Pfizer, BioNTech's mRNA combo shot fails against influenza B

Pfizer and BioNTech, renowned for their achievements in the mRNA vaccine space, have encountered challenges while developing a combination flu and COVID-19 vaccine. In a recent phase 3 trial, their candidate demonstrated satisfactory immunogenicity against SARS-CoV-2 when compared to their approved COVID-19 vaccine, Comirnaty. However, it did not meet its primary goal of generating an immune response against both influenza A and B strains when pitted against an existing flu vaccine.

The trial, which included over 8,000 participants aged 18 to 64, indicated robust responses to influenza A but fell short in terms of geometric mean titers and seroconversion rates against influenza B. Notably, no safety concerns were flagged in the ongoing review of the combination vaccine, which merges Comirnaty with an mRNA flu vaccine that Pfizer has been developing.

Both companies are now reassessing their approach to the combination vaccine. Ugur Sahin, M.D., CEO of BioNTech, emphasized their commitment to creating vaccines offering comprehensive protection against multiple respiratory illnesses. He noted that insights from the current trial would significantly inform the future development of their combined vaccine program. Sahin expressed confidence in leveraging their mRNA vaccine development experience in partnership with Pfizer to achieve this objective.

Annaliesa Anderson, Ph.D., Senior Vice President and Head of Vaccine R&D at Pfizer, shared a similar sentiment. She described the company’s ongoing optimism about their combination vaccine and mentioned that they are currently contemplating the next steps.

This challenge with influenza strain B is not unique to Pfizer and BioNTech. Moderna faced similar issues with an earlier version of its mRNA-1010 vaccine, which failed to meet the noninferiority threshold for two influenza B strains. Moderna subsequently developed a new formulation that addressed this issue. Similarly, CureVac and GSK's mRNA flu vaccine also struggled with B strains, prompting the partners to make targeted optimizations for better protection.

Sanofi has also experienced setbacks, with its executives expressing skepticism about the first generation of mRNA flu vaccines' ability to neutralize B strains. They even declared last year that these initial mRNA flu vaccines "will not win."

Reflecting on Pfizer’s other announcements, it seems Sanofi’s prediction might hold some weight. Pfizer disclosed that a phase 2 trial of its next-generation trivalent mRNA flu formulations produced strong responses against both influenza A and B strains in adults aged 18 to 64. However, details were sparse, and a top-line readout for older adults is expected at a later date.

Pfizer did highlight that a phase 3 trial of their original quadrivalent mRNA influenza candidate had succeeded against B strains in people under 65 but failed to replicate this success in older patients. This ongoing challenge emphasizes the complexity of developing a comprehensive mRNA vaccine that can effectively target all relevant strains of both flu and COVID-19.

In summary, Pfizer and BioNTech, despite their considerable expertise in mRNA vaccines, are facing significant hurdles in creating a combined flu and COVID-19 vaccine that effectively neutralizes both influenza A and B strains. Their experiences mirror those of their peers in the mRNA vaccine field, suggesting that more time and research are needed to overcome these challenges.