FDA refuses to review Moderna’s mRNA flu vaccine application

Moderna announced this evening that the Food and Drug Administration (FDA) has refused to initiate a review of its application for an mRNA-based seasonal influenza vaccine.

There are multiple reasons this announcement is unsettling. The loss of a possible mRNA option for flu is an obvious one. mRNA has already proven a fast and effective option to combat pathogens of pandemic potential. The possibility of adding it to the toolkit for influenza is no small thing. (And note that I am not advocating that the vaccine be licensed, since the data is not public. Only that it merits review.)

But there is a second implication that I find even more troubling. According to Moderna, FDA’s stated justification for the refusal (that the comparator vaccine does not reflect the best-available standard of care) does not square with the guidance that FDA had previously given the company. Typically, companies meet with FDA during the planning phase of clinical trials to understand the agency’s expectations. Indeed, Moderna says it got feedback from FDA at several points.

If a vaccine or biologic fails because it is not safe or effective, that’s one thing. That’s an expected part of drug development, and the reason why we have trials in the first place. But it’s not in anyone’s best interest for a trial to be invalidated because of study design. Drug development costs hundreds of millions of dollars and takes many years, all with no guarantee that the investment will pay off. For a product to make it all the way to regulatory review and get dismissed on a procedural basis is devastating. That’s what happened here, and at least according to Moderna, it occurred because FDA changed their expectations after the fact.

The consequences of a breakdown between developers and regulators cannot be overstated. Companies will not want to invest in R&D and clinical trials (often at-risk) if they don’t think they can get a fair regulatory review. Such unpredictability dramatically increases the risk of investing in product development to well beyond what will be bearable for most pharmaceutical companies. The natural outcome of such a scenario is companies walk away. And when companies walk away, it’s patients who lose access to the next generation of innovations.