Breakthrough Therapy Designation: Stakeholders Discuss the Program One Year Later

By James E. Valentine* & Alexander J. Varond –

Since the breakthrough therapy designation came into existence a year ago, drug companies (and their investors) have been trying to figure out the value of the program.  The designation was initially proposed as a way to accelerate the regulatory process for products that show early clinical evidence of substantial improvement over existing therapies.  Companies have had little guidance on how FDA makes this determination, since FDA does not make public its rationale for granting or denying individual requests for designation. 

To date, 24 drugs have received the breakthrough therapy designation (for a list,see here), and FDA has begun to shed light on how it plans to implement the program through the issuance of a draft guidance on all of the expedited drug review programs, including the breakthrough therapy designation program (we discussed the draft guidance in a previous post here). 

At a July 24, 2013 congressional briefing on breakthrough therapies and the other expedited drug review programs, a panel, moderated by Kate Rawson, a Contributing Editor at Prevision Policy, discussed FDA’s and industry’s current experience with the designation.  The panel consisted of CDER’s Janet Woodcock, representatives from J&J, Vertex, and Friends of Cancer Research, and a patient advocate from the Cystic Fibrosis Foundation.

An Overview of the Progress to Date

Although many more drugs have received the breakthrough therapy designation than the projected two to four drugs per year, Dr. Woodcock made no indication that the number was excessive and explained that the program was still in a transition phase.  She acknowledged that the newness of the program meant that even products that were in later stages of development (i.e., Phase 3) are being granted the designation despite the fact that the program was originally designed for drugs in early clinical development (i.e., Phase 1 and 2).  Some concern was expressed over whether FDA’s resources and attention were being diverted away from therapies without the designation, but the panelists agreed that it was too early to determine how the program would affect the agency in the long run.

J&J and Vertex, having both received early breakthrough therapy designations, agreed that the designation’s greatest value was that it prompted an “all-hands-on-deck” mentality at CDER.  This “all-hands-on-deck” approach brings together the needed review disciplines, including chemistry and manufacturing, and involves senior leadership early on.  The designation also provides more direct and collaborative engagement with the agency.

A Regulatory Approach to Keep Pace with Advances in Drug R&D

In certain therapeutic areas, drug research and development has changed dramatically over the past several decades.  FDA and industry agreed that drug companies have become better at leveraging the basic science underlying certain disease spaces to develop targeted, highly effective therapies.  Thus, a regulatory response was needed to keep pace with drug research and development.  The panelists agreed that breakthrough therapy designation represents an important step in the right direction, by speeding up the review of these highly effective therapies and increasing cooperation between FDA and industry.

New Rate-Limiting Factors Emerge

Dr. Woodcock noted that investigational drugs that receive breakthrough therapy designations should, in theory, be able to demonstrate efficacy with smaller, shorter, and fewer clinical trials.   The reduced time needed for clinical programs can render other development activities rate-limiting.  The panel identified manufacturing as one of the most important potential rate-limiting factors.  In response, the industry panelists indicated that FDA should be more flexible with its manufacturing requirements.  Meanwhile, FDA is looking for a more systematic solution that would utilize modern approaches to manufacturing.  Dr. Woodcock noted that for the last five to six months, FDA has been working on an internal effort to launch a new program to overhaul drug manufacturing in the United States.  Dr. Woodcock drew parallels to the two-year initiative launched in 2002, Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach (a.k.a. “21st Century Initiative”), but indicated that she would see to it that the new program would fare better than its predecessor.

Co-Development of Companion Diagnostics with Breakthrough Therapies

The panel noted that many of the targeted therapies likely to receive breakthrough therapy designations rely on companion diagnostics to identify their target patient subpopulations.  This raises the concern that the breakthrough therapy designation will provide little benefit if co-development of companion diagnostics does not have a similar expedited development program.  The industry panelists called for FDA to respond by expanding the “all-hands-on-deck” model to CDRH.

* Law student