Study: Most accelerated approval indications don’t add high therapeutic value

Regulatory NewsRegulatory News
| 19 August 2022 | By Mary Ellen Schneider 

Less than half of the new drug indications approved through the accelerated approval pathway in the United States and the conditional marketing authorization pathway in Europe offered “high added therapeutic value,” according to an analysis of approvals from 2007 through 2021. A lower proportion of cancer indications were rated as having high therapeutic value, compared with non-cancer indications.
“Our study findings that many drugs granted accelerated approval or conditional marketing authorization did not appear to offer high added therapeutic value at the time of approval underscore the importance of timely completion of required postapproval studies for drugs and of ensuring that these confirmatory studies test clinically meaningful end points,” Kerstin N. Vokinger, MD, PhD, of the University of Zurich in Switzerland, and colleagues, wrote in JAMA Health Forum.
The US Food and Drug Administration’s (FDA) accelerated approval pathway offers expedited approval of new drugs to treat serious diseases based on surrogate endpoints that are “reasonably likely to predict clinical benefit.” The European Medicine Agency’s (EMA) conditional marketing authorization pathway is similar but is only available to first indications and such approvals are reviewed annually. The researchers noted that their findings support reform of the FDA’s accelerated approval pathway, including allowing the FDA to require initiation of confirmatory studies before accelerated approval and codifying expedited withdrawal procedures. (RELATED: Health policy experts call for stronger accelerated approval reforms, Regulatory Focus 6 July 2022)
In the analysis, the researchers used FDA and EMA databases to identify drugs granted accelerated approval in the US or conditional marketing authorization in the EU. They also identified drugs granted temporary authorization in Switzerland, an approval pathway launched in 2019 and considered equivalent to the EMA’s conditional marketing authorization. Therapeutic value ratings came from German, French, and Canadian health technology assessment agencies, which compared new medicines to existing therapies.
Over the 15-year study period, 146 drug indications (both first and supplemental indications) were granted accelerated approval in the US, 58 indications (all first indications) were given conditional marketing authorization by the EMA, and 13 indications (all first indications) were granted temporary authorization in Switzerland. Therapeutic value ratings were available for 90 drug indications in the US, 56 in the EU, and 11 in Switzerland.
Overall, 38.9% of accelerated approvals in the US and 37.5% of conditional marketing authorizations in the EU were rated as having high added therapeutic value at the time of approval. When the researchers considered reevaluations of the therapeutic value ratings based on post-approval evidence, the proportion of high-value approvals rose to 40.0% in the US and 39.2% in the EU. Among the 11 drug indications with a therapeutic value rating in Switzerland, just one was considered to have high added therapeutic value.
The researchers also considered how the therapeutic value ratings broke down between cancer indications and non-cancer indications receiving expedited approval in the US and Europe. Among cancer indications in the US, just 36.0% had a high added therapeutic value rating, compared with 53.3% for non-cancer indications. Similarly, 30.8% of cancer indications rated as having high added therapeutic value in the EU, compared with 52.9% for non-cancer indications.
“In some cases, these low ratings might be due to the uncertain nature of the data supporting the drugs approved through these pathways,” the researchers wrote. “Policy makers could consider increasing enforcement of timely postapproval study completion and reviewing the validating of surrogate measures used in these approvals.”
The study was supported by the Kaiser Permanente Institute for Health Policy, the Swiss Cancer Research Foundation, and a grant from the Swiss National Science Foundation. Of the researchers reported support from Arnold Ventures.
JAMA Health Forum


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you