BDT designation: Real World Impact of Structural NoveltyAnother interesting one. More recent also (2020).
Created through the US FDA Safety and Innovation Act of 2012, Breakthrough Therapy Designation (BTD) was introduced to help shorten the development and review time of promising new drugs intended to treat serious or life-threatening diseases for which there is unmet medical need. The BTD approval pathway is distinct from other expedited development programs in that greater evidence of efficacy is required, but in return sponsors receive much more substantive engagement and support from the FDA during clinicial development. A key requirement for receiving BTD status is preliminary clinical evidence demonstrating substantial improvement on a clinically significant endpoint compared with other available therapies. Once designated as breakthrough therapies, investigational drugs receive intensive FDA guidance on an efficient drug development program, an organizational commitment to expedite the FDA development and review, and the potential eligibility, based on supporting clinical data, for rolling and priority review of the marketing application.
Receiving BTD status is considered a major accomplishment for any pharmaceutical R&D organization, bringing with it both public health and commercial benefits. Data shows that in addition to review periods being shortened by around three months, BTD drugs will also spend a total of two to three years less in pre-market development compared with non-BTD drugs. Furthermore, receiving this designation provides some credibility to the clinical promise of a given product and, as a result, can add significant value to a company. In fact, our analysis of publicly announced BTD grants found that the stock of publicly traded companies without any marketed products rose by an average of 6% (in excess of market returns) the day after BTD was announced.
The connection between chemical novelty and BTD
With such significant benefits, breakthrough therapy status remains a coveted but elusive prize. As of December 31, 2019, the FDA had received 817 total requests for Breakthrough Therapy designation since its inception. However, only around 40% of these requests were granted.
The breakthrough status for a given drug is not disclosed by the FDA until it receives final approval. Between 2013 and 2019, just 73 (26%) of the 276 new therapeutic drugs (NTDs) approved by the FDA's Center for Drug Evaluation and Research (CDER) were granted BTD status. Small molecules were the dominant drug modality, representing 56% of these breakthrough NTDs. A majority of these FDA-designated breakthrough small molecule drugs included at least one structurally novel new molecular entity (NME) whose shape and scaffold were not used in any previously FDA-approved drugs. However, a closer a look at the success rates for different types of small molecule drugs reveals some interesting findings.
Based on our recent analysis, approximately 3 in 10 structurally novel small molecule NTDs achieved breakthrough status compared with just 1 in 10 non-structurally novel small molecule NTDs. That means structurally novel drugs have been more than twice as likely to be granted BTD status by the FDA. This gap highlights the differential impact of structural novelty and the importance of pushing the boundaries of chemical space even further in the search for new drugs.