An mRNA flu jab candidate that was criticised and dismissed by US Health Sectretary Robert F Kennedy Jr has been unanimously endorsed by a Food and Drug Administration advisory panel, reports MedPage Today.
In two 9-0 votes, the Vaccines and Related Biological Products Advisory Committee said the benefits of Moderna’s trivalent flu vaccine far outweigh its risks for preventing flu in adults aged 50 to 64 – and in those who were even older.
“The data presented support that the benefits in both age groups outweighed the risks,” said Flor Munoz-Rivas, MD, of Baylor College of Medicine in Houston.
Moderna's vaccine is based on the mRNA platform it used to develop its lifesaving Covid shots, but under the leadership of Kennedy, HHS cancelled $500m in funding for mRNA vaccine research in favour of what he called “safer platforms”.
But panellists pointed to discrete benefits of mRNA vaccines.
“Having this technology available puts us in a position to be better prepared for emerging strains or pandemic strains in the future,” said Munoz-Rivas.
Hayley Gans, MD, of Stanford Medicine Children’s Health in California, highlighted the potential for lasting immune benefits beyond a single flu season.
“My biggest excitement about this particular vaccine is that it actually induces better T-cell responses,” she said. “We’ve been struggling with the current flu vaccines because they don’t maintain great immunity.”
The supporting data did have limitations, noted panellist Adam Berger, PhD, of the National Institutes of Health’s Office of the Director, including the pivotal study’s single-season length, limited efficacy data against influenza B, and the little data with the vaccine in immunocompromised or frail patients.
But he said the immunogenicity data presented were “very suggestive of potential efficacy clinically”, and noted the vaccine’s high efficacy compared with existing shots and the relatively reassuring safety data.
In the pivotal phase 3 Fluent randomised trial, the mRNA vaccine – which targeted influenza A/H1N1, A/H3N2, and B/Victoria – outperformed standard-dose flu shots, with a relative vaccine efficacy of 26.6% among all participants 50 and up and 27.4% for the 65-and-older subset.
People older than 65 accounted for most of the 2024-2025 season’s hospitalisations and deaths, according to CDC estimates, with 57.4% of all flu hospitalisations and 70.6% of all flu deaths happening in that age cohort.
After its dust-up with the FDA, Moderna is pursuing a traditional approval in adults aged 50 to 64 and an accelerated approval for those 65 and older, with a post-marketing effectiveness study planned in that older group that will cover two flu seasons.
In February, the agency initially rejected Moderna’s application, with then-vaccine chief Vinay Prasad, MD, MPH, asserting the company lacked an “adequate and well-controlled trial” as it failed to compare the mRNA vaccine with “the best-available standard of care in the United States at the time of the study”, a reference to the fact that the CDC recommends a high-dose vaccine for people 65 or older rather than the standard-dose shots used in the control arm.
The agency reversed after the drugmaker showed immune response data in the older subset at least matched the high-dose vaccines and committed to conducting a large and expensive randomised post-marketing study to compare effectiveness.
“The planned post-approval study will be important to answer some of the issues pertaining to efficacy and immunogenicity,” said panellist Hana El Sahly, MD, also of Baylor College of Medicine.
Reactogenicity messaging will need work
While serious adverse event (AE) data with the mRNA vaccine were “reassuring”, the greater rates of transient local (67.5% vs 32.1%) and systemic (58.0% vs 32.4%) AEs compared with the standard flu vaccines could be an issue for patients, according to El Sahly.
“While this is not a safety concern, this is an important acceptability concern, especially in light of vaccine alternatives,” El Sahly said. “Such reactions have to be highlighted in our approach if we are to increase the vaccination coverage in our populations.”
Having even a small percentage of people not going to work for one or two days because of AEs “is not trivial when we’re talking about millions of individuals”, she noted.
Retooling shots in mismatch years?
All of the current FDA-licensed flu vaccines are manufactured using egg-based, cell-culture based, or recombinant production technologies. Those production processes can take six to eight months to deliver vaccines after strain selection, a timeline that can slow reformulation during vaccine-strain mismatch seasons.
In addition, most of the vaccines use egg-based manufacturing, which can lead to egg-adaptive mutations.
Adding mRNA technology to the manufacturing line-up could avoid adaptive mutations and improve response when vaccines don’t match circulating flu strains. Moderna staff pointed to a two- to three-month turnaround from strain selection to production with its mRNA vaccines for Covid-19.
While the FDA is not required to follow the advice of its advisory committees in its approval decisions, it typically does.
See more from MedicalBrief archives:
Kennedy cancels $500m mRNA vaccine contracts
Moderna gets millions for mRNA jab against future pandemics