The FDA is faster to approve new oncology therapies compared with the European Medicines Agency (EMA); but that speed may have consequences.
New oncology therapies receive earlier market authorization in the United States than Europe with shorter review times from the FDA compared with the European Medicines Agency (EMA), according to a study published in JAMA Network Open.
The cross-sectional study reviewed FDA and EMA regulatory databases to identify new oncology therapies approved in both the United States and Europe from 2010 to 2019. Although their approval processes are different, there is “a close alignment between FDA and EMA in more than 90% of new therapy registrations across all therapeutic areas,” the authors explained.
The timing of regulatory activities was characterized through an examination of initial market authorization date, submission dates, review length, and approval timings relative to publication of clinical studies.
The study found that 95% of 89 new oncology therapies approved in the United States and Europe were approved in the United States before receiving European market authorization. Median review times for the FDA (200 days) were more than half that of the EMA (426 days).
Drug manufacturers continue to submit regulatory documents to the FDA earlier than the EMA. The FDA received new drug licensing applications a median of 20 days earlier than the EMA, the study found. However, the proportion of manufacturers who submitted new market authorization applications to the FDA prior to the EMA has fallen from 80% between 2003 and 2010 to 72% from 2010 to 2019.
Submissions to the EMA contained more complete and less preliminary data due to later submission times, despite submissions to the EMA and FDA often being based on the same clinical trials.
More drugs were withdrawn by from the market by the FDA (3) compared to the EMA (1). The FDA also approved one-third of medicines before registrational study publication compared with less than 1 in 10 for new EMA oncology approvals.
Oncology therapy development receives the highest proportion of expedited approvals by both the FDA (eg, priority review, fast-track, and accelerated approval) and EMA (eg, accelerated assessment and conditional marketing authorization).
FDA accelerated approval and EMA conditional marketing support earlier approvals of medicines which address unmet medical needs based on surrogate end points that are expected to predict clinical efficacy in later trials.
EMA conditional marketing authorization is valid for 1 year and renewed annually. In comparison, FDA accelerated approval is not subject to annual review but requires completion of confirmatory trials within a specific timeframe, though many are not completed until more than 3 years after initial approval.
While FDA accelerated approval reduces median review by 31 days, EMA conditional marketing authorization increases median review time by 60 days, the authors noted.
Despite both regulators introducing additional programs to further expedite drug development, the median review time for new oncology therapies has increased for both the FDA (by 14 days) and the EMA (74 days) compared with 2003 to 2010.
“The relative concordance in therapies approved by both regulators using expedited pathways suggests similarities in market authorization applications,” the authors wrote. “However, the lower number of new oncology therapies receiving conditional marketing authorization and higher median review times suggests the EMA may have a more cautious approach to use.”
Early approval of therapy may have consequences including uncertainty regarding appropriate use, overall safety and efficacy, and clinical benefit, the authors wrote.
Only 20% of drugs approved with a surrogate end point later showed improvement in overall survival. Previous studies have shown that drugs receiving accelerated approval by the FDA are twice as likely to receive a black box warning indicating serious risk or to be withdrawn from the market.
“The balance between shortening approval times, allowing oncology patients to receive therapies earlier, and ensuring treatments are safe and efficacious is delicate,” they wrote.
The study faced multiple limitations. The analysis was limited to initial approvals in order to compare with previous studies; however, further comparison with supplementary approvals would be informative, the authors wrote. Only official review times were considered, as presubmission enquires or real-time oncology reviews used by both regulators are often confidential, and information is frequently not in the public domain.
Lythgoe MP, Desai A, Gyawali B, et al. Cancer therapy approval timings, review speed, and publication of pivotal registration trials in the US and Europe, 2010-2019. JAMA Netw Open. 2022;5(6):e2216183. doi:10.1001/jamanetworkopen.2022.16183