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Inside Health Policy – FDA Official: Breakthrough Designation Brings High Bar, Costly Investment

Inside Health Policy – FDA Official: Breakthrough Designation Brings High Bar, Costly Investment


The head of FDA’s office of new drugs warned drug companies looking to use the newly created breakthrough therapy designation that they will face a “high bar”

 compared with priority reviews and the process will require significant investment from both the agency and sponsors. Those companies that do qualify for the designation could see clinical timelines speed up so significantly that they might be left unprepared to manufacture the product, the official cautioned.

Upcoming draft guidance outlining and clarifying the expedited approval pathways available to sponsors, along with initial applications for drugs seeking the breakthrough therapy designation, will chart the new pathway created by the FDA Safety and Innovation Act, including how much clinical data will be required and if the designation can be revoked, said John Jenkins, director of the office of new drugs.

Jenkins, speaking at the U.S. Conference on Rare Disease and Orphan Products on Monday, stressed the breakthrough designation is not meant for drugs that would normally meet the agency’s definition of priority review.

“This is all hands on deck,” Jenkins said of the new designation. “This is a result that is so impressive, so unexpected, it would have such a dramatic impact on the treatment of patients with that disease, that both FDA and the sponsor, everyone should put all the resources into discussing how to expedite that drug if, and I put in there that if, that promise holds up through the formal drug development program.”

The breakthrough designation, established in the recently enacted FDASIA law, expedites the development timeline for treatments with life-threatening diseases showing early clinical activity. A former FDA orphan drug official and industry consultant recently called the designation the most “immediately useful” of several rare disease provisions in FDASIA (see FDA Week, Oct. 5).

Jenkins said the new designation will likely be of great commercial value to companies, who can tell investors that FDA has designated their drug as “breakthrough” but again cautioned that the agency views the designation as only applying to products that show a “significant breakthrough in a disease area.”

“It is possible that companies will try use it to get a designation and market it to the investment community for their financial reward in gaining the money to do the investment program,” he said, noting that companies have used the fast track designation in the past to raise money.

Further, he said companies must keep in mind that the breakthrough designation could speed up the entire development timeline, with the possibility that the designation could truncate the clinical program so significantly that the clinical program is completed but companies are not ready to manufacture the product.

“They also have to think about their manufacturing plans and their ability to make the product,” he said. “We could get ahead of their ability to make the product.”

Jenkins said the agency has already received several applications for the newly created pathway and is currently reviewing those applications. Under the law, the agency has 60 days to decide if a drug is eligible for the breakthrough designation.

Jenkins said these initial applications will help FDA define the breakthrough designation, adding that the law says the new designation must be based on clinical data but it does not detail how much data is needed. Jenkins said that means companies could attempt to base their application on two patients where one had a 50 percent response rate, and FDA must decide if that is what is meant by “breakthrough.” He said the agency will have to review each case to determine if it meets the criteria for breakthrough designation.

“We are likely to see some people who view their product as breakthrough where we may not view it as breakthrough,” he said.

Further, Jenkins said the agency plans to put out new comprehensive guidance to clarify the various expedited pathways for drugs, including the breakthrough designation. He said there is confusion about the pathways and differences in statutory language used for different designations. For example, some provisions use “existing therapy” while some use “available therapy” and there is confusion over whether those terms have the same meaning.

“The idea is to try to clarify these pathways so people can understand and use them appropriately,” he said.

Jenkins said the guidance could clarify parts of the breakthrough statute, which does not specify if FDA can revoke the breakthrough designation. For example, he said a company could be developing a cancer drug and see a dramatic response in patients when conducting a safety trial, leading the sponsor to apply for breakthrough designation.

“That could be the clinical data that could support a breakthrough designation but we have to decide how robust does that information look or does it look like a chance finding that is not going to hold up over time,” Jenkins said.

Beyond the breakthrough designation, Jenkins also outlined the FDASIA provisions designed to speed up drug approvals, including for rare disease treatments. Jenkins said the increased amount of meetings and transparency under the new law creates a “major change in the culture” of how FDA reviews applications. He said this also will be a major change for sponsors, who must decide how they handle the increase in information from FDA.

Jenkins previously complained that some venture-backed companies issue public statements that are “overly optimistic” and may not capture the nuance of FDA advice, while the agency is constrained in monitoring and responding to these statements (see FDA Week, Dec. 23, 2011)

“It is going to be a culture change for the community at large: how much of this information gets transmitted from the applicant out to the community through press releases or investment reports, etc., and how accurate those interactions with the agency are communicated to the public,” he said.