Rumbling beneath the Trump administration’s hostility toward mRNA vaccines has been a larger question of whether the FDA will eventually pull them from the market altogether.
According to experts, probably not. But that doesn’t mean the agency won’t act in other ways to curtail them, and its recent treatment of Moderna’s mRNA flu vaccine application could provide a clue about how that might happen.
“I think FDA will be a lot more likely to put obstacles in the way of approving new versions — which would be bad enough — than remove existing vaccines,” vaccine law expert Dorit Reiss, professor of law and chair in litigation at UC Law San Francisco, told PharmaVoice via email. “And their recent conduct suggests they may well do it in an inconsistent, under-handed way: Agree to a certain set of trials for approval, and then go back on their word.”
That’s apparently what happened when the FDA declined to review Moderna’s biologics license application for its mRNA seasonal flu vaccine, a decision it reversed eight days later.
The company said the agency’s sole reason for the refusal was trial design.
“CBER does not consider the application to contain a trial ‘adequate and well controlled’ and the application is therefore, on its face, inadequate for review,” the FDA wrote in a refusal-to-file letter. “This is because your control arm does not reflect the best-available standard of care in the United States at the time of the study.”
However, Moderna claimed the agency had already OK’d the trial design, stating that the refusal “is inconsistent with feedback at pre-phase 3 and pre-submission consultations” and “previous written communications from CBER to Moderna.”
“At no time in the pre-submission written feedback or meeting did CBER indicate that it would refuse to review the file,” according to Moderna’s statement.
Additionally, the RTF letter didn’t cite safety or efficacy concerns.
A high standard
A lot needs to happen for an already approved vaccine to be removed from the market.
“[T]here's a high standard for removal,” according to Reiss, including evidence of significant safety or manufacturing problems, hearings and other processes. Without such evidence, manufacturers would certainly raise legal challenges.
“You need to meet procedural requirements and show that the removal was not arbitrary and capricious,” Reiss previously told PolitiFact. "Manufacturers may well sue if they disagree. If there is no sufficient justification, [they] may win in court against the revocation."
The standard is a bit different for drugs granted accelerated or emergency approval. There are many examples in recent years of drugs that have had accelerated approvals withdrawn, including the preterm birth drug Makena in 2023.
The FDA used this standard in August when it revoked emergency authorizations for COVID-19 vaccines, limiting use in certain age groups despite noting that “safety concerns were not the basis for FDA's decision.”
Additionally, the FDA appeared to throw wrenches into what’s long been the standard approval process for annually updated vaccines, revealing a plan last year to require placebo testing for all new vaccine approvals, raising questions about what might be considered “new.”
It also delayed full approval for Novavax’s COVID-19 vaccine, asking the company to provide a post-market commitment for additional clinical data. FDA Commissioner Dr. Marty Makary wrote on X, “This is a new product that Novavax is trying to introduce to the market with a study of a different product from 2021. New products require new clinical studies.”
Eventually, it may make good on those threats.
“Since manufacturers have been updating the mRNA vaccines, that would mean that a new, updated version will not get approval,” Reiss said.
A chilling effect
The FDA’s reversal of its refusal to review Moderna’s vaccine application came after the company proposed an age-based regulatory pathway and a post-marketing requirement to conduct an additional study in older adults. An approval decision is expected by August.
The damage may already be done though. The FDA’s recent sparring with Moderna is only the latest in a consistent string of moves by HHS Secretary Robert F. Kennedy Jr. and the Trump administration to limit access to vaccines, particularly those using mRNA technology, and sow safety doubts. In August, for example, the HHS said it was canceling nearly $500 million in contracts to develop mRNA vaccines.
That sentiment has spread beyond Washington, with four GOP candidates for Iowa governor supporting an mRNA vaccine ban.
These moves have forced some pharma companies to shift strategies. Moderna CEO Stéphane Bancel said in January that the company would no longer invest in late-stage vaccines trials because of the current environment. In its latest earnings document, Sanofi said it has discontinued development of a next-generation mRNA seasonal flu vaccine.
The drugmaker Invivyd, which is testing a preventative option for COVID-19 against existing mRNA covid vaccines, said the FDA has asked it to specifically monitor adverse events relevant to mRNA COVID vaccines in a phase 3 trial, citing the rare risk of myocarditis in the young adult population.
“No similar requests have been made for other Invivyd clinical trials without an mRNA COVID vaccine arm,” the company said.
