Makary Cites 'Zero Benefit' for Seniors, Signals Tougher Scrutiny on Next-Gen Shots Amid Ongoing Safety Debates

December 3, 2025 | Washington, D.C. – Reporting based on FDA Commissioner Marty Makary's exclusive interview on Fox News, November 29, 2025, and subsequent agency statements.

In a stark assessment that has sent ripples through the pharmaceutical industry and public health circles, FDA Commissioner Marty Makary announced that Pfizer's experimental mRNA-based influenza vaccine has "failed" in its clinical trial among seniors, the very demographic it was designed to protect most urgently. Speaking on Fox News last Friday, Makary described the trial results as showing "zero benefit," raising fresh questions about the viability of mRNA technology beyond its COVID-19 applications and prompting calls for more rigorous data before any potential approval.

The vaccine, known internally as PF-07941309, represents Pfizer's ambitious push into next-generation flu shots using the same messenger RNA platform that powered its blockbuster COVID-19 vaccine, Comirnaty. However, the Phase 3 trial data, which enrolled over 25,000 participants including a significant cohort of adults aged 65 and older, fell short of efficacy benchmarks for this high-risk group. Makary emphasized that while the shot met some overall endpoints, its performance in seniors—the population hit hardest by seasonal flu—was underwhelming, with no statistically significant reduction in flu-related illnesses or hospitalizations compared to placebo.

"This mRNA flu vaccine failed in seniors," Makary stated bluntly during the interview. "The trial showed zero benefit. We need new data that proves it actually works for those who need it most before we even consider greenlighting it." His comments come at a time when the FDA is already overhauling its vaccine approval processes in response to post-market surveillance of COVID-19 shots, including revelations of rare but serious adverse events like myocarditis in young males.

The announcement has drawn sharp reactions. Pfizer, in a statement released Monday, acknowledged the trial's mixed outcomes but defended the technology's promise, noting that "additional analyses are underway" and that the vaccine demonstrated "robust immune responses" in younger adults. "We're committed to addressing the FDA's concerns and exploring ways to enhance efficacy in older populations," a company spokesperson said. Shares of Pfizer dipped nearly 2% in pre-market trading following Makary's remarks, while competitors like Moderna, which is developing its own mRNA flu candidate, saw a slight uptick amid speculation of shifting market dynamics.

Public health experts are divided. Dr. Paul Offit, a vaccine developer and FDA advisory committee member, called the results "disappointing but not surprising," pointing to the inherent challenges of targeting the flu virus's rapid mutations with mRNA platforms. "mRNA shone in COVID because it was a stable target; flu is a shape-shifter," Offit said in an email to reporters. On the other hand, critics of accelerated vaccine approvals, including voices from the anti-mandate movement, hailed Makary's candor as a long-overdue pivot toward transparency. This group has long argued that mRNA vaccines were rushed to market during the pandemic, citing internal FDA memos that recently linked at least 10 pediatric deaths to COVID shots between 2021 and 2024.

Makary's tenure as commissioner, which began earlier this year under the incoming administration, has been marked by a tougher stance on biologics oversight. Just last week, the FDA's Center for Biologics Evaluation and Research (CBER), led by Dr. Vinay Prasad, issued a memo proposing stricter evidence requirements for all new vaccines, including demands for long-term safety data and subgroup analyses like those for seniors. Prasad's directive followed an internal review that flagged gaps in prior mRNA approvals, fueling broader debates about balancing innovation speed with risk mitigation.

The flu vaccine setback isn't isolated. Moderna's mRNA flu candidate, mRNA-1010, also faced hurdles in late-stage trials earlier this year, though it secured emergency use authorization in Europe for certain age groups. Globally, seasonal influenza claims up to 650,000 lives annually, with seniors accounting for the majority, making effective shots a public health imperative. The World Health Organization has urged manufacturers to prioritize elderly efficacy, warning that current traditional flu vaccines offer only 40-60% protection in this group.

As winter approaches and flu season looms, Makary's words underscore a pivotal moment for mRNA's flu ambitions. "We're not approving anything that doesn't deliver real-world value," he affirmed. For now, Pfizer must regroup with fresh trials or formulation tweaks, but the episode serves as a cautionary tale: the pandemic-era halo around mRNA may be fading, replaced by a demand for unassailable proof. Health officials, meanwhile, continue to recommend existing flu vaccines, emphasizing that even partial protection saves lives.