Breakthrough Therapies - A New FDA Paradigm

The flexibility promised in the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) continues to be rolled out at the Agency. FDASIA includes a provision that allows sponsors to request that their drug be designated as a "Breakthrough Therapy". FDA is in the process of developing guidance related to this designation, but Sponsors can now submit requests for Breakthrough Therapy designation. Presumably, breakthrough therapies will cover such agents as those which appear to provide unmet medical needs for important healthcare conditions.

Breakthrough therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. A breakthrough therapy designation conveys all of the current fast track program advantages, as well as more intensive FDA guidance on an efficient drug development program. The FDA also has an organizational commitment to involve senior management in such guidance.

FDASIA requires the following Agency actions, as appropriate:

  • holding meetings with the sponsor and the review team throughout the development of the drug
  • providing timely advice to, and interactive communication with, the sponsor regarding the development of the drug to ensure that the development program to gather the non clinical and clinical data necessary for approval is as efficient as practicable
  • taking steps to ensure that the design of the clinical trials is as efficient as practicable, when scientifically appropriate, such as by minimizing the number of patients exposed to a potentially less efficacious treatment
  • assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the cross-discipline members of the review team (i.e., clinical, pharmacology-toxicology, chemistry, manufacturing and control (CMC), compliance) for coordinated internal interactions and communications with the sponsor through the review division's Regulatory Health Project Manager
  • involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review

A request for Breakthrough Therapy designation can be submitted concurrently with, or as an amendment to, an Investigational New Drug Application (IND) with a cover letter, a completed form 1571, and the following information:

  • The proposed indications
  • A concise summary of information that supports the sponsor's breakthrough therapy designation request for the indication being studied, including:
    • The basis for considering the drug to be one intended to treat a serious condition
    • The preliminary clinical evidence that the drug may demonstrate substantial improvement over available therapies. A sponsor should describe the preliminary clinical evidence, including, for example, justification for the clinical study endpoint used and a brief description of statistical analyses

How has this been working? As of the end of March, 2013, there had been about 40 submissions for breakthrough therapy designation and about 10 had been granted. Incidentally, an Agency decision to approve, or to refuse to approve, and application for breakthrough designation is an action taken within the IND and remains confidential unless the Sponsor chooses to make it public.