The FDA’s Breakthrough Therapy Program By the Numbers

Published: Jan 05, 2015

The FDA’s Breakthrough Therapy Program By the Numbers
December 31, 2014
By Riley McDermid, BioSpace.com Breaking News Sr. Editor

The two-year-old Breakthrough Therapy program initiated by the U.S. Food and Drug Administration to speed up approval and availability of groundbreaking therapies has seen widespread success, an analyst with Evercore ISI said Wednesday.

Mark Schoenebaum, a medical doctor and biotech analyst with Evercore ISI, parsed data from the FDA for its first two years of the Breakthrough Therapy program.

“According to the FDA, the biggest factor in deciding to grant BTS is the ‘magnitude of the treatment effect.’ Also according to FDA documents, the successful requests ‘in general’ showed a reduction in the risk of the event of interest of ‘over 50 percent,’” he said.

He found that within the Center for Drug Evaluation and Research, there have been 206 applications for BTS (Breakthrough Therapy Status), of which 62 have been granted and 101 have been denied (two were withdrawn). Within the Center for Biologics Evaluation and Research, there have been 37 applications, of which 27 were denied and 7 granted.

“Bear in mind these stats are dynamic,” said Schoenebaum, “thus many of the 206 applications are presumably still being evaluated.”

In 2013, three drugs granted BTS were approved: Gazyva for CLL, Imbruvica and Sovaldi. In 2014, there have been nine approvals (4/9 for non-cancer applications): Kalydeco, Arzerra supplement for CLL, Zykadia, Zydelig, Imbruvica supplement for CLL, Promacta supplement for aplastic anemia, Keytruda, Ofev and Esbrient. One BTS drug was denied approval (Serelaxin).

“If the endpoint is survival, the FDA specifically notes that ‘lesser improvements’ could be adequate. The FDA has emphasized, however, that a specific efficacy ‘bar’ probably isn't possible to precisely identify ‘because of the wide range of conditions and endpoints studied,” said Schoenebaum. “That said, FDA has stated that ‘in general, improvements of 10 percent over comparator do not seem to be BT territory.’"

According to the FDA, factors that favored granting of BTS include higher enrollment, more and larger phase trials, and applications that have a "genetic/targeted" component. Specifically, the median trial enrollment for granted/denied applications was 88/51; the maximum trial phase for granted/denied applications was 1.94/1.73; the trial count was 1.53/1.23; and the granted/denied rates for applications with/without a genetic or targeted component was 38 percent/20 percent.

“Perhaps surprisingly, successful applications were more likely than denials to have some form of alternative therapy available for the disease,” noted Schoenebaum.

Factors which did not appear to influence likelihood of success included rare/orphan status and existence of randomized trial evidence.

“Most denied applications were turned down for trial ‘design’ and trial "data" issues. In 66 percent of the denials, FDA cited ‘lack of efficacy,’” he said. “In 16 percent, the agency cited "lack of safety." 43 percent of denied applications exhibited ‘trial design flaws.’"

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