Breakthrough Therapy Designation is described on the FDA website as “a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).” It was signed into law in 2012, with the first full approval of a breakthrough designation candidate being only one year later. As of March 30, 2017, FDA has granted breakthrough therapy designation to 170 of the 505 total requests, and eventually approved 55 breakthrough therapy designated products.
The concept makes sense. If a new drug that aims to treat serious and life-threatening conditions shows unprecedented effect in early clinical trials, patients should not have to wait to receive treatment. A group called Friends of Cancer Research worked with partners in advocacy, regulation, drug development, and bipartisan congressional champions to take breakthrough therapy designation from concept to an expedited FDA development program. This ensures patient access to revolutionary drugs is as quick and effective as possible. A drug that receives breakthrough therapy designation is eligible for all FDA fast track features, intensive FDA guidance on an efficient development program (as early as phase 1), and organizational commitment involving FDA senior project managers.
FDA bases its decision to grant breakthrough therapy designation on scientific support for clinical endpoint(s). Studies that demonstrate a drug’s effect on a surrogate or intermediate clinical endpoint must be “adequate and well controlled” as required by the FD&C Act. Using surrogate or intermediate endpoints can save valuable time in the drug approval process. Consider an example of cancer patients. Rather than wait for a study to complete a potentially lengthy overall survival measurement, FDA may approve a drug based on evidence of tumor shrinkage, associated with a shorter measure such as progression-free survival, because it is considered reasonably likely to predict clinical benefit (and hence prolonged survival of patients).