Pfizer (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) recently reported preliminary data from the most advanced of four investigational vaccine candidates from their BNT162 mRNA-based vaccine program known as Project Lightspeed targeting SARS-CoV-2, the virus causing the current global pandemic. The BNT162 program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target antigen. In a press release, Pfizer announced that the manuscript describing the preliminary clinical data for the nucleoside-modified messenger RNA (modRNA) candidate, BNT162b1, which encodes an optimized SARS-CoV-2 receptor binding domain (RBD) antigen, is now available for review on the medRxiv preprint server while it concurrently undergoes scientific peer-review for potential publication.
Upon first observation of preliminary data demonstrates that BNT162b1 can be administered in a dose that in fact was well tolerated and generated dose dependent immunogenicity, as measured by RBD-binding igG concentrations and SARS-CoV-2 neutralizing antibody titers.
Kathrin U. Jansen, PhD, Senior Vice President and Head of Vaccine Research & Development at Pfizer was encouraged, commenting that the target candidate BNT162b1 (one of the four under investigation) evidence “positive preliminary, topline findings.” Ugur Sahin, MD, CEO and Co-founder of BioNTech, reported, “These preliminary data are encouraging in that they provide an initial signal that BNT162b1 targeting the RBD SARS-CoV-2 is able to produce neutralizing antibody responses in humans at or above the levels observed in the convalescent sera—and it does so at relatively low dose levels. We look forward to providing further data updates on BTN162b1.”
This ongoing U.S. Phase 1/2 randomized, placebo-controlled, observed-blinded study is evaluating the safety, tolerability and immunogenicity of escalating dose levels of BNT162b1. The initial part of the study included 45 healthy adults 18 to 55 years of age. Preliminary data for BNT162b1 was evaluated for 24 subjects who received two injections of 10 µg and 30 µg, 12 subjects who received a single injection of 100 µg, and 9 subjects who received 2 doses of placebo control.
Results Thus Far
Pfizer reports that participants receiving two doses, 21 days apart of placebo 10 µ g or 30 µg of BNT162b1, or received a single dose of 100 µg of the vaccine candidate. Because of a strong booster effect, the highest neutralizing titers were observed seven days after the second dose of 10 µg or 30 ug on day 28 after vaccination. The neutralizing GMTs were 168 and 267 for the 10 ug and 30 µg dose levels, respective, corresponding to 1.8- and 2.8-times the neutralizing GMT of 94 observed in panel of 38 sera from subjects who had contracted SARS-CoV-2.
In all 24 subjects who received 2 vaccinations at 10 ug and 30 ug dose levels, of BNT162b1, elevation of RBD-binding IgG concentrations was observed after the second injection with respective GMCs of 4,813 and 27,872 units/ml at day 28, seven days after immunization. These concentrations are 8- and 46.3- times the GMC of 602 units/ml in a panel of 38 sera from subjects who had contracted SARS-CoV-2.
At day 21 after a single injection, the 12 subjects who received 100 ug of BNT162b1 had an RBD-binding IgG GMC of 1,778 units/ml and a SARS-CoV neutralizing GMT of 33, which are 3 times and 0.35 times, respectively, the GMC and GMT of the convalescent serum panel.
At the 10 µg or 30 µg dose levels, adverse reactions, including low grade fever, were more common after the second dose than the first dose. Following dose 2, 8.3% of the participants who received 10 ug and 75.0% of participants who received 30 µg BNT162b1 reported fever ≥ 38.0°C. Local reactions and systemic events after injections with 10 µg and 30 µg of BTN162b1 were dose-dependent, generally mild to moderate and transient. The most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 µg dose, which was severe. No serious adverse events were reported. Given higher numbers of subjects experiencing local reactions and systemic events after a single 100 µg dose with no significant increases in immunogenicity compared to the 30 ug dose level, the 12 participants in the 100 µ group were not administered a second dose.
This preliminary date along with other preclinical and clinical data being generated will be used by both partners to determine a dose level and select among multiple vaccine candidates to seek to progress to a large, global phase 2b/3 safety and efficacy trial. That trial can involve up to 30,000 healthy participants and is anticipated to commence in late July 2020 assuming regulatory approval. This preliminary data has been submitted for potential publication in a peer-reviewed journal and is now available on an online preprint manuscript server.
What if Approved?
Should the vaccine product be approved, the companies plan on manufacturing up to 100 million doses by the end of 2020 and potentially over 1.2 billion doses by the of 2021. In this rosy scenario, both BioNTech and Pfizer would work jointly to distribute the vaccine product excluding China where Fosun Pharma has BNT162 for both clinical development and commercialization.