Moderna Flu Vaccine Rejected by FDA Despite Positive Trial Data
- The Food and Drug Administration (FDA) has declined to review Moderna’s application for its investigational influenza vaccine, mRNA-1010, issuing a “refusal-to-file” (RTF) letter on February 10, 2026.
- According to Moderna, the FDA’s decision does not stem from concerns about the safety or efficacy of the mRNA-1010 vaccine.
- This determination is particularly noteworthy as the FDA did not explicitly require a specific comparator in its guidance and the use of a standard flu shot as a...
The Food and Drug Administration (FDA) has declined to review Moderna’s application for its investigational influenza vaccine, mRNA-1010, issuing a “refusal-to-file” (RTF) letter on . This decision, announced by Moderna, halts the agency’s initial assessment of the vaccine’s potential for approval.
According to Moderna, the FDA’s decision does not stem from concerns about the safety or efficacy of the mRNA-1010 vaccine. Instead, the RTF letter, signed by Vinayak Prasad, MD, MPH, director of the FDA’s Center for Biologics Evaluation and Research (CBER), cites the study design used to evaluate the vaccine. Specifically, the FDA determined that the comparator used in Moderna’s clinical trials – a licensed, standard-dose seasonal influenza vaccine – did not represent the “best-available standard of care.”
This determination is particularly noteworthy as the FDA did not explicitly require a specific comparator in its guidance and the use of a standard flu shot as a benchmark was previously discussed with CBER. Moderna CEO Stéphane Bancel expressed the company’s disappointment, stating, “This decision by CBER… does not further our shared goal of enhancing America’s leadership in developing innovative medicines.”
Clinical Trial Data
Moderna’s application was based on data from two Phase 3 clinical trials involving a total of 43,808 participants. The IGNITE P303 part C trial (NCT05827978) focused on adults aged 65 years and older, comparing mRNA-1010 to a high-dose influenza vaccine. The P304 trial (NCT06602024) included adults aged 50 years and older, comparing mRNA-1010 to a licensed, inactivated seasonal influenza vaccine. Both trials met all pre-specified primary endpoints and demonstrated statistical superiority for mRNA-1010 over the respective comparators.
Notably, Moderna points out that the efficacy demonstrated in the P304 study is comparable to that seen in trials supporting the approval of currently recommended influenza vaccines for older adults. These approved vaccines also showed statistically superior relative efficacy when compared to a standard-dose comparator.
Prior Guidance and Discrepancies
The current RTF letter appears to contradict previous communications between Moderna, and CBER. In , during a pre-Phase 3 consultation, CBER indicated that using a licensed standard-dose influenza vaccine as a comparator would be acceptable, although they recommended considering a vaccine preferentially recommended for those over 65. CBER did not raise objections to the study protocol before the trial began in , nor did they place the study on clinical hold.
Following the completion of the Phase 3 efficacy trial in , Moderna held a pre-submission meeting with CBER and received written feedback requesting additional analyses regarding the comparator. Moderna provided these analyses with its submission, including data from a separate Phase 3 trial comparing mRNA-1010 with a licensed high-dose influenza vaccine. Despite this, the FDA did not indicate it would refuse to review the application.
Looking Ahead
Bancel emphasized the importance of a thorough review, stating, “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.” Moderna has requested a Type A meeting with CBER to gain clarity on the rationale behind the RTF letter and to discuss the path forward for potential approval.
The FDA’s decision comes amidst a broader context of increased scrutiny over vaccine approvals under Health and Human Services Secretary Robert F. Kennedy Jr., a known vaccine skeptic. While the agency maintains that the refusal-to-file is based solely on the study design, the timing and the stated rationale have raised questions about the current regulatory landscape for mRNA vaccines.
The development of more effective influenza vaccines remains a critical public health priority, particularly for vulnerable populations like older adults. Moderna’s mRNA-1010 vaccine, with its demonstrated efficacy in clinical trials, represented a potential advancement in this area. The current situation underscores the complexities of the vaccine approval process and the importance of clear communication between pharmaceutical companies and regulatory agencies.