Pfizer's mRNA flu vaccine hits primary goals in phase 3 trial, but secondary miss raises questions

Pfizer has capped off a landmark six weeks for the push to apply mRNA to influenza. Following a flurry of positive updates from Pfizer and chief mRNA rival Moderna, the Big Pharma has revealed a phase 3 trial of its mRNA flu candidate met both primary endpoints—but a secondary endpoint miss raises questions.

The concept of using mRNA to protect against flu was on somewhat shaky ground as the summer drew to a close. Then, Moderna revealed a phase 3 win for its mRNA influenza candidate. Within weeks, Pfizer and Moderna shared upbeat updates from phase 1/2 trials of their rival combination COVID-19-influenza vaccine candidates, setting the stage for pivotal trials and another race to market.

Pfizer kept the good news coming Tuesday when it used its third-quarter financial results (PDF) to share top-line data from a phase 3 trial of its mRNA influenza candidate. The ongoing phase 3 clinical trial met both primary endpoints in the 18- to 64-year-old cohort. 

The primary efficacy endpoint compared the proportion of participants who had lab-confirmed influenza and associated symptoms after receiving either Pfizer’s investigational shot or a licensed quadrivalent influenza vaccine. Pfizer found its “candidate demonstrated non-inferiority and superiority to a licensed flu vaccine at the time of the primary analysis.” 

Efficacy persisted through the end-of-season analysis, with Pfizer’s challenger remaining noninferior to the licensed vaccine. The primary and end-of-season analyses clumped influenza A and B cases together, but most cases in the cohort were influenza A infections. The fact the data set skews toward influenza A leaves scope to question the efficacy of the mRNA candidate against influenza B.

A secondary endpoint provides support for the questioning. The trial met its secondary immunogenicity endpoints for A strains but missed for B strains. The full results may help show whether influenza B is a chink in the armor of the candidate, but Pfizer is yet to share any figures. The only other detail revealed to date is that the safety profile was comparable to that of a standard flu vaccine. 

Details will matter, because Pfizer is entering a competitive space. Flu vaccine incumbents such as Sanofi will fight to hold on to the market, and Pfizer could be up against Moderna’s rival mRNA vaccine, which showed higher antibody levels than GSK's Fluarix for all four influenza strains, two each for influenza A and B, in a phase 3 trial. 

But, similarly to Pfizer, Moderna missed on the B strains initially. After tweaking the formula, the candidate hit on all endpoints and got a clean phase 3 win. The World Health Organization recommends protection against two A subtypes, H1N1 and H3N2, as well as two influenza B strains, Victoria and Yamagata, be included in annual flu shots.

The Big Pharma is yet to show how its vaccine performs in people aged 65 years and older, a key part of the flu shot market. Pfizer expects to share data from its phase 3 cohort of older adults later this year.