Pfizer and partner BioNTech on Monday said they have decided to advance the nucleoside-modified mRNA vaccine candidate BNT162b2 into Phase II/III testing. The vaccine, to be trialed at the 30-mcg dose as part of a two-dose regimen, encodes for an optimised SARS-CoV-2 full-length spike glycoprotein, which the companies said is targeted by virus neutralising antibodies.
The trial is expected to enroll up to 30,000 participants between 18 and 85 years of age who will be randomised to receive BNT162b2 or placebo., with study sites across the US and countries including Argentina, Brazil and Germany. Primary endpoints will be prevention of COVID-19 in those who have not been infected by SARS-CoV-2 prior to immunisation, and prevention of COVID-19 regardless of whether participants have previously been infected by the virus. Secondary goals include preventing severe COVID-19 disease in these groups.
BNT162b2 is one of four potential coronavirus vaccines being developed as part of the companies' BNT162 mRNA-based vaccine programme , and is different from the one they have recently reported data on. Earlier this month, Pfizer and BioNTech announced results from the US and German  cohorts of an ongoing Phase I/II study showing that BNT162b1, previously described by them as the "most advanced" of the four candidates in the programme, was able to stimulate immune responses in healthy volunteers. BNT162b1 encodes an optimised SARS-CoV-2 receptor binding domain (RBD) antigen.
Choice backed by totality of data
The companies indicated that BNT162b2 emerged as the lead candidate "based on the totality of available data from our preclinical and clinical studies, including select immune response and tolerability parameters." They noted that early Phase I/II data from nearly 120 patients suggested BNT162b2 had a better overall tolerability profile than BNT162b1, with typically mild-to-moderate and transient systemic events, such as fever, fatigue and chills, as well as no serious side effects.
In regards to potential efficacy, they said that compared to BNT162b1, participants who received BNT162b2 "displayed a favourable breadth of epitopes recognised in T-cell responses specific to the SARS-CoV-2 antigen." Specifically, BNT162b2 induced "high magnitude" CD4+ and CD8+ T-cell responses, and also triggered T-cell responses against both the RBD and the remainder of the spike glycoprotein that is not contained in the BNT162b1 candidate. "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 said. They also explained that in older adults aged 65 to 85 years old, the two 30-mcg doses, spaced three weeks apart, elicited neutralising antibody geometric mean titers (GMTs) higher than the GMT in a panel of 38 sera from subjects who had contracted SARS-CoV-2.
Recent US supply deal
If the Phase II/III trial proves successful, Pfizer and BioNTech expect to be ready to seek emergency-use authorisation or some form of regulatory approval as early as October. If authorisation or approval is obtained, the companies reiterated that their aim is to supply up to 100 million doses globally by the end of 2020, and approximately 1.3 billion doses by the end of next year. The US government recently agreed to pay nearly $2 billion  to secure 100 million doses of Pfizer and BioNTech's vaccine, with the possibility of acquiring 500 million more doses.
Meanwhile, the companies are continuing to collect data from the Phase I/II trials for all four vaccine candidates in their programme and said they expect to submit data on BNT162b2 for potential publication in the near future.
The news coincides with Moderna's announcement Monday that patient dosing started in the Phase III COVE study of its mRNA-based coronavirus vaccine candidate mRNA-1273. That study will recruit approximately 30,000 participants in the US to test mRNA-1273 at a dose of 100 mcg against placebo. Johnson & Johnson said earlier this month that it expects to begin  a late-stage clinical trial for a potential coronavirus vaccine in late September, ahead of schedule, while Phase II/III trials of AstraZeneca and the University of Oxford's vaccine AZD1222 are currently under way  in the UK, Brazil and South Africa, and are due to start in the US.