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Inside Health Policy – Former FDA Official: Breakthrough Is Best FDASIA Option For Orphan Drugs

Inside Health Policy – Former FDA Official: Breakthrough Is Best FDASIA Option For Orphan Drugs


A former FDA orphan drug official and industry consultant called the recently created breakthrough designation the most “immediately useful”

of several provisions in the FDA Safety And Innovation Act that could benefit rare diseases, making the remarks following a product consultation meeting with FDA about using the new pathway. FDA’s top drug official said the agency has already received several inquiries about breakthrough designations and is working to create an application process for the new pathway.

Tim Cote, a former orphan drug official at FDA and the National Organization for Rare Disorders who now has a consulting firm, said the breakthrough designation is the most immediately useful provision in FDASIA because FDA is required to respond to those requests immediately. He said breakthrough designations are one of the three provisions in the law that could impact rare diseases, including accelerated approval and the pediatric rare disease review vouchers.

“I think it’s the most immediately useful,” he said. “And it appears that many, many companies should qualify for breakthrough. Breakthrough is basically offering companies that meet the criteria a little more FDA love.”

Cote said he had the first breakthrough drug consultation with FDA last month. The initial meeting was about an orphan drug and he expects to meet soon for other products.

Breakthrough designations expedite the development timeline for treatments of life-threatening diseases showing early clinical activity. FDASIA mandates FDA issue a draft guidance for the pathway within 18 months of the law’s enactment and a final draft guidance 12 months after it has collected comments, but Cote pointed out the provision is also self-executing. Therefore, the agency must respond to breakthrough applications within 60 days even before they have issued guidance or created an application process.

FDA drug center director Janet Woodcock told stakeholders at a Politico Pro briefing Monday (Oct. 1) that the agency has already received inquiries from companies seeking the breakthrough designation. Further some requests have been in areas FDA had not expected.

“We haven’t set up an application process, but we have people that are doing that now,” she told FDA Week. “We’ve received several inquiries around products that are promising. I think that rare diseases, obviously, is an area, but you’d be surprised that new science is moving into lots of areas. We are seeing things in areas that we didn’t think could be breakthroughs. That could really make a huge difference.”

She said the agency has seen drugs for untreatable diseases that are effective the first time they are used on patients. In those cases, subjecting the drugs to all of the traditional phases of drug development would be unethical, she said. The pathway may not immediately produce cures but it could change some life-threatening diseases into chronic conditions.

“People would still be dying, if we insisted that the initial treatments for HIV cured people,” she said. “The same with cancer. The intermediate goal for some cancers is to turn it into a disease you can live with other than dying.”

She said the ultimate goal would still be finding cures for the diseases, but another goal should be improving patients’ quality of life, which is something that FDA will also emphasize in its new benefit-risk framework (see related story).

Breakthrough designations will require the agency to rely more on patients to learn the natural history of rare diseases and find surrogate endpoints that can be used to determine whether the treatment is effective, Woodcock said.

Long term, Cote said the pediatric rare disease priority review voucher could prove to be the most substantive of the FDASIA provisions for rare diseases. He also said he was doubtful the law’s language on accelerated approval would affect drug development as it mostly encouraged FDA to use the pathway and did not provide additional authorities.

“There’s no additional authority, so to speak,” he said. “There’s a minor tweaking of the language. I just don’t see any real changes.”