The FDA Breakthrough-Drug Designation: Four Years of Experience

From the New England Journal of Medicine

By Jonathan J. Darrow, SJD, JD, MBA; Jerry Avorn, MD; Aaron S. Kesselheim, MD, JD, MPH

SUMMARY: This NEJM review evaluates the FDA breakthrough-therapy designation program, created by Congress in 2012 to accelerate testing and approval of drugs with potential for substantial improvement over existing treatments. Darrow, Avorn, and Kesselheim systematically examine the first four years of the program's operation, assessing which drugs received the designation, how many achieved full approval, and whether the program achieved its intended goals of speeding access to genuinely transformative therapies. The piece examines both successes and concerns, including whether the designation has been applied too broadly to drugs that do not ultimately demonstrate transformative benefit, and what the experience reveals about the tradeoffs between speed of approval and strength of evidence.

BACKGROUND: Congress created the FDA breakthrough-therapy designation in 2012 to expedite the testing and approval of medications with potential to provide substantial improvement over existing treatments.

KEY FINDINGS: The authors review the first four years of the program's experience, examining which drugs received the designation and how it affected their approval timeline and evidence requirements.

IMPLICATIONS: The breakthrough designation program offers lessons about how expedited regulatory pathways can be designed and monitored to ensure they serve genuinely transformative therapies rather than expanding access to drugs with insufficient evidence of benefit.