Two studies published in the Journal of Clinical Oncology are calling into question the value of the U.S. Food and Drug Administration's (FDA's) breakthrough-therapy designation program. While drugs receiving the designation reached market an average of nearly two years earlier than non-breakthrough treatments, breakthrough drugs performed similarly or worse on several key performance indicators.
Breakthrough-therapy designation, enacted by Congress in 2012, provides for expedited review of drugs indicated to treat serious or life-threatening conditions. The drug must demonstrate the likelihood of significant improvement over existing treatments, but does not require support from a randomized, controlled trial (RCT).
The first study published in the journal demonstrates that the time to FDA approval for breakthrough drugs was nearly two years shorter than those that did not receive the designation (p=0.01), but also showed that rates of progression-free survival, death, serious adverse events, and objective response rates in solid tumors were similar regardless of breakthrough status.
The second analysis concluded that drugs approved without support from RCTs were more likely to require post-approval label modifications than drugs approved with RCT evidence (p<0.001). In addition, therapies approved without this type of evidence were more likely to require a companion diagnostic test (p=0.02), receive breakthrough designation or accelerated approval (p<0.001), and have surrogate endpoints as primary outcomes (p<0.001)
In an editorial accompanying these studies, authors Nicole M. Kuderer, MD, and Gary H. Lyman, MD, cautioned the FDA against sacrificing patient safety for a speedy review process. "The FDA needs to first and foremost protect patients from serious adverse drug effects while it provides reasonable and timely access to promising new therapies for life-threatening conditions," they wrote. "Especially those patients for [whom] few remaining options exist.”
Source: MedPage Today, June 20, 2018; Journal of Clinical Oncology, June 20, 2018; FDA Fact Sheet, March 28, 2018.