Assessing the FDA’s Breakthrough Drug Program After Six Years

In the first four years of the U.S. Food and Drug Administration’s (FDA) breakthrough-therapy designation program, the agency approved 31 “breakthrough” drugs, but many were approved with limited evidence of added benefit, according to a health-policy report published in The New England Journal of Medicine.

The breakthrough-therapy designation program was created by Congress in 2012 to expedite testing and approval of medications that were intended to treat serious or life-threatening conditions, the authors, Jonathan J. Darrow, JD, MBA; Jerry Avorn, MD; and Aaron S. Kesselheim, MD, JD, MPH, explained.

Following Congressional orders, the FDA developed policies to reduce response timelines for medications with potential to perform better than existing treatments. The policy changes were effective, the authors wrote, with breakthrough drugs having an average 4.8-year development period (compared with 8.0 years for non-expedited therapies) and receiving approval a median of 1.7 months before their target review dates. However, many breakthrough drugs receive approval based on a single study, leaving their value over current therapies uncertain.

According to the authors, of the 31 breakthrough-designated therapies approved in the first four years of the program, 16 (52%) were approved based on phase I or II data, 14 (45%) were supported by only a single pivotal trial, and 13 (42%) were approved on the basis of either non–concurrently controlled or dose-comparison trials.

“When drugs are designated as breakthroughs and expedited through the FDA approval process with the use of substantial resources, many patients and physicians will reasonably expect such drugs to offer major advances,” the authors wrote, noting that “new drugs can meet technical requirements for the designation, and then be approved, despite having only modest efficacy.”

To avoid misleading patients about a new therapy’s efficacy, Drs. Darrow, Avorn, and Kesselheim suggest Congress eliminate the term “breakthrough” and “incorporate the most salutary breakthrough features, such as shortened response timelines, into the fast-track program.”

In an accompanying letter, FDA officials stated that the agency has accelerated the approval of drugs without compromising thoroughness.

Sources: Endpoints News, April 12, 2018; Darrow J, Avorn J, Kesselheim A. The FDA breakthrough-drug designation — four years of experience. N Engl J Med. 2018;378:1444-1453.