Pfizer Inc. and BioNTech SE  announced top-line results from their Phase 3 clinical trial to evaluate the companies’ combined mRNA vaccine candidate against influenza and COVID-19 in healthy individuals 18-64 years of age. The combination candidate consists of Pfizer’s mRNA-based influenza vaccine candidate with the companies’ licensed COVID-19 vaccine. The Phase 3 trial measured two primary immunogenicity objectives (immunogenicity against SARS-CoV-2 as well as immunogenicity against influenza A and B), of which one was met. In a separate Phase 2 trial, Pfizer evaluated trivalent (“tIRV”) influenza mRNA standalone vaccine candidates which demonstrated robust immunogenicity in individuals 18-64 years of age. The companies are evaluating adjustments to the combination vaccine candidate aimed at improving immune responses against influenza B and will discuss next steps with health authorities.

Update on Phase 3 Pfizer and BioNTech Combination Vaccine Trial

The Phase 3 randomized, observer-blinded study (NCT06178991) enrolled more than 8,000 adults 18 through 64 years of age to evaluate the safety, tolerability, and immunogenicity of a single dose combination vaccine candidate against influenza and COVID-19. In this clinical trial, the vaccine candidate was compared to a licensed influenza vaccine and the companies’ licensed COVID-19 vaccine given at the same visit. The primary immunogenicity objectives were to demonstrate that the antibody responses to influenza (hemagglutination inhibition, “HAI”) and to SARS-CoV-2 (neutralizing titer, “NT”) elicited by the combination vaccine candidate were non-inferior (“NI”) to standard of care (“SOC”). Compared to a licensed influenza vaccine, the tIRV 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 (“GMT”) and seroconversion against the influenza B strain. In addition, the formulation demonstrated comparable responses against SARS-CoV-2 versus the companies’ licensed COVID-19 vaccine. No safety signals with the combination vaccine have been identified in an ongoing safety data review. Participants who received a licensed influenza and COVID-19 vaccine with co-administration continued to elicit robust immune responses against both influenza and COVID-19 with no safety signals identified to date.

“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,” said Annaliesa Anderson, PhD, Senior Vice President and Head, Vaccine Research and Development at Pfizer. “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.”

“We are dedicated to developing combination vaccines which provide broader protection against multiple respiratory diseases,” said Prof. Ugur Sahin, M.D., CEO and Co-founder of BioNTech. “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. 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.”

Update on Pfizer's Phase 2 Second Generation Influenza Vaccine Trial

Pfizer’s Phase 2 trial (NCT06436703) to evaluate second-generation candidates against influenza was initiated earlier this year and enrolled 450 participants 18-64 years of age, who were randomized to receive investigational mRNA-based influenza vaccines or influenza vaccines approved by the U.S. Food and Drug Administration (“FDA”). As previously stated, Pfizer announced positive top-line Phase 3 results from its first-generation quadrivalent (“qIRV”) vaccine candidate which achieved the first and only demonstration of efficacy for an mRNA vaccine in a group of study participants 18-64 years of age. The primary endpoints for this qIRV first-generation candidate were not met in adults aged 65 and older, as statistical non-inferior relative vaccine efficacy (“rVE”) compared to a licensed influenza vaccine was not met based on the number of cases accrued. Pfizer developed second-generation candidates with the goal of improving immunogenicity and potentially breadth of protection, including new tIRV formulations that matched updated recommendations by the World Health Organization (“WHO”) and the FDA’s Vaccines and Related Biological Products Advisory Committee (“VRBPAC”). The tIRV formulations elicited robust influenza A responses and B responses, including continued trend of higher influenza A responses versus a licensed influenza vaccine. There were no safety signals reported. Data from this Phase 2 trial for adults 65 years of age and older will become available at a later date.

Pfizer will also continue to evaluate its influenza vaccine program and discuss next steps with health authorities.