BioNTech SE (Nasdaq: BNTX) today revealed top-line results from their Phase 3 clinical trial evaluating a combined mRNA vaccine candidate against influenza and COVID-19 in healthy adults aged 18-64. This combination vaccine includes Pfizer’s mRNA-based influenza candidate and the companies’ authorized COVID-19 vaccine. The trial assessed two primary immunogenicity objectives—response against SARS-CoV-2 and influenza A and B—meeting one of these objectives. Meanwhile, a separate Phase 2 trial showed strong immunogenicity in a standalone trivalent influenza mRNA vaccine candidate among adults aged 18-64. The companies are now considering modifications to enhance immune responses against influenza B in the combination vaccine and will consult with health authorities on next steps.
Phase 3 Pfizer and BioNTech Combination Vaccine Trial Overview
The Phase 3 randomized, observer-blinded study (NCT06178991) involved over 8,000 adults aged 18-64, assessing the safety, tolerability, and immunogenicity of a single-dose combination vaccine for influenza and COVID-19. The trial compared the combination vaccine to a licensed influenza vaccine and the companies’ COVID-19 vaccine administered during the same visit. The primary objectives focused on demonstrating that the antibody responses to influenza (hemagglutination inhibition, “HAI”) and SARS-CoV-2 (neutralizing titer, “NT”) induced by the combination vaccine were non-inferior (“NI”) to standard of care (“SOC”). The tIRV formulation notably elicited robust responses against influenza A, showing a continued trend of higher responses compared to a licensed influenza vaccine, though it showed lower geometric mean titers (“GMT”) and seroconversion against the influenza B strain. The combination vaccine also produced comparable responses against SARS-CoV-2, similar to the companies’ licensed COVID-19 vaccine. No safety concerns were identified in the ongoing review of safety data, and participants receiving the licensed influenza and COVID-19 vaccines concurrently maintained strong immune responses to both viruses without any safety issues to date.
“We are encouraged by the strong immunogenicity observed with our combination vaccine against influenza A, similar to our initial quadrivalent influenza vaccine where we saw superior relative vaccine efficacy compared to a flu vaccine comparator,” said Annaliesa Anderson, PhD, Senior Vice President and Head of Vaccine Research and Development at Pfizer. “We are committed to developing vaccines that reduce the burden of respiratory diseases, and we believe combination vaccines are the most efficient way to achieve this. Today’s results offer valuable insights as we work towards this goal, and we remain optimistic about our combination COVID-19 and influenza program as we evaluate the next steps.”
Prof. Ugur Sahin, M.D., CEO and Co-founder of BioNTech, added, “We are dedicated to developing combination vaccines that provide broader protection against multiple respiratory diseases. The insights from this trial are crucial in guiding the further development of Pfizer’s and our combination vaccine program against influenza and COVID-19. We are committed to leveraging our experience in developing mRNA-based vaccine candidates against multiple antigens, and we believe we can achieve this in collaboration with our partner Pfizer.”
Update on Pfizer’s Phase 2 Second-Generation Influenza Vaccine Trial
Pfizer’s Phase 2 trial (NCT06436703) began earlier this year to evaluate second-generation influenza vaccine candidates, enrolling 450 participants aged 18-64. Participants were randomized to receive either investigational mRNA-based influenza vaccines or FDA-approved influenza vaccines. Previously, Pfizer announced positive Phase 3 results from its first-generation quadrivalent (“qIRV”) vaccine candidate, the first and only mRNA vaccine to demonstrate efficacy in study participants aged 18-64. The primary endpoints for this qIRV candidate were not met in adults aged 65 and older, as statistical non-inferiority in relative vaccine efficacy (“rVE”) compared to a licensed influenza vaccine was not achieved. In response, Pfizer developed second-generation candidates to improve immunogenicity and potentially broaden protection, including new tIRV formulations aligned with updated recommendations from the World Health Organization (“WHO”) and the FDA’s Vaccines and Related Biological Products Advisory Committee (“VRBPAC”). The tIRV formulations produced strong responses against influenza A and B, including a continued trend of higher responses to influenza A compared to a licensed influenza vaccine. No safety concerns were reported. Data from this Phase 2 trial for participants aged 65 and older will be available at a later date.
Pfizer will continue evaluating its influenza vaccine program and discussing next steps with health authorities.
About Influenza
Influenza leads to an estimated 140,000 to 710,000 hospitalizations and 12,000 to 52,000 deaths annually in the U.S., with about $25 billion in economic losses each year. Individuals aged 65 and older face a higher risk of serious complications from influenza, including hospitalization and death. Even with well-matched vaccines, current influenza vaccines typically provide 40% to 60% protection each year, with even lower protection in years with poor strain matching. Influenza has a disproportionate impact on racial and ethnic minority groups in the U.S. Black Americans are nearly twice as likely as white counterparts to be hospitalized for influenza, while Latino and Indigenous Americans are 1.2 and 1.3 times more likely, respectively.
Given the constantly changing nature of influenza strains, predicting the best match for the next season’s vaccine is challenging for global health experts, as those strains are selected over six months before the flu season begins. The flexibility of mRNA technology and its rapid manufacturing capabilities could potentially lead to better strain matches in future years. In a pandemic influenza situation, mRNA technology could also enable rapid, large-scale vaccine production.
