FDA Advisory Committee Unanimous Approval and Regulatory Challenges

Moderna's (MRNA) mRNA-based influenza vaccine, mFluSiva (developmental name mRNA-1010), received a unanimous 9-0 recommendation for approval from the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC). Both the standard approval for adults aged 50-64 and the accelerated approval for those aged 65 and older received full support. Notably, in February 2026, Vinay Prasad, the FDA's head of vaccine division, issued a refusal-to-file letter, stating that the comparator did not reflect 'the best standard of care.' However, just one week later, this decision was reversed, and the review was accepted, marking an unusual regulatory development.

Phase 3 NEJM Published Clinical Data

The P304 pivotal trial enrolled 40,805 participants (aged 50 and older) across 11 countries and achieved a relative vaccine efficacy (rVE) of 26.6% (95% CI 16.7-35.4%) compared to the existing standard-dose influenza vaccine, as published in the New England Journal of Medicine. Strain-specific rVEs were 29.6% for A/H1N1, 22.2% for A/H3N2, and 29.1% for B/Victoria. In the 65-year-old and older subgroup, the rVE was 27.4%, demonstrating consistent efficacy across all age groups. In terms of safety, injection site pain was reported in 65.8% of cases (compared to 29.8% in the control group), but most were mild to moderate and transient. No cases of myocarditis or pericarditis were reported. A total of 968 confirmed influenza cases were recorded, exceeding the target of 836.

First mRNA Challenge in an Oligopolistic Market

The global influenza vaccine market is expected to reach approximately $9.96 billion (USD) in 2026, with Sanofi (SNY) (Fluzone High-Dose and Flublok), CSL Seqirus (FLUAD and Flucelvax), and GSK (GSK) controlling over 60% of the market share. mFluSiva is the first mRNA-based seasonal influenza vaccine, aiming to differentiate itself through its speed of variant response and production flexibility. Sanofi's Fluzone High-Dose has demonstrated an rVE of 24.2% in the 65-year-old and older market compared to the standard vaccine, and mFluSiva's rVE of 27.4% (65+) falls within a comparable range. Moderna has already secured approval in the EU for its COVID-influenza combination vaccine, mCombriax (for those aged 50 and older), and aims to capture a significant share of the European respiratory vaccine market, which is valued at $1.8 to $2 billion.

PDUFA Schedule and Remaining Challenges

The FDA's PDUFA target action date is August 5, 2026, and approval would allow for supply during the 2026-2027 influenza season. The accelerated approval for those aged 65 and older requires a confirmatory study involving up to 800,000 participants over two influenza seasons. Remaining challenges include the lack of direct comparative data with high-dose vaccines (Fluzone HD and FLUAD), insufficient data on immunocompromised patients and frail elderly individuals, limitations of single-season data, and the absence of data on co-administration with other respiratory vaccines.