Vaccine Status 2020 [Pfizer-BioNTech]
Date posted: Sunday, November 15, 2020
Pfizer and BioNtech are collaborating to develop BNT162, a series of vaccine candidates for COVID-19. BNT162 was initially four candidates developed by BioNTech, two candidates consisting of nucleoside modified mRNA-based (modRNA), one of uridine containing mRNA-based (uRNA), and the fourth candidate of self-amplifying mRNA-based (saRNA).
Pre-clinical results of the modRNA candidate BNT162b2 posted to the pre-print server bioRxiv showed the vaccine had "protective anti-viral effects in rhesus macaques, with concomitant high neutralizing antibody titers and a TH1-biased cellular response in rhesus macaques and mice." The companies have selected BNT162b2 to move forward in a Phase 2/3 trial.
A Phase 1/2 trial in the US and Germany of 200 healthy participants between aged 18-55 years, with a vaccine dose range of 1 µg to 100 µg is currently recruiting (NCT04380701) as is a Phase 2/3 trial of about 32,000 healthy participants (NCT04368728) Pfizer and BioNTech are also planning a combined Phase 1/2 trial of 160 participants between 20-85 years old (NCT04588480).
On 9 November, Pfizer and BioNTech announced interim results by press release of 94 Phase 3 trial participants, which showed BNT162b2 was more than 90% effective in protecting participants who had never been infected with SARS-CoV-2 at 7 days after the second dose. Those results are backed up by Phase 1 data published in The New England Journal of Medicine showing similar immunogenicity between BNT162b1 and BNT162b2 but fewer adverse effects with BNT162b2. Another study of Phase 1/2 data for BNT162b1 was published in the journal Nature. Robust immunogenicity was seen after vaccination at all three doses (10 μg, 30 μg and 100 μg). Adverse events were elevated at the highest dose; therefore, participants did not receive a second dose at that level. Participants in Phase 1/2 trials who received two doses between 1 and 50 µg of BNT162b1 had "robust RBD-specific antibody, T-cell and favourable cytokine responses," according to a paper published in Nature on 30 September.
Pfizer and BioNTech have received FDA Fast Track designation for BNT162b1 and BNT162b2. BNT162b2 was selected to advance to a Phase 2/3 safety study "based on the totality of available data from our preclinical and clinical studies, including select immune response and tolerability parameters." The companies have asked the FDA to consider an expanded protocol for the Phase 3 trial to include up to 44,000 participants. EMA has initiated a rolling review of BNT162b2, which could accelerate approval of the candidate. Pfizer and BioNTech could be ready to file for an EUA in November and have the vaccine ready for use in December, according to the Wall Street Journal. In Australia, BNT162b2 received provisional determination from Australia’s Therapeutic Goods Administration (TGA), which is the first step on the road for approval for the vaccine in the country. BioNTech′s partner in China, Shanghai Fosun Pharmaceutical Group, announced it is seeking approval for BNT162b2 in China but would no longer be pursuing clinical trials for BNT162b1.
Institutions: Multiple study sites in Europe and North America
ExplanationPRECLINICAL TESTING: Scientists give the vaccine to animals such as mice or monkeys to see if it produces an immune response.
PHASE 1 SAFETY TRIALS: Scientists give the vaccine to a small number of people to test safety and dosage as well as to confirm that it stimulates the immune system.
PHASE 2 EXPANDED TRIALS: Scientists give the vaccine to hundreds of people split into groups, such as children and the elderly, to see if the vaccine acts differently in them. These trials further test the vaccine’s safety and ability to stimulate the immune system.
PHASE 3 EFFICACY TRIALS: Scientists give the vaccine to thousands of people and wait to see how many become infected, compared with volunteers who received a placebo. These trials can determine if the vaccine protects against the coronavirus. In June, the F.D.A. said that a coronavirus vaccine would have to protect at least 50% of vaccinated people to be considered effective. In addition, Phase 3 trials are large enough to reveal evidence of relatively rare side effects that might be missed in earlier studies.
PHASE 4 LICENCED: Regulators in each country review the trial results and decide whether to approve the vaccine or not. During a pandemic, a vaccine may receive emergency use authorization before getting formal approval. Once a vaccine is licensed, researchers continue to monitor people who receive it to make sure it’s safe and effective.