Pfizer and BioNTech SE announced positive preliminary results from the phase 1/2 study evaluating the safety, tolerability, and immunogenicity of escalating doses of the vaccine candidate BNT162b1 against coronavirus disease 2019 (COVID-19).
BNT162b1 is an experimental nucleoside-modified messenger RNA (modRNA) vaccine that encodes an optimized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein receptor binding domain (RBD) antigen. The initial part of the ongoing, randomized, placebo-controlled study included 45 healthy adults aged 18 to 55 years, of which 24 individuals received 2 doses (21 days apart) of 10mcg or 30mcg of BNT162b1, 12 participants received a single injection of BNT162b1 100mcg, and 9 received 2 doses of placebo.
Preliminary data showed that 7 days after the second dose, patients who received BNT162b1 10mcg or 30mcg reported the highest neutralizing geometric mean antibody titers (GMT) (168 and 267, respectively), corresponding to 1.8- and 2.8-times that observed from a panel of 38 convalescent human serology samples obtained from patients who had confirmed SARS-CoV-2 infection.
Additionally, both doses of 10mcg and 30mcg led to elevations of RBD-binding IgG concentrations with geometric mean concentrations (GMCs) of 4813 and 27872 units/mL, respectively, at day 28 compared with a GMC of 602 units/mL in a panel of 38 sera from individuals who had contracted SARS-CoV-2.
Among patients who received a single dose of BNT162b1 100mcg, a neutralizing GMT of 33 and an RBD-binding IgG GMC of 1778 units/mL were observed on day 28. These results were found to be 0.35-times and 3-times that of the GMT and GMC of a panel of COVID-19 convalescent human sera, respectively.
“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 convalescent sera – and that it does so at relatively low dose levels,” said Ugur Sahin, MD, CEO and Co-founder of BioNTech.
Regarding safety, the most common adverse reactions observed for BNT162b1 10mcg or 30mcg were low grade fever, as well as local reactions and systemic events which were dose-dependent, generally mild to moderate and transient. Patients who received BNT162b1 100mcg reported a higher frequency of local reactions and systemic events. There were no serious adverse events reported.
“We are encouraged by the clinical data of BNT162b1, 1 of 4 mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings,” said Kathrin U. Jansen, PhD, Senior Vice President and Head of Vaccine Research & Development, Pfizer.
A phase 2b/3 trial is expected to begin in late July 2020 after an appropriate dose level is determined and the most viable vaccine candidate is selected. According to the Companies, manufacturing efforts are also increasing to keep up with potential demand. If approved, the Companies expect to produce up to 100 million doses by the end of 2020 and possibly more than 1.2 billion doses by the end of 2021.