Pfizer And BioNTech Choose Lead MRNA Vaccine Candidate Against COVID-19 And Commence Pivotal Phase 2/3 Global Study
Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced the start of a global (except for China) Phase 2/3 safety and efficacy clinical study to evaluate a single nucleoside-modified messenger RNA (modRNA) candidate from their BNT162 mRNA-based vaccine program against SARS-CoV-2.
After extensive review of preclinical and clinical data from Phase 1/2 clinical trials, and in consultation with the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER) and other global regulators, Pfizer and BioNTech have chosen to advance their BNT162b2 vaccine candidate into the Phase 2/3 study, at a 30 µg dose level in a 2 dose regimen. BNT162b2, which recently received U.S. Food and Drug Administration (FDA) Fast Track designation, encodes an optimized SARS-CoV-2 full length spike glycoprotein (S), which is the target of virus neutralizing antibodies.
"Our selection of the BNT162b2 vaccine candidate and its advancement into a Phase 2/3 study are the culmination of an extensive, collaborative and unprecedented R&D program involving Pfizer, BioNTech, clinical investigators, and study participants with a singular focus of developing a safe and effective COVID-19 RNA vaccine. The Phase 2/3 study protocol follows all the U.S. Food and Drug Administration (FDA) guidance on clinical trial design for COVID-19 vaccine studies," said Kathrin U. Jansen, Ph.D., Senior Vice President and Head of Vaccine Research & Development, Pfizer. "The initiation of the Phase 2/3 trial is a major step forward in our progress toward providing a potential vaccine to help fight the ongoing COVID-19 pandemic, and we look forward to generating additional data as the program progresses."
"Today, we are starting our late-stage global study, which will include up to 30,000 participants. We selected BNT162b2 as our lead candidate for this Phase 2/3 trial upon diligent evaluation of the totality of the data generated so far. This decision reflects our primary goal to bring a well-tolerated, highly effective vaccine to the market as quickly as possible, while we will continue to evaluate our other vaccine candidates as part of a differentiated COVID-19 vaccine portfolio," said Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "Many steps have been taken towards this important milestone and we would like to thank all those involved for their extraordinary commitment."
About the BNT162b2 Candidate
During preclinical and clinical studies of four BNT162 RNA vaccine candidates, BNT162b1 and BNT162b2 emerged as strong candidates based on assessments of safety and immune response. Pfizer and BioNTech selected BNT162b2 as the candidate to progress to a Phase 2/3 study based on the totality of available data from our preclinical and clinical studies, including select immune response and tolerability parameters.
In the preclinical studies, BNT162b1 and BNT162b2 candidates induced favorable viral antigen specific CD4+ and CD8+T cell responses, high levels of neutralizing antibody in various animal species, and beneficial protective effects in a primate SARS-CoV-2 challenge model.
Preliminary clinical Phase 1/2 data from nearly 120 patients demonstrated a favorable overall tolerability profile for BNT162b2, as compared to BNT162b1, with generally mild to moderate and transient (1-2 days) systemic events, such as fever, fatigue and chills and no serious adverse events. Two 30 µg doses of BNT162b2 elicited neutralizing geometric mean titers (GMTs) generally similar to the GMTs that were elicited by the BNT162b1 vaccine candidate, as reflected in data the companies have previously posted on a preprint server. In older adults (65-85 years of age), two 30 µg doses, spaced three weeks apart, elicited a neutralizing antibody GMT higher than the GMT in a panel of 38 sera from subjects who had contracted SARS-CoV-2. BNT162b2 vaccinated human participants displayed a favorable breadth of epitopes recognized in T cell responses specific to the SARS-CoV-2 antigen, as compared to the BNT162b1 candidate. BNT162b2 demonstrated concurrent induction of high magnitude CD4+ and CD8+ T cell responses. BNT162b2 elicited T cell responses against the receptor binding domain (RBD) and against the remainder of the spike glycoprotein that is not contained in the BNT162b1 vaccine candidate. The companies believe that immune recognition of more spike T cell epitopes may have the potential to generate more consistent responses across diverse populations and in older adults.
The companies are continuing to collect data from the Phase 1/2 trials for all four vaccine candidates and expect to submit data on BNT162b2 for peer review and potential publication in the near future. In keeping with their commitment to transparency, the companies intend to also post the manuscript on a preprint server at that time.