Pfizer/BioNTech Combination Flu/COVID-19 Shot Misses Key Primary Phase 3 Endpoint

The Pfizer/BioNTech investigational combination vaccine candidate against influenza and COVID-19 failed to meet one of the primary immunogenicity objectives in a phase 3 trial, the codevelopers announced today.¹

Although the vaccine delivered higher influenza A responses and comparable COVID-19 responses vs the study’s comparator vaccines, it did not meet noninferiority against the influenza B strain. Pfizer said it is assessing adjustments to the current formulation and will meet with health authorities to discuss the next steps.¹ The company was granted Fast Track designation for the double immunization by the FDA in December 2022.²

Results from the phase 1/2 clinical trials of the vaccine combination, announced in October 2023, demonstrated robust immune responses to both influenza A and influenza B, and SARS-CoV-2 strains in healthy vaccine candidates aged 18 to 64 years.³ In the phase 3 randomized, observer-blinded trial the companies evaluated the combined mRNA vaccine, consisting of Pfizer’s mRNA-based influenza candidate and the companies’ licensed COVID-19 vaccine, in 8000 healthy adults in the same age range. The combination shot was compared to a licensed influenza vaccine and the Pfizer/BioNTech licensed COVID-19 vaccine given at the same clinic visit, the company said.¹

For the primary immunogenicity objectives, the trial aimed to show that the antibody responses to influenza and to SARS-CoV-2 elicited by the combination vaccine were noninferior the individual licensed shots, considered to be standard of care. The comparison with a licensed flu vaccine showed strong responses against influenza A that trended higher than responses from the comparator vaccine. Geometric mean titers and seroconversion against the influenza B strain, were both lower. There have been no safety signals with the combined vaccine identified during an ongoing safety data review, according to Pfizer.¹

“We are encouraged by the robust immunogenicity we saw with our combination vaccine against influenza A, which was similar to what we had seen for our initial quadrivalent influenza vaccine where we saw superior relative vaccine efficacy against a comparator flu vaccine,” Annaliesa Anderson, PhD, Pfizer senior vice president and head, vaccine research and development said in the company release.¹ “We are committed to developing vaccines that will reduce the burden of respiratory diseases and believe that combination vaccines are the most efficient way to do this. Today’s results provide insight and direction towards achieving this goal, and we remain optimistic about our combination COVID-19 and influenza program, for which we are evaluating the next steps.”¹

“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,” Professor Ugur Sahin, MD, CEO, and cofounder of BioNTech added in the press release.¹

References

1. Pfizer and BioNTech Provide Update on mRNA-based Combination Vaccine Program Against Influenza and COVID-19 in Individuals 18-64 Years of Age. New release. Pfizer. August 16, 2024. Accessed August 16, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-mrna-based-combination
2. Pfizer and BioNTech received US FDA Fast Track Designation for single-dose mRNA-based vaccine candidate against COVID-19 and influenza. News release. Pfizer. December 9, 2022. Accessed October 31, 2023. https://www.pfizer.com/news/announcements/pfizer-and-biontech-receive-us-fda-fast-track-designation-single-dose-mrna-based
3. Massaro L. Pfizer BioNTech topline data show robust immune response for COVID-19/influenza vaccine combination. Patient Care. October 31, 2023. https://www.patientcareonline.com/view/pfizer-biontech-topline-data-show-robust-immune-response-for-covid-19-influenza-vaccine-combination