FDA Gives and FDA Taketh Back: Rescinding Breakthrough Designation 
​​[Posted on: Thursday, April 26, 2018]

Since the inception of the Breakthrough Therapy Designation (BTD) program over 5 years ago, FDA granted this designation to 63 products, and approved 17 products under this program. But it also took back the designation from 14 of them, 5 in last year alone. That’s a whopping 22% of the BTDs; more than 1 out of 5 products granted BTD status lost it within 2-4 years. Amongst all the expedited approval pathways available from the FDA, BTD is the most coveted. The benefits of the BTD includes special attention by the review teams, quicker meetings, clinical protocol support, higher access to senior management, and the biggest of them all, approval based on fewer clinical trials. The market approval rate of BTDs is fairly high; literally all BTD products that reached the NDA or BLA stage got first-cycle approval. Getting a BTD is the most valuable independent proof of the credibility of a company’s data and the clinical promise of a given product. The successful granting of the BTD is cause for celebration. However, the bar for getting a BTD is very high. The product must demonstrate a very high benefit compared to the standard of care for a given indication, must be indicated for a life-threatening disease, and must fulfill an unmet medical need. Only one out of three BTD requests are granted; and it seems FDA is getting increasingly aggressive in enforcing the post-grant commitments. Once the BTD is granted for a product, it almost immediately results in realignment of the development program and requires periodic progress reports to the FDA. If the product failed to meet its projected goals, there are two options, either the company can voluntarily withdraw its BTD or the FDA can rescind it. In both cases, the net result is that the product loses all the incentives of the BTD. Last year’s 5 such cases are highest annual number in the short history of the BTD program. Last year FDA also granted fewer BTDs; 21 products were granted BTD status compared to 28 the year before, a drop of 25%. It is obvious that FDA believes this is a very important program and must be made available to the most deserving products. What may be a deserving candidate today may not stay that way over time. This is unlike any other expedited programs, where FDA does not rescind the designation as quickly. The most likely reason is that the BTD is the most resource-draining status for the FDA review teams. The review teams are required to make time within a short period for review of the BTD product-related information which could strain the timelines for other products. Therefore, when the developers default on their promise, FDA is brutally efficient in taking back the designation. And that’s the way it should be. The BTD program was created specifically to expedite “exceptional” products at early stages of development so that patients could have access to therapies that otherwise would take a much longer time. The last few years have seen some really outstanding drugs come to market early via this pathway so it makes sense that FDA is protective of keeping the status of this program as the one that promotes such products. Sponsors must understand that they cannot lax after getting BTD and they need to move faster just like the FDA, or the BTD may be lost. The product can still stay in development as a conventional product and may still come to market eventually, but it would have to do that on normal timelines, not expedited.