FDA breakthrough therapy designation not associated with improved safety, efficacy

A breakthrough therapy designation led to faster FDA approval for new medications, although these agents did not show improved safety, novelty or efficacy compared with nonbreakthrough agents, study data showed.

Cancer therapies make up more than half of breakthrough-designated drugs that have been approved from the beginning of the FDA program through 2017.

“Despite the increasing frequency of breakthrough designations and approvals in oncology, the full implications of the breakthrough therapy program are not well understood,” Aaron S. Kesselheim, MD, JD, MPH, associate professor of medicine at Harvard Medical School, and colleagues wrote.

Gary H. Lyman, MD, MPH
Gary H. Lyman

Kesselheim and colleagues reviewed all new cancer drugs approved by the FDA from 2012 through 2017. The researchers evaluated possible associations between breakthrough designation and HRs for PFS, solid tumor response rates, serious adverse events and deaths that were not attributed to disease progression.

Fifty-eight new cancer drugs were approved by the FDA during the study period. Nearly half of these (43%; n = 25) were designated as breakthrough therapies.

Breakthrough-designated drugs had a median 5.2 years to FDA approval, compared with 7.1 years for nonbreakthrough designated drugs (P = .01).

However, breakthrough-designated drugs did not provide significantly greater median PFS gains compared with nonbreakthrough drugs (8.6 months vs. 4 months). The same was true of HRs for PFS (0.43 vs. 0.51) and response rates for solid tumors (37% vs. 39%).

Further, breakthrough-designated drugs were not more likely to use a novel mechanism (36% vs. 39%).

Breakthrough-designated drugs also demonstrated similar rates of death as nonbreakthrough designated drugs (6% vs. 4%) and similar rates of adverse events (38% vs. 36%).

The FDA should aim to simultaneously protect patients from adverse events and grant them timely access to potentially life-saving treatments, Nicole M. Kuderer, MD, oncologist at the Advanced Cancer Research Group in Seattle, and Gary H. Lyman, MD, MPH, researcher at Fred Hutchinson Cancer Research Center, wrote in an accompanying editorial.

“Although minimization of lengthy delays in approval of promising agents without major safety concerns is reasonable, rational drug approvals are needed to avoid future rationing of drug approvals,” Kuderer and Lyman wrote. “The development of clinically meaningful benchmarks for major disease settings will help focus FDA approvals on the most effective drugs.

“At the same time, careful ongoing evaluation of the impact of new regulatory models for expedited approval, such as presented in these studies, are essential,” they added. “Likewise, systematic engagement of regulators, clinicians and patients is needed to jointly nd solutions to better balance access to promising new agents and better protect patients from harm. Patients deserve no less than our best collaborative efforts.” – by Andy Polhamus

Reference:

Hwang TJ, et al. J Clin Oncol. 2018;doi:10.1200/JCO.2017.77.1592.

Disclosures: Kesselheim reports no relevant financial disclosures. Please see the study and editorial for all other authors’ relevant financial disclosures.

A breakthrough therapy designation led to faster FDA approval for new medications, although these agents did not show improved safety, novelty or efficacy compared with nonbreakthrough agents, study data showed.

Cancer therapies make up more than half of breakthrough-designated drugs that have been approved from the beginning of the FDA program through 2017.

“Despite the increasing frequency of breakthrough designations and approvals in oncology, the full implications of the breakthrough therapy program are not well understood,” Aaron S. Kesselheim, MD, JD, MPH, associate professor of medicine at Harvard Medical School, and colleagues wrote.

Gary H. Lyman, MD, MPH
Gary H. Lyman

Kesselheim and colleagues reviewed all new cancer drugs approved by the FDA from 2012 through 2017. The researchers evaluated possible associations between breakthrough designation and HRs for PFS, solid tumor response rates, serious adverse events and deaths that were not attributed to disease progression.

Fifty-eight new cancer drugs were approved by the FDA during the study period. Nearly half of these (43%; n = 25) were designated as breakthrough therapies.

Breakthrough-designated drugs had a median 5.2 years to FDA approval, compared with 7.1 years for nonbreakthrough designated drugs (P = .01).

However, breakthrough-designated drugs did not provide significantly greater median PFS gains compared with nonbreakthrough drugs (8.6 months vs. 4 months). The same was true of HRs for PFS (0.43 vs. 0.51) and response rates for solid tumors (37% vs. 39%).

Further, breakthrough-designated drugs were not more likely to use a novel mechanism (36% vs. 39%).

Breakthrough-designated drugs also demonstrated similar rates of death as nonbreakthrough designated drugs (6% vs. 4%) and similar rates of adverse events (38% vs. 36%).

The FDA should aim to simultaneously protect patients from adverse events and grant them timely access to potentially life-saving treatments, Nicole M. Kuderer, MD, oncologist at the Advanced Cancer Research Group in Seattle, and Gary H. Lyman, MD, MPH, researcher at Fred Hutchinson Cancer Research Center, wrote in an accompanying editorial.

“Although minimization of lengthy delays in approval of promising agents without major safety concerns is reasonable, rational drug approvals are needed to avoid future rationing of drug approvals,” Kuderer and Lyman wrote. “The development of clinically meaningful benchmarks for major disease settings will help focus FDA approvals on the most effective drugs.

“At the same time, careful ongoing evaluation of the impact of new regulatory models for expedited approval, such as presented in these studies, are essential,” they added. “Likewise, systematic engagement of regulators, clinicians and patients is needed to jointly nd solutions to better balance access to promising new agents and better protect patients from harm. Patients deserve no less than our best collaborative efforts.” – by Andy Polhamus

Reference:

Hwang TJ, et al. J Clin Oncol. 2018;doi:10.1200/JCO.2017.77.1592.

Disclosures: Kesselheim reports no relevant financial disclosures. Please see the study and editorial for all other authors’ relevant financial disclosures.