FDA Declines to Review Moderna's Application for New Flu Vaccine
In a significant regulatory decision, the US Food and Drug Administration (FDA) has declined to review Moderna's application to license a new messenger RNA (mRNA) flu vaccine. This unexpected move comes despite the FDA previously giving preliminary approval to the project, and could establish important precedents for all new and updated vaccines in the United States.
Regulatory Concerns Over Trial Design
The FDA's refusal centres on concerns about the design of Moderna's clinical trials. According to a letter signed by Vinay Prasad, director of the Center for Biologics Evaluation and Research (CBER), the agency will not review evidence from Moderna's trials because they compared the new mRNA shot to existing standard flu vaccines rather than to shots specifically designed for high-risk individuals.
Prasad stated that the FDA does not consider the Moderna trial to be "adequate and well-controlled" because comparing the new vaccine to standard flu shots "does not reflect the best-available standard of care." The FDA issued a refusal-to-file letter, indicating it will not consider the licensing application until Moderna provides additional information, though the specific requirements remain unspecified.
Moderna's Response and Clinical Evidence
Moderna's chief executive, Stéphane Bancel, responded to the decision by emphasising that the refusal "did not identify any safety or efficacy concerns" with the experimental vaccine. Bancel argued that "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 company has requested a meeting with FDA officials to discuss the refusal. Moderna's research showed promising results, with their new vaccine eliciting better antibody responses than existing vaccines in adult populations. Their study involved:
- Comparing the new mRNA vaccine against existing high-dose flu vaccines in adults aged 65 and older
- Comparing the new shot to standard flu vaccines in adults under 65
- Finding no safety concerns in either population group
Another Moderna trial comparing the new vaccine against standard flu shots in adults aged 50 and older has completed but not yet published results.
Broader Implications for Vaccine Development
This decision represents the latest development in what appears to be changing approaches to vaccine regulation under the current administration. In January, officials decided to stop fully recommending one-third of routine childhood vaccines, including flu vaccines, moving them to "shared clinical decision-making" status without consulting outside vaccine advisers or medical providers.
The potential implications extend beyond this specific application. mRNA vaccines have demonstrated significant advantages over traditional egg-based vaccines, including:
- Potentially greater effectiveness against certain illnesses
- Faster updating capabilities to match evolving flu strains
- Improved responsiveness to pandemic threats
While there have been no public changes to rules governing clinical trials for vaccines, a leaked internal email from November suggested the FDA would "revise the annual flu vaccine framework," including tests measuring vaccine effectiveness.
International Context and Future Prospects
Despite the setback in the United States, Moderna's licensing application continues to progress internationally. Regulatory reviews are currently underway in the European Union, Canada, and Australia, suggesting different regulatory approaches to innovative vaccine technologies across global markets.
The US Department of Health and Human Services has not responded to questions about whether FDA rules have changed or if this decision represents a broader policy shift toward approving flu vaccines only for high-risk populations rather than the general public.
This development highlights ongoing tensions between pharmaceutical innovation and regulatory standards, particularly concerning novel vaccine technologies that could transform public health responses to seasonal illnesses and potential pandemics.
