Pfizer and BioNTech announced top-line results from their Phase 3 clinical trial evaluating their combined mRNA vaccine candidate against influenza and COVID-19 in healthy individuals aged 18-64. The trial (NCT06178991) assessed the safety, tolerability, and immunogenicity of a single dose of the combination vaccine compared to a licensed influenza vaccine and the companies’ licensed COVID-19 vaccine given at the same visit.
The combination vaccine consists of Pfizer’s mRNA-based influenza vaccine candidate combined with the companies’ licensed COVID-19 vaccine. The Phase 3 trial measured two primary immunogenicity objectives: immunogenicity against SARS-CoV-2 and immunogenicity against influenza A and B. One of these objectives was met.
Immunogenicity Results
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 the standard of care (SOC). The tIRV formulation elicited robust influenza A responses, showing 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. The formulation demonstrated comparable responses against SARS-CoV-2 versus the companies’ licensed COVID-19 vaccine. No safety signals were identified in an ongoing safety data review.
Annaliesa Anderson, PhD, Senior Vice President and Head, Vaccine Research and Development at Pfizer, stated, "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."
Phase 2 Influenza Vaccine Trial
Pfizer’s Phase 2 trial (NCT06436703) evaluated second-generation candidates against influenza, enrolling 450 participants aged 18-64. Participants were randomized to receive investigational mRNA-based influenza vaccines or FDA-approved influenza vaccines. The tIRV formulations elicited robust influenza A and B responses, including a continued trend of higher influenza A responses versus a licensed influenza vaccine. No safety signals were reported. Data from this Phase 2 trial for adults 65 years of age and older will be available later.
Future Directions
Pfizer and BioNTech are evaluating adjustments to the combination vaccine candidate aimed at improving immune responses against influenza B and will discuss next steps with health authorities. The companies remain committed to developing combination vaccines that provide broader protection against multiple respiratory diseases.
Prof. Ugur Sahin, M.D., CEO and Co-founder of BioNTech, commented, “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.”
Influenza Burden
Influenza causes an estimated 140,000 to 710,000 hospitalizations and 12,000 to 52,000 deaths in the U.S. each year, resulting in about $25 billion in economic loss. Current influenza vaccines typically confer 40% to 60% protection each year, with even lower protection in years with poor matching of strains. The flexibility of mRNA technology could potentially allow better strain matches in future years and enable rapid, large-scale manufacturing of vaccines in a pandemic influenza situation.
