The FDA plans to post their reviews and data supporting an Emergency Use Authorization for COVID-19 vaccines. The FDA is working on a meeting during second week of December for its vaccines advisory committee to discuss COVID-19 vaccines from Pfizer-BioNTech and Moderna. Peter Marks, the head of the FDA’s Center for Biologics Evaluation and Research said the FDA review may takes weeks.
Pfizer and BioNTech are evaluating BNT162b2 in a Pfizer funded, 44,000 patient, Phase II/III trial (NCT04368728) BNT162b2 will be administered as two 30 mcg immunizations given 21-days apart. The trial was expanded from its original 30,000 patients, in September 2020, to allow the vaccine to be tested in a larger more diverse population, including adolescents as young as 16 years of age and people with HIV, Hepatitis C, and Hepatitis B. Pfizer and BioNTech announced final efficacy results from the Phase III trial on 11/18/2020. BNT162b2 efficacy was found to be 95% in 43,661 patients 28 days after the first dose, 7 days after the second dose. A total of 170 cases of COVID-19 developed in the study population with eight in the vaccine group and 164 in the placebo group. There were ten cases of serious COVID-19 with one in the vaccine group and nine in the placebo group. About 42% of participants have diverse backgrounds, and 41% are 56-85 years of age. Efficacy was consistent across age, gender, race and ethnicity demographics. The observed efficacy in adults over 65 years of age was over 94%. The only ADR that were Grade 3 (severe) and occurred in at least 2% of patients was fatigue (3.8%) and headache (2%). Older adults reported fewer and milder adverse events following vaccination. Pfizer and BioNtech requested an emergency use authorization (EUA) for BNT162b2 to prevent COVID-19 on 11/20/2020 and will have 50 million vaccine doses available in 2020 and up to 1.3 billion doses in 2021.
Results from the 500 patient, Phase II portion of a 12,390 patient, Phase II/III trial found that AZ’s AZD1222 elicited similar antibody titers in all age groups. The vaccine was well tolerated and older patients had fewer adverse reaction than younger patients.
In a 743 patient Phase I/II trial (NCT04352608), Sinovac COVID-19 vaccine, CoronaVac, elicited neutralizing antibodies four weeks after two doses of the vaccine given 14 days apart. Based on results from the trial a 3 mcg dose was chosen for Phase III trials.
COVID-19 Monoclonal Antibodies
NIH did not find enough evidence to recommend for or against use of bamlanivimab for the treatment of outpatients with mild to moderate COVID-19. Due to the limited supply, use of the drug should be restricted to patients at the highest risk to progress to severe COVID-19. Hospitalized patients should not receive bamlanivimab outside of a clinical trial.
COVID-19 Antiviral and Anti-inflammatory
The FDA granted an EUA for the combination of baricitinib (Olumiant. Lilly) plus remdesivir (Veklury, Gilead) to treat hospitalized adults and pediatric patients two years of age or older, with COVID-19 and who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The approval was based on the 29-day, 1,034 patient, Phase III, ACTT 2 trial (NCT04401579), where baricitinib added to remdesivir reduced the time to hospital discharge by one day (7 vs 8 days) compared to remdesivir alone in hospitalized patients with COVID-19. ACTT 2 was sponsored by NIAID. The largest effect was seen in patients requiring supplemental oxygen or high-flow oxygen/non-invasive ventilation.