Pfizer and BioNTech on Wednesday announced that the most advanced of four COVID-19 vaccine candidates from their BNT162 mRNA-based vaccine programme, dubbed Project Lightspeed, has yielded positive early results in an ongoing Phase I/II study in the US. Data for the BNT162b1 candidate, which encodes an optimised SARS-CoV-2 receptor binding domain (RBD) antigen, is available online on the MedRxiv preprint manuscript server and is currently undergoing scientific peer-review for potential publication, the companies noted.
"These preliminary data are encouraging in that they provide an initial signal that BNT162b1 targeting the RBD SARS-CoV-2 is able to produce neutralising antibody responses in humans at or above the levels observed in convalescent sera – and that it does so at relatively low dose levels," commented Ugur Sahin, chief executive at BioNTech.
The randomised trial is evaluating the safety, tolerability and immunogenicity of escalating dose levels of BNT162b1. The initial portion of the study included 45 healthy adults with a mean age of 35.4 years, ranging from 19 to 54. Preliminary data analysed 24 subjects who were administered two injections of BNT162b1 at doses of 10 mcg and 30 mcg, 12 who received a single injection of 100 mcg, and nine who were given placebo. Aside from patients in the 100-mcg group, who received a single injection, the other participants received two doses, given 21 days apart.
Results showed that at day 28, or seven days after the second dose, all those who received 10 mcg or 30 mcg of BNT162b1 had significantly elevated RBD-binding IgG antibodies, with geometric mean concentrations (GMCs) of 4813 units/mL and 27,872 units/mL, respectively. Pfizer and BioNTech noted that these concentrations are 8- and 46.3-times the GMC of 602 units/mL in a panel of 38 sera from convalescent patients who had contracted SARS-CoV-2. Similarly, all subjects in the 10- and 30-mcg dose groups had SARS-CoV-2 neutralising antibodies with respective geometric mean titers (GMTs) of 168 and 267, which are 1.8- and 2.8-times the GMT of the convalescent serum panel.
"Robust immunogenicity was observed after vaccination with BNT162b1," the authors state in the MedRxiv paper. They noted "assuming that neutralisation titers induced by natural infection provide protection from COVID-19 disease, comparing vaccine-induced SARS-CoV-2 neutralisation titers to those from sera of convalescent humans quantifies the magnitude of the vaccine-elicited response and the vaccine's potential to provide protection."
Meanwhile, at day 21 after a single injection, the 12 subjects who received 100 mcg of BNT162b1 had an RBD-binding IgG GMC of 1778 units/mL and a SARS-CoV neutralising GMT of 33, which are 3- and 0.35-times the GMC and GMT of the convalescent serum panel, respectively.
In terms of safety, local reactions and systemic events after administration with 10 mcg and 30 mcg of BNT162b1 were dose-dependent, generally mild-to-moderate, and transient. Following the second injection, 75% of the patients who received the 30-mcg dose reported fever of 38.0 °C or more, which the authors said generally resolved within one day of onset. Still, Sahin indicated "we believe the dose could be lower than 30 mcg, if supported by sufficient data." Besides the 10-mcg dose being tested, he said the company is also evaluating one at 20 mcg, in the hopes that these lower doses will reduce side effects.
The most common local reaction was injection-site pain, which was typically mild-to-moderate, except in one case, where the pain was severe in a person who received the single 100-mcg injection. Pfizer and BioNTech noted that as higher number of people in 100-mcg cohort experienced local reactions and systemic events, with no significant increases in immune response compared to the 30-mcg dose level, they were not given a second injection. Meanwhile, no serious adverse events were reported.
Later stage testing possibly set to begin in July
Results from early-stage testing of the three other potential COVID-19 vaccines have yet to be published. Pfizer and BioNTech stated that further data from the ongoing trial will enable selection of a lead candidate and dose level for an eventual global Phase IIb/III study that could begin as early as this month and potentially involve up to 30,000 healthy participants.
The companies also indicated that "efforts to manufacture the leading candidates, at risk, are gearing up," and if ongoing studies are successful and the vaccine candidate is approved, they expect to produce up to 100 million doses by the end of 2020 and potentially more than 1.2 billion doses by the end of 2021. Pfizer and BioNTech would then jointly distribute the vaccine worldwide, excluding China, where BioNTech is partnered with Fosun Pharma on BNT162.
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