Influenza Vaccine, mRNA(Moderna)

Moderna, reeling under a recent late-stage setback to its norovirus vaccine programme, finally has some good news to celebrate. After a winding regulatory battle, the FDA authorised the company's influenza vaccine mFlusiva (mRNA-1010) for use in all adults aged 50 years and older. The product is slated to hit the shelves in the coming weeks, ahead of the 2026–2027 respiratory virus season."Our fourth approved product in the US and the first mRNA-based flu vaccine, demonstrates the continued strength and versatility of our mRNA platform," said CEO Stéphane Bancel. "Flu remains a significant public health challenge, and mFlusiva provides an important new option for America's seniors."mFlusiva now joins Moderna's diverse respiratory vaccine portfolio, which includes COVID-19 shots Spikevax and mNexspike, and RSV vaccine mResvia.The traditional approval of mFlusiva for adults aged 50 through 64 years was supported by a global Phase III trial of over 40,000 participants, wherein mFlusiva achieved a relative vaccine efficacy against influenza illness of 26.6% versus GSK's Fluarix, the standard-dose active comparator.Meanwhile, the mRNA flu vaccine secured accelerated approval in adults aged 65 and older based on a separate trial enrolling 2,992 US adults in this age bracket, pitting it against a high-dose inactivated influenza vaccine comparator. Confirmation of clinical benefit in this population will be evaluated through a 400,000-participant post-marketing study in this cohort.Story so far..mFlusiva's regulatory journey was anything but straightforward. In February this year, the FDA's Center for Biologics Evaluation and Research (CBER) issued a refusal-to-file letter, declining to review the marketing application for the vaccine despite Moderna's use of a priority review voucher. The letter, signed by then-CBER director Vinay Prasad, raised no safety or efficacy concerns but objected to the company's use of a licensed seasonal flu vaccine as its Phase III comparator. While Moderna dubbed the decision "inconsistent" with earlier feedback, the FDA's then-commissioner Marty Makary countered that the company had ignored "very clear" agency guidance.The stand-off, however, was short-lived. Another meeting shortly followed — reportedly under pressure from the White House — and the regulator agreed to accept the application, setting a target action date of August 5. Amid this, Prasad announced he would step down from CBER for a second time following a string of contentious decisions on vaccines and gene therapies.An FDA advisory committee (adcom) meeting was scheduled for June 18, and briefing documents released ahead found no major deficiencies with mFlusiva's application, sending Moderna's shares up more than 6% at the time. The agency staff, however, did flag evidence gaps in immunocompromised and frail older populations, and noted that pivotal trial data covered only a single flu season. At the adcom, panel members voted 9-0 in favour of mFlusiva, praising the vaccine's immunogenicity data and its potential to elicit stronger T-cell responses than existing flu shots, while urging the company to ensure its large post-marketing trial addresses remaining uncertainties in high-risk populations.Regulatory submissions for the Moderna vaccine also remain under review in the EU, Canada and Australia, with additional filings planned during the year.mRNA under fireThe Department of Health and Human Services has repeatedly raised unsubstantiated safety concerns regarding mRNA vaccines, and last August cancelled about $500 million in funding for 22 mRNA vaccine programmes.The increased scrutiny of mRNA vaccines prompted Moderna to withdraw its FDA application for influenza/COVID-19 combination vaccine mRNA-1083 last year after regulators sought additional Phase III flu efficacy data. The filing had been intended to follow the review of mFlusiva.Meanwhile, Pfizer too is developing a standalone mRNA influenza vaccine — which showed favourable Phase III efficacy data — in addition to an influenza/COVID-19 combination vaccine in collaboration with BioNTech.

Despite a major curveball thrown by the FDA earlier this year, Moderna has managed to strike true with a U.S. approval for its mRNA-based influenza vaccine. The FDA on late Wednesday signed off on Moderna’s vaccine, christened mFlusiva, to prevent seasonal influenza in all adults ages 50 years and older. With the green light, Moderna has scooped up its fourth FDA nod and cleared the way for the first-ever flu shot leveraging mRNA technology in the United States. The vaccine’s odds of approval stateside were thrown into flux in February when the FDA issued Moderna a rare refusal to file (RTF) letter, citing concerns with the design of the phase 3 trial for the shot, at the time known as mRNA-1010. Moderna publicly pushed back against the FDA’s decision not to take up its application, and the agency—whose Center for Biologics Evaluation and Research (CBER) responsible for vaccines was at the time headed up by controversial director Vinay Prasad, M.D.—reversed course a little over a week later. The FDA’s concerns specifically came down to the use of a standard-dose flu vaccine as the comparator arm in one of the trial’s supporting mFlusiva’s approval. The FDA at the time suggested that it had issues because Moderna had not used “the best-available standard of care” in its study—a position the company disagreed with and noted that the FDA had not flagged as a problem when previously discussing trial protocols. At one additional checkpoint on the way to approval, the FDA’s Vaccines and Related Biological Products Advisory Committee voted unanimously that mFlusiva’s benefits outweighed its risks across both the 50-to-64-year age group and in patients ages 65 years and older. With regards to those age groups, mFlusiva has secured a traditional FDA approval in the 50-to-64-year bracket and an accelerated nod in the older group. The decision was backed up by data from a pair of phase 3 trials, with the study in the younger patient group comparing mFlusiva’s relative vaccine efficacy, among other measures, against a standard-dose comparator shot. The study in adults ages 65 and up pitted mFlusiva against a high-dose inactivated flu shot but with immunogenicity as the primary objective. As required by an accelerated approval, Moderna noted that it will run a postmarketing trial to confirm its vaccine’s benefit in the older patient population. With the colder months drawing nearer, Moderna says it expects to make mFlusiva available in the U.S. for the 2026-2027 respiratory virus season. The new vaccine will join the stable of Moderna’s other mRNA vaccines Spikevax and mNexspike for COVID-19, and mResvia in respiratory syncytial virus. "The FDA approval of mFlusiva, our fourth approved product in the United States and the first mRNA-based flu vaccine, demonstrates the continued strength and versatility of our mRNA platform," Moderna helmsman Stéphane Bancel said in a Wednesday statement. "Flu remains a significant public health challenge, and mFlusiva provides an important new option for America's seniors,” he continued. “This approval also reflects the ongoing potential of our mRNA platform to help address important public health challenges through continued scientific innovation.” Outside the U.S., Moderna’s mFlusiva application has been taken under review in the European Union, Canada and Australia. While the solo flu shot is awaiting a verdict in Europe, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended approval for Moderna’s mCombriax in patients ages 50 and up. That mRNA vaccine is designed to confer protection against COVID and flu in a single combo shot.