Moderna Inc (MRNA)

[axelvento]

After the FDA's surprise refusal to take up a review of Moderna's next-gen flu vaccine, the public disagreement between U.S. regulators and the mRNA specialist took a new turn Wednesday, with the U.S. Department of Health and Human Services (HHS) sharing further rationale behind the decision.

"The FDA rejected Moderna's application for filing because the company refused to follow very clear FDA guidance from 2024 to test its product in a clinical trial against a [Centers for Disease Control and Prevention (CDC)]-recommended flu vaccine to compare safety and efficacy," HHS spokesperson Andrew Nixon said in a statement.

"Moderna exposed participants age 65 and over to increased risk of severe illness by giving them a substandard of care against the recommendations of FDA career scientists," the statement continued.



The HHS spokesperson went on to note that the vaccines conferring the highest protection to seniors are a "subset of high-dose flu shots recommended by the CDC Advisory Committee on Immunization Practices, which would have served as the proper control in this study."

The justification came after Moderna disclosed late Tuesday that it received an FDA refusal-to-file letter (PDF) for mRNA-1010, its next-gen mRNA seasonal flu vaccine. In declining to review the application, the FDA took issue with Moderna's decision to test a standard-dose influenza vaccine in older adults enrolled in the trial's control arm rather than a high-dose shot.

The company issued an unusually public rebuke of the agency's rationale, saying that in 2024, the FDA didn't raise the standard-dose vaccine as a deal-breaker during trial design discussions. But in a note to clients after the disclosure, Citi analysts suggested that the changing of the guard at the FDA following the 2024 election—and subsequent comments from agency leaders—should have made it clear that the comparator arm plan could raise an issue.


After discussing the situation with Moderna management, TD Cowen analysts wrote to clients that the RTF letter "appears to deviate from historical review practices and seems unreasonably stringent, in our opinion."

Leerink Partners' analysts took it a step further, saying the FDA's decision "reflects the 'maximum pressure' footing vis-a-vis mRNA vaccines by current HHS/FDA leadership." For their part, the analysts said they had flagged the "increasingly likely" chance of an "adverse outcome" for the mRNA seasonal flu program given the trial's design and the "FDA’s hardening regulatory stance," according to a Wednesday note to clients.

As the Leerink team noted, the decision shouldn't come as a complete surprise. For one, high-level decision-makers in the U.S. government have made very public anti-mRNA overtures at various points during the first year of the Trump administration.


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HHS in August abruptly ended mRNA vaccine work funded by the Biomedical Advanced Research and Development Authority. The following month, HHS Secretary Robert F. Kennedy Jr. appeared at a Senate hearing and took issue with the rollout of mRNA COVID-19 shots, alongside endorsing false information about the shots' safety.

In fact, the changing vaccine landscape in the U.S. has prompted Moderna to pivot its strategy to focus more on oncology. As vaccine hesitancy has reached the heights of U.S. healthcare policymaking, it has prompted recent criticism from the CEOs of Pfizer and Sanofi.

For Moderna, the RTF letter puts future projected sales related to its COVID-flu combo shot "in doubt," Leerink's team said, and it "imperils" the company's break-even guidance for 2028. The setback further "prolongs reliance on COVID sales in the face of eroding demand," the analysts explained.

https://www.fiercebiotech.com/biotech/after-facing-modernas-ire-fda-stands-behind-decision-spurn-mrna-flu-filing