FDA says comparator dose scuppered Moderna's flu jab filing

The FDA has defended its decision to issue a refusal-to-file (RTF) letter for Moderna's new mRNA-based influenza vaccine, claiming the company had not used an appropriate control group in its pivotal trial.

The agency has said that Moderna should have used a higher dose of the comparator vaccine used as a control in its study of mRNA-101, as that would be the usual practice in some of the patients enrolled into the trial.

There had been speculation that the decision stemmed from a repeatedly stated objective by HHS Secretary Robert F Kennedy Jr to make all marketing applications use placebo control groups.

At a press briefing, however, FDA spokesperson Andrew Nixon said the agency wanted to see a higher dose of the comparator vaccine given to people aged 65 and older in the study, which enrolled a population aged 50 and above, saying that would be standard practice.

He claimed that Moderna "refused to follow very clear FDA guidance from 2024 to test its product in a clinical trial against a CDC-recommended flu vaccine to compare safety and efficacy," adding that the company "exposed participants, age 65 and over, to increased risk of severe illness by giving them a substandard of care against the recommendation of FDA career scientists."

The FDA has also insisted that Kennedy had played no part in the decision, according to a report in The Hill, and was thought to be unaware of the RTF until it was publicised. It also refused to comment on a STAT report that Vinay Prasad, the director of the FDA division responsible for handling vaccine reviews, had overruled senior staffers to issue the RTF.

Moderna – which has requested a meeting with the FDA to try to get the application back on track – reiterated its position that the FDA had "reviewed and cleared the trial design as adequate before the study began 18 months ago." Meanwhile, mRNA-1010 remains under regulatory review in the EU, Canada, and Australia.

In its main clinical trial, mRNA-1010 was shown to be 26.6% more effective than the comparator flu shot in adults aged 50 years and older. mRNA-based flu vaccines, which can be produced rapidly, have the potential advantage of more precisely matching circulating strains.

The FDA said at the briefing that Moderna may be able to submit the same data "if they come back [and] maybe even show some humility," and would also consider a refiled application for approval in a younger age cohort.

UK milestone

In other news this week, Moderna said it had won authorisation in the UK for its updated COVID-19 vaccine, a version of Spikevax targeting the SARS-CoV-2 LP.8.1 variant, which is the first commercially licensed mRNA vaccine to be manufactured in the UK and will be used to supply the NHS spring 2026 vaccination campaigns.