Discrepancies in the therapeutic indications granted by the European Medicines Agency and the US Food and Drug Administration for new cancer drugs: An analysis of potential explanations

Background: Studies have found notable differences between the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in indications granted to new cancer drugs (e.g., different treatment lines). It is unknown why they occur; therefore, we aimed to analyse if maturity of data or characteristics of the pivotal trials might be explanations. 

Methods: New cancer drugs approved by both EMA and the FDA in the study period between January 1, 2020, to December 31, 2022, and new cancer drugs that were approved by one agency in the study period and at the other agency outside the study period were included in the analysis. The drugs were identified by searching the FDA and EMA websites. 

Results: A total of 36 new cancer drugs were included. Notable differences between EMA and the FDA in the granted indication were found in 15 (42 %) of the drugs. The proportion of cancer drugs with differences in maturity of data at time of assessment between EMA and the FDA was similar for drugs with and without notable differences in the indication. Furthermore, the results did not indicate that low level of evidence (e.g., early phase trial as the pivotal, single-arm design, or use of surrogate endpoints) was more common in the cancer drugs with notable differences in the indication. 

Conclusion: The frequent discrepancies in the granted indications between EMA and the FDA for new cancer drugs during a three year period could not be explained by maturity of data at time of assessment or characteristics of the pivotal trials. Therefore, divergence in regulatory policies between the two agencies is considered a more likely explanation. 

Policy summary: Discrepancies between regulatory agencies in the indications granted to new cancer drugs suggest a problematic extrapolation and thus uncertainty regarding the clinical benefit for the patients. The present study seeks to identify potential explanations for the discrepancies to reduce the misalignment in the future.