COVID-19 Drug Research Roundup

COVID-19 Vaccines:

Pfizer/BioNTech’s BNT162b2 vaccine received a much-anticipated Emergency Use Authorization (EUA) from the FDA on Friday after an agency advisory committee gave the thumbs up on Thursday. BNT162b2 is the first COVID-19 vaccine authorized in the U.S., following authorization by Canada, the UK, Bahrain and Saudi Arabia.

Data from a pooled analysis of phase 3 trials show AstraZeneca’s and the University of Oxford’s COVID-19 vaccine AZD1222 is 70.4 percent effective for at least 14 days after the second injection. This compares with previously reported data showing a 90 percent efficacy with a one-and-a-half-dose regimen and a 62 percent efficacy with a two-dose regimen. In Kenya, a phase 1 trial to test the safety of the vaccine is under way.

In another effort, AstraZeneca has said it will partner with Russia’s Gamaleya Institute, makers of the controversial Sputnik V vaccine, to determine whether a combination of the two companies’ drugs can increase efficacy. The plan calls for giving an initial dose of one vaccine and following it up with a booster dose of the other, which researchers think will help avoid vector-immunity.

India has reportedly rejected AstraZeneca’s COVID-19 vaccine with claims that the vaccine candidate had inadequate safety and efficacy data to support its approval. In contrast, regulators in the UK say they plan to review all of the company’s vaccine data to identify an appropriate dosing regimen.

In a major setback, Sanofi and GlaxoSmithKline announced they would delay joint development of their adjuvanted COVID-19 vaccine after it failed in testing among adults older than 49. The collaborators had hoped to begin phase 3 clinical trials this month but are now planning to begin a phase 2b study of a revised vaccine in February.

A COVID-19 vaccine candidate developed by the Beijing Institute of Biological Products, a subsidiary of China’s Sinopharm, is reportedly 86 percent effective against COVID-19 infection. There were no serious safety concerns associated with the vaccine.

The UK is planning to conduct pilot trials that will investigate a regimen consisting of two different COVID-19 vaccines to determine whether a “mix-and-match” vaccination strategy offers better protection against infection with SARS-CoV-2. The studies, which will investigate the use of AstraZeneca’s AZD1222 and Pfizer/BioNTech’s BNT162b2, are expected to begin in January, pending approval of the AstraZeneca candidate.

Moderna has started a phase 2/3 study of its COVID-19 vaccine in adolescents younger than 18 and older than 12 years of age. The trial is being conducted with the Biomedical Advanced Research and Development Authority and will recruit up to 3,000 participants in the U.S. Endpoints include safety and reactogenicity. The company says it will seek to publicize data from the trial before the start of the 2021-2022 school year. The new trial from Moderna follows the company’s recent announcement that its two-dose COVID-19 vaccine was associated with a 95 percent efficacy rate in adults.

Johnson & Johnson has cut enrollment from 60,000 to 40,000 for its global phase 3 ENSEMBLE 1 trial evaluating COVID-19 vaccine candidate JNJ-78436735 as a single-dose regimen. The company made the decision based on how widespread the virus has become, with the drugmaker concluding that a smaller trial makes the most sense since more participants will contract the disease.

Gennova Biopharmaceuticals has been granted conditional permission by the Drugs Controller General of India to conduct a phase 1/2 trial of mRNA COVID-19 vaccine candidate HGCO19.

Inovio has said it has dosed the first participant in the phase 2 portion of the company’s phase 2/3 trial of COVID-19 vaccine candidate INO-4800. The company plans to enroll 400 adults across 17 U.S. sites to evaluate the candidate’s safety, tolerability and immunogenicity when delivered as a two-dose regimen. Inovio reached a deal with Japan’s Kaneka for the manufacture of INO-4800, which the company says will help them produce “hundreds of millions” of vaccine doses for global distribution. Thermo Fisher Scientific also struck a deal with Inovio in September to manufacture more than 100 million doses annually. Additional distribution deals have been made with Richter-Helm BioLogics and Ology Bioservices.

A phase 1 study from China’s Clover Biopharmaceuticals showed that the company’s COVID-19 S Trimer vaccine candidate generated strong immune responses in 150 adult and elderly participants. The randomized study evaluated the candidate’s safety, reactogenicity and immunogenicity when combined with an adjuvant from Glaxo-SmithKline or Dynavax Technologies. According to Clover, antibodies were induced in 100 percent of study participants. Clover currently plans to run a global phase 2/3 study using the GlaxoSmithKline adjuvant system and is preparing for a separate pivotal trial studying its vaccine candidate with Dynavax’s adjuvant.

COVID-19 Therapies:

A clinical trial conducted by the International Center for Diarrheal Disease Research in Bangladesh has found that anti-parasitic agent ivermectin was significantly better than a combination regimen consisting of ivermectin and doxycycline for treating COVID-19. In the study, 77 percent of patients with COVID-19 who received ivermectin monotherapy for five days experienced viral clearance after 14 days compared with 61 percent of patients in the combination group and 39 percent of patients in the placebo arm. Around 18 percent of patients treated with ivermectin alone experienced viral clearance by the third day compared with only 3 percent of patients who received ivermectin plus doxycycline and a placebo. At seven days, 50 percent of patients treated with only ivermectin had viral clearance vs. 30 percent of patients in the combination therapy arm and 13 percent in the placebo group.

UnitedHealth and Eli Lilly have teamed up to launch a pragmatic study of COVID-19 antibody treatment bamlanivimab (LY-CoV555), a therapy which had previously received an EUA from the FDA. Researchers will examine the safety and efficacy of the treatment in a diverse patient population. The trial plans to enroll up to half a million participants in the UnitedHealthcare Medicare Advantage plan, including individuals at high risk of COVID-19, and at least 5,000 of the participants will receive bamlanivimab in real-life settings.

Questions remain regarding a COVID-19 combination treatment regimen comprising Eli Lilly’s rheumatoid arthritis drug Olumiant (baricitinib) and Gilead Sciences’ antiviral Veklury (remdesivir) after it received an EUA Nov. 19. While the combination treatment was deemed effective for reducing recovery time among patients with severe COVID-19 in the phase 3 ACTT-2 trial, it was also associated with serious side effects. The National Institutes of Health has recently announced that another study will be conducted with the dual-treatment approach at the end of November in hospitalized patients with COVID-19. This trial will compare baricitinib with remdesivir vs. remdesivir with dexamethasone. Additionally, Lilly is conducting a separate study of baricitinib with dexamethasone in hospitalized patients with COVID-19.