FDA declines to review Moderna application for new flu vaccine

US regulators will not review Moderna’s request to license a new, potentially more effective flu shot – even though the US Food and Drug Administration (FDA) previously gave the green light to the project – in a decision that could have implications for all new and updated vaccines in the US.It’s the latest move from the Donald Trump administration against vaccines. Officials in January decided to stop fully recommending one-third of the routine childhood vaccines, including flu vaccines.“This is likely to discourage industry from investing in future influenza vaccines, and makes working with the US FDA uncertain and problematic,” said Dorit Reiss, professor of law at UC Law San Francisco.“They are refusing to review a new vaccine with a more flexible technology, while creating a real risk we will not have traditional vaccines for next year.”Messenger RNA, or mRNA, vaccines have shown the potential to be more effective at protecting against some illnesses, and they may also be updated more quickly than traditional egg-based flu vaccines – an important consideration since flu evolves quickly and may have pandemic potential.FDA officials will not review the evidence from Moderna’s clinical trials on the new mRNA flu shot because the trials compared Moderna’s shot to existing standard flu shots, rather than shots for high-risk individuals, according to a letter signed by Vinay Prasad, director of the Center for Biologics Evaluation and Research (CBER).The FDA does not consider the Moderna trial to be “adequate and well-controlled” because comparing the new shot to standard flu shots “does not reflect the best-available standard of care”, Prasad wrote.Yet Moderna did compare their vaccine against an existing high-dose flu shot in adults ages 65 and older; in adults under 65, they compared the new shot to standard flu vaccines.“For those under 65, the high dose is not standard of care,” Reiss said. “So their argument is also false.”The new vaccine elicited better antibody responses than the existing vaccines did, and no safety concerns were seen, the researchers found.Another Moderna trial, the results of which have not yet been published, compared the new vaccine against standard flu shots in adults ages 50 and older.The FDA issued a refusal-to-file letter, which means it will not consider the licensing application until Moderna provides more information. The letter did not specify which information it would require. It’s unusual for a refusal-to-file letter to be signed by the CBER director, as these are usually decisions made by the review team.There have been no public changes to rules and guidance on conducting clinical trials on vaccines. But in a leaked internal email in November, Prasad said the FDA would “revise the annual flu vaccine framework”, including the tests that show how well the vaccines work.The US Department of Health and Human Services (HHS) did not respond to questions about whether the FDA rules have changed and if the move represents a change in policy toward approving flu vaccines for everyone, not just those at risk.The decision “did not identify any safety or efficacy concerns” with the shot, Stéphane Bancel, Moderna’s chief executive, said in a statement. “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 asked the FDA for a meeting to discuss why the application was refused.“Combined with other steps, it shows FDA’s intent to make licensing vaccines for respiratory disease harder, without serious notice or consideration, and in ways that appear arbitrary,” Reiss said.The licensing application is already under review in the European Union, Canada, and Australia.In January, the HHS unilaterally changed its recommendation for children’s flu shots, recommending it only under “shared clinical decision-making” – a decision made without consulting outside vaccine advisers, medical providers, or the public.