I Regret to Inform You that the FDA is FDAing Again

I had high hopes and low expectations that the FDA under the new administration would be less paternalistic and more open to medical freedom. Instead, what we are getting is paternalism with different preferences. In particular, the FDA now appears to have a bizarre anti-vaccine fixation, particularly of the mRNA variety (disappointing but not surprising given the leadership of RFK Jr.).

The latest is that the FDA has issued a Refusal-to-File (RTF) letter to Moderna for their mRNA influenza vaccine, mRNA-1010. An RTF means the FDA has determined that the application is so deficient it doesn’t even warrant a review. RTF letters are not unheard of, but they’re rare—especially given that Moderna spent hundreds of millions of dollars running Phase 3 trials enrolling over 43,000 participants based on FDA guidance, and is now being told the (apparently) agreed-upon design was inadequate. [...]

In context, this looks like the regulatory rules of the game are being changed retroactively—a textbook example of regulatory uncertainty destroying option value. STAT News reports that Vinay Prasad personally handled the letter and overrode staff who were prepared to proceed with review. Moderna took the unusual step of publicly releasing Prasad’s letter—companies almost never do this, suggesting they’ve calculated the reputational risk of publicly fighting the FDA is lower than the cost of acquiescing.

Moreover, the comparator issue was discussed—and seemingly settled—beforehand. Moderna says the FDA agreed with the trial design in April 2024, and as recently as August 2025 suggested it would file the application and address comparator issues during the review process.

Finally, Moderna also provided immunogenicity and safety data from a separate Phase 3 study in adults 65+ comparing mRNA-1010 against a licensed high-dose flu vaccine, just as FDA had requested—yet the application was still refused.

What is most disturbing is not the specifics of this case but the arbitrariness and capriciousness of the process. The EU, Canada, and Australia have all accepted Moderna’s application for review. We may soon see an mRNA flu vaccine available across the developed world but not in the United States—not because it failed on safety or efficacy, but because FDA political leadership decided, after the fact, that the comparator choice they inherited was now unacceptable.

The irony is staggering. Moderna is an American company. Its mRNA platform was developed at record speed with billions in U.S. taxpayer support through Operation Warp Speed — the signature public health achievement of the first Trump administration. The same government that funded the creation of this technology is now dismantling it. In August, HHS canceled $500 million in BARDA contracts for mRNA vaccine development and terminated a separate $590 million contract with Moderna for an avian flu vaccine. Several states have introduced legislation to ban mRNA vaccines. Insanity.

The consequences are already visible. In January, Moderna’s CEO announced the company will no longer invest in new Phase 3 vaccine trials for infectious diseases: “You cannot make a return on investment if you don’t have access to the U.S. market.” Vaccines for Epstein-Barr virus, herpes, and shingles have been shelved. That’s what regulatory roulette buys you: a shrinking pipeline of medical innovation.

An administration that promised medical freedom is delivering medical nationalism: fewer options, less innovation, and a clear signal to every company considering pharmaceutical investment that the rules can change after the game is played. And this isn’t a one-product story. mRNA is a general-purpose platform with spillovers across infectious disease and vaccines for cancer; if the U.S. turns mRNA into a political third rail, the investment, talent, and manufacturing will migrate elsewhere. America built this capability, and we’re now choosing to export it—along with the health benefits.

by Alex Tabarrok, Marginal Revolution |  Read more:

Image: Brian Snyder/Reuters

[ed. See also: F.D.A. Refuses to Review Moderna Flu Vaccine (NYT).]