Pfizer and BioNTech may have a strong pedigree in the mRNA vaccine game, but, when it comes to flu, they’ve run up against the same problem as their peers—neutralizing influenza strain B.
The two companies have been testing a combination flu and COVID-19 vaccine in a phase 3 trial. While the candidate did demonstrate sufficient immunogenicity against SARS-CoV-2 when compared to the companies’ own approved COVID-19 vaccine Comirnaty, it failed the trial’s other primary endpoint of triggering an immune response against both influenza strains A and B when compared to an unnamed approved flu shot.
“Compared to a licensed influenza vaccine, the [trivalent] formulation was noteworthy for eliciting robust influenza A responses, including a continued trend of higher influenza A responses versus a licensed influenza vaccine, while it showed lower geometric mean titers and seroconversion against the influenza B strain,” the two companies noted.
The study enrolled more than 8,000 adults ages 18 to 64, and the companies said no safety signals related to its combo vaccine were identified in an ongoing safety data review.
Pfizer and BioNTech are now “evaluating adjustments” to the combo candidate, which consists of Comirnaty and an mRNA flu vaccine that Pfizer has been working on.
“We are dedicated to developing combination vaccines which provide broader protection against multiple respiratory diseases,” BioNTech CEO Ugur Sahin, M.D., said in the release.
“The insights gained from this combination vaccine trial are highly valuable and will play a crucial role in guiding the further development of Pfizer’s and our combination vaccine program against influenza and COVID-19,” Sahin added. “We are committed to drawing on our experience in developing mRNA-based vaccine candidates against multiple antigens and believe we can successfully accomplish this task in collaboration with our partner Pfizer.”
Annaliesa Anderson, Ph.D., senior vice president and head of vaccine R&D at Pfizer, said the Big Pharma “remains optimistic” about the combo vaccine while it is “evaluating the next steps.”
Perhaps the companies can take some comfort from the fact that their mRNA peers have also struggled to tackle influenza strain B. A previous version of Moderna’s mRNA-1010 vaccine failed to meet the noninferiority threshold for two influenza B strains a year ago. Moderna was later able to bring a new formulation into the clinic that overcame this setback.
More recently, CureVac and GSK’s mRNA flu vaccine came up short against “historically challenging” B strains, leading the partners to work on “targeted optimizations” to improve the vaccine’s protection against these strains.
Meanwhile, Sanofi’s executives were so disheartened by the failure of their own candidate to neutralize B strains that they proclaimed last year that the first generation of mRNA vaccines for flu “will not win.”
Judging by Pfizer’s other piece of news today, Sanofi may be proved right. In this morning’s release, Pfizer also revealed that a phase 2 trial of its next-gen trivalent mRNA flu formulations “elicited robust influenza A responses and B responses, including continued trend of higher influenza A responses versus a licensed influenza vaccine” in adults ages 18 to 64.
The Big Pharma didn’t go into more detail and said a top-line readout from the trial for adults ages 65 years and over would only be unveiled “at a later date.”
A phase 3 trial of Pfizer’s original quadrivalent mRNA influenza candidate already secured success against B strains among people younger than 65, the pharma pointed out in today’s release, but couldn’t manage the same feat in older patients.