Rethinking the Value of FDA Breakthrough Designation

In a recent video interview with Applied Clinical Trials, Meri Beckwith, Co-CEO, Lindus Health, discussed the evolving perception of breakthrough designation amid the FDA’s recent Complete Response Letters (CRLs) issued to Replimune and Capricor. He emphasized that breakthrough designation does not necessarily guarantee approval, but offers quicker decision access and investor signaling. Beckwith also stressed the importance of agility in trial design, advocating for adaptive trials and control groups where ethical. To mitigate regulatory unpredictability and avoid costly CRLs, he highlighted the need for future-proofing trial protocols with adaptive randomization and synthetic control groups.

ACT: How has the industry’s perception of breakthrough designation evolved, and do you think it’s led some sponsors to over-prioritize speed to designation over the rigor required for final approval?

Beckwith: The industry's confidence, or perceived value of a breakthrough designation, has definitely taken a hit after the last few weeks. However, if you dig under the surface, the breakthrough designation was never about, if you receive a breakthrough designation, it doesn't mean your drug is more likely to be approved. The FDA has always been super clear about drugs with the breakthrough designation being subject to the same rigorous level of review as those without a breakthrough designation. It really is just about access to a slightly quicker decision. I think that is what it is. I also think perhaps that companies pursue it, not just because of the timeline benefits, but also because of the signaling to investors. Beyond just that shortened review timeline, it does have a certain kind of cache, it gets your company better visibility with investors. If you're listed, it's a great news flow item to put out. I think there's a few reasons companies pursue it, but I don't think anyone really sees it as something that's more likely to make your therapy approved.