The US Food and Drug Administration (FDA) has refused to review Moderna’s seasonal influenza jab, mRNA-1010, as the shifting vaccine landscape within the country continues to prove volatile for pharma companies.
The FDA sent a refusal-to-file (RTF) notice to Moderna, which was signed by the Center for Biologics Evaluation and Research (CBER) director, Vinay Prasad.
In the letter, the CBER cites the lack of an “adequate and well-controlled” study within Moderna’s biologics license application (BLA) for mRNA-1010 – leading the agency to deem the vaccine unsuitable for review. Moderna’s investigational vaccine uses the same underlying mRNA technology as its marketed Covid-19 jab Spikevax, which the FDA approved in 2022. The modality works by instructing cells to produce specific proteins that can recognise and fight pathogens.
This decision primarily revolves around the FDA’s belief that the control arm used in the study “does not reflect the best-available standard of care” (SoC) within the US at the time of the Phase III trial (NCT05415462). As per ClinicalTrials.gov, Moderna opted to use GSK’s marketed quadrivalent jab, Fluarix Tetra as the comparator in its registrational study. Fluarix Tetra, also known as Fluarix Quadrivalent, is an FDA-approved influenza vaccine.
The FDA shun sent Moderna’s stock sliding 10.5% from $41.99 at market close on 10 February to $37.60 at opening on 11 February. Moderna has a market cap of $14.7bn.
Moderna rebuts FDA stance on mRNA-1010
In a 10 February statement addressing the RTF, Moderna refuted the FDA’s claims, noting: “Neither the relevant regulation, 21 C.F.R. § 314.126, covering adequate and well-controlled studies, nor the FDA’s guidance for industry on seasonal influenza vaccines contain any reference to the use of a comparator reflecting the best-available SoC”.
Moderna also stated that the letter is “inconsistent” with what the agency told the drugmaker in April 2024 and August 2025. The company claimed that the department did not issue any feedback on the Phase III trial’s adequacy at protocol submission or study initiation.
Moderna’s CEO Stéphane Bancel said: “It should not be controversial to conduct a comprehensive review of a flu vaccine submission that uses an FDA-approved vaccine as a comparator in a study that was discussed and agreed on with CBER prior to starting.”
The Massachusetts-based pharma has requested a Type A meeting with the FDA to review next steps for mRNA-1010.
Currently, there are no publicly available references to a specific SoC vaccine option for influenza prevention available either on the FDA or the Centers for Disease Control’s (CDC) websites. The FDA currently authorises the use of 26 influenza vaccines across different age ranges and viral strains.
Moderna feels effect of mRNA sidelining
In a research note reacting to Moderna’s application rejection, Citi analysts stated that the agency’s shift in approach is “not unexpected” within the evolving regulatory environment.
While Moderna has requested a Type A meeting with the FDA, the analysts note that maintaining a vaccine-focused business leaves the company “highly exposed to volatility.”
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mRNA-based vaccines have firmly been under the regulatory spotlight in the US under the Trump administration, leading to the deprioritisation of their development by US Health Secretary, Robert F Kennedy Junior (RFK Jr). This is largely due to concerns around their efficacy and safety.
The vaccines have been the subject of notable federal funding cuts – triggering a further knock-on impact on venture financing. Outside of the infectious disease area, cancer vaccine developers are also feeling the strain as the Trump administration looks to distance public health reliance away from mRNA technologies.
Within the FDA, CBER lead Vinay Prasad has also been a vocal critic of mRNA vaccines. Previously, he called the wider decision to deprioritise mRNA vaccine technology research “wise”, citing long-term safety and better alternatives.
William Blair analyst Myles Minter separately stated that the RTF marks a “substantial hit to the probability of success for mRNA-1010, and in turn mRNA-1083’s (combo flu/COVID vaccine) US approvability”.
In a LinkedIn post, Julien Willard, head of research & investments at royalty investment firm BioPalace, highlighted the increasing importance of addressing political risks in investment memos.
“The FDA letter to Moderna illustrates why every investment memo must explicitly address political risks, not only policy-related ones; especially when the underlying asset operates in politically sensitive domains such as sexual health and vaccines,” Willard stated.
Annabel Kartal-Allen is a reporter for Clinical Trials Arena, Pharmaceutical Technology and Medical Device Network based in London, UK. She frequently reports on the pharmaceutical and nutraceutical industries. Find Annabel on LinkedIn
A version of this article was originally posted at Pharmaceutical Technology and is reposted here. Any reposting should credit both the GLP and original article. Find Pharmaceutical Technology on X @PharmaTechFocus
