The first step towards solving a problem is to identify that a problem exists.
The breakthrough therapy provision in FDASIA is aimed at shortening the development time for drugs intended to treat serious or life-threatening conditions and for which preliminary clinical evidence suggests a substantial improvement over existing therapies. But the devil is in the developmental details.
But the promise of speeding innovative medicines to market could be blunted unless issues related to manufacturing, companion diagnostics and international harmonization are adequately addressed.
That was the message from a multi-stakeholder panel discussion at the November 14th Conference on Clinical Cancer Research, co-sponsored by the Friends of Cancer Research and the Engelberg Center for Health Care Reform at Brookings.
Panelists and FDA representatives agreed that if a drug is ushered through the development process, hold-ups will arise from other areas. As a result, discussions surrounding chemistry, manufacturing and control issues for new drugs and biologics will need to take place much earlier in the clinical development process than currently happens to avoid a situation where a breakthrough therapy is approved but the manufacturing processes are not in place to support commercial marketing.
Discovery is one thing. Development and commercialization are another. Nobody said it was going to be easy.
Breakthrough treatments that require companion diagnostics also could be potentially problematic, as the development, validation and approval of the diagnostic may not be able to keep pace with the drug’s abbreviated clinical development program.
Under FDASIA, sponsors must request that their product be designated as a breakthrough therapy, and FDA must respond within 60 days. For drugs receiving the designation, the agency must work in a variety of ways to expedite the products’ development and review, including providing timely advice to the sponsor to ensure the development program is as efficient as possible and involving senior managers and experienced review staff in a collaborative cross-disciplinary review.
Under the law, FDA must issue draft guidance by January 2014 on the process and criteria for making designations and actions the agency will take to expedite development and review.
What about international harmonization? During the development of the FDASIA legislation, Woodcock cited the need for FDA and EMA to “be on the same page” about abbreviated development programs for breakthrough therapies. And, according to a conference issues brief, absent an equivalent development pathway in the EU, “drugs that receive breakthrough designation in the U.S. may still be required to go through the traditional drug development pathway for EMA approval. These differing requirements may make the breakthrough pathway an unattractive option for drug sponsors.’
Richard Pazdur raised the question as to what happens when subsequent studies of a breakthrough-designated product fail to confirm the encouraging efficacy signal seen early in development. Bob Temple suggested the agency’s guidance on breakthrough designations would account for such a scenario. “The concept clearly includes the possibility that it looked really good at first and then now it doesn’t and so it’s designation could go away,” he said. “I’m sure there will be a provision for that.”
That's one thing we can most certainly be sure of. Caveat emptor.