Moderna navigates a sharply divergent regulatory and commercial landscape for its respiratory vaccine portfolio as FDA declines to review its next-generation influenza shot while the company simultaneously deepens its manufacturing and supply ties with the Mexican government.

The FDA’s Center for Biologics Evaluation and Research (CDER) issued a Refusal-to-File letter for Moderna’s biologics license application for the company’s investigational influenza vaccine mRNA-1010. The agency said it would not initiate review of the application, despite Moderna having exercised a Priority Review Voucher to expedite the process.

According to Moderna, the letter (signed by CBER Director Vinayak Prasad, MD, MPH) identified the choice of a licensed standard-dose seasonal influenza vaccine as the comparator in a Phase III study as the sole reason for refusing to file the application.¹

The agency cited the lack of an “adequate and well-controlled” study using a comparator that “does not reflect the best-available standard of care.” The letter did not identify any safety or efficacy concerns related to mRNA-1010.

Moderna argues that neither the applicable regulation, 21 C.F.R. § 314.126, nor FDA guidance on seasonal influenza vaccines references a requirement that comparators reflect the “best-available standard of care.”¹

The company also pointed to prior written communications (such as in April 2024, during a pre-Phase 3 consultation), CBER stated that “while we agree it would be acceptable to use a licensed standard dose influenza vaccine as the comparator in your Phase III study, we recommend you use a vaccine preferentially recommended for use in older adults by the ACIP (i.e., Fluzone HD, Fluad or Flublok) for participants >65 years of age in the study.”¹

The agency added that if Moderna proceeded with a standard-dose comparator in adults aged 65 or older, it agreed with the company’s plan to include appropriate disclosures in the informed consent form.¹ Moderna said no clinical hold comments were raised before the study began in September 2024.

After completing the Phase III efficacy trial in which mRNA-1010 met all pre-specified primary endpoints, Moderna held a pre-submission meeting with CBER in August 2025. The agency requested additional analyses on the comparator, calling it a “significant issue during review of your BLA.” Moderna said it provided those analyses, including data from a separate Phase III study comparing mRNA-1010 with a licensed high-dose influenza vaccine.¹

At no point, the company said, did CBER signal that it would refuse to review the application.

“This decision by CBER, which did not identify any safety or efficacy concerns with our product, does not further our shared goal of enhancing America's leadership in developing innovative medicines,” said Stéphane Bancel, chief executive officer of Moderna. “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 BLA includes two Phase III studies enrolling upwards of 43,808 participants, with one evaluating safety and immunogenicity in adults aged 65 years or older against a high-dose comparator, and the other assessing the safety and relative efficacy in adults aged 50 years or older using a licensed standard-dose comparator.¹ In both trials, Moderna reported statistical superiority versus the respective comparators on primary endpoints.

Following the refusal letter, Moderna has requested a Type A meeting with CBER to clarify the path forward. The company says it does not expect the Refusal-to-File decision to affect its 2026 financial guidance.¹

Meanwhile, mRNA-1010 has been accepted for review in the European Union, Canada, and Australia, with potential approvals in those regions expected beginning in late 2026 or early 2027, subject to ongoing review.¹

Why did Moderna enter an agreement with the Mexican government?

While the company deals with regulatory issues in the United States, Moderna is advancing a parallel strategy to expand international manufacturing and supply, underscored by a newly signed five-year Memorandum of Understanding with the Mexican government.

Under the agreement, Moderna will collaborate with Mexico’s Laboratorios de Biológicos y Reactivos de Mexico and Laboratorios Liomont to support “Plan Mexico,” a national initiative aimed at strengthening domestic biopharmaceutical manufacturing and health security.²

The partnership includes supply of Moderna’s respiratory vaccine portfolio and a technology transfer to Liomont to enable local production of mRNA-1273, the company’s Covid-19 vaccine, establishing in-country manufacturing capacity.

“We are proud to support Mexico in its mission to strengthen national health security,” Bancel said. “Through this agreement, we will be able to provide the Mexican people with access to our respiratory vaccines and critical pandemic response capacity. This collaboration also reflects the growing demand for these vaccines in Mexico, and we are excited about the opportunity to support public health needs while driving sales growth through geographic diversification.”

The agreement follows approval by Mexico’s Federal Commission for the Protection against Sanitary Risk of Moderna’s 2025–2026 Covid-19 vaccine for individuals aged six months and older, as well as a purchase adjudication for up to 10 million doses for the upcoming season.²

Sources

1. Moderna Receives Refusal-to-File Letter from the U.S. Food and Drug Administration for Its Investigational Seasonal Influenza Vaccine, mRNA-1010 Moderna February 10, 2026 https://feeds.issuerdirect.com/news-release.html?newsid=7346090610333866&symbol=MRNA
2. Moderna to Enter into Long-Term Strategic Agreement with the Government of Mexico Moderna February10, 2026 https://feeds.issuerdirect.com/news-release.html?newsid=4806394309889623&symbol=MRNA