. Neither antibiotic provided a beneficial effect in people over 50 years of age with early COVID-19 who were treated at home.

Preliminary results of a phase 1b study show Sorrento Therapeutics’ human allogeneic adipose-derived mesenchymal stem-cell treatment was well-tolerated and improved symptoms in three patients with COVID-19. The patients in the study, all of whom had acute respiratory distress, were discharged from the hospital within a week after starting the infusion therapy. One of these patients had been hospitalized for three weeks, suggesting the infusion therapy could be a potentially effective option for patients with severe disease.

India’s trial approval committee has given the greenlight to Dr. Reddy’s Laboratories and Zuventus Healthcare to start phase 3 clinical trials studying injectable Aviptadil as a treatment for COVID-19. The trial on the repurposed erectile dysfunction treatment was granted approval by the Indian government on the condition that discharge criteria of patients from the ICU should be clearly defined in the trial protocol.

A large clinical trial backed by the National Institutes of Health shows that full-dose blood thinners reduced the need for vital organ support among 1,000 hospitalized patients with COVID-19. The trial, conducted in over 300 hospitals across five continents, found that full-dose heparin was better than lower doses in these patients.

Positive results from the Montreal Heart Institute’s COLCORONA trial show that oral colchicine lowered the risk of severe complications associated with COVID-19. The 4,500-patient randomized study was conducted in home settings across Canada, the U.S., Europe, South America and South Africa. Researchers found that the treatment reduced the risk of death or hospitalizations by 21 percent compared with placebo. However, the study results were only published via press release, indicating the data lack peer review and that the data were too limited to be considered statistically significant.

Daewoong Pharmaceutical has announced the start of a 1,000-person phase 3 trial studying Foistar, a TMPRSS2 inhibitor, as a preventative treatment for COVID-19.

The University of Oxford has announced it will soon accelerate its PRINCIPLE Trial studying Ivermectin as a potential COVID-19 treatment.