Pfizer’s Experimental mRNA Flu Vaccine Demonstrates Superior Efficacy in Phase III Trial

NEW YORK, NY – November 20, 2025 — Findings from a pivotal Phase III study, published Wednesday in the New England Journal of Medicine (NEJM), demonstrated that Pfizer’s experimental mRNA-based influenza vaccine was superior to Sanofi’s market-leading inactivated flu shot, Fluzone, in preventing illness.

The randomized trial involved over 18,000 adults aged 18 to 64 from the US, South Africa, and the Philippines, who received one of the two quadrivalent vaccines during the 2022–2023 influenza season.

Superior Efficacy and Relative Reduction in Illness

Pfizer’s mRNA jab met the study’s primary endpoint, demonstrating superiority over Fluzone in relative efficacy, measured by the reduction in participants with laboratory-confirmed infection associated with flu-like illness at least 14 days post-vaccination.

• Case Count: Only 57 cases of flu-like illness were reported in the experimental mRNA arm, compared to 87 cases in the Fluzone recipient arm.
• Relative Efficacy: This yielded a relative efficacy of 34.5% for the mRNA shot.
• Overall Efficacy Estimate: An end-of-season analysis showed a relative vaccine efficacy of 28.7%. Pfizer estimated this suggests the mRNA vaccine had an overall efficacy between 60% to 67%, relative to the estimated 44% to 54% efficacy of FDA-approved vaccines that season.

Pfizer concluded that its mRNA vaccine provided “both similar and improved prevention of a first episode of laboratory-confirmed influenza” in the trial’s patient population.

Safety Profile and Regulatory Uncertainties

Both the experimental mRNA jab and Fluzone shared similar adverse event profiles. However, reactogenicity events (e.g., pain at the injection site, fever) occurred more frequently with the mRNA vaccine:

• Overall Local Reactions: 70.1% for mRNA vs. 43.1% for Fluzone.
• Overall Systemic Events: 65.8% for mRNA vs. 48.7% for Fluzone.

Pfizer noted that most events were mild or moderate and transient, with no clinically meaningful differences in severe events between the groups.

Despite the clinical success, the vaccine’s regulatory pathway faces challenges due to persistent doubt cast by some U.S. health leaders regarding mRNA-based vaccines. This uncertainty was recently highlighted by the cancellation of approximately $500 million in government funding for 22 mRNA vaccine programs.

Separately, Pfizer’s mRNA competitor, Moderna, withdrew its mRNA COVID-19/flu combination jab application in May. A separate Phase III study of Moderna’s standalone mRNA flu vaccine in adults aged 50 and older showed a relative vaccine efficacy of 26.6% versus a standard-dose flu shot.