Over the last decade, the US FDA is faster to approve new oncology therapies compared with the European EMA; but that speed may have consequences.

A new collaborative study, led by Imperial's Dr Mark Lythgoe and published in JAMA Network, provides insights into regulatory processes for cancer drug approvals between the two largest medical regulators in the world—the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA)

"Faster approval times, and the number of approvals, should only be celebrated if they deliver meaningful outcomes, making patients live better and for longer." Dr Mark Lythgoe Department of Surgery & Cancer

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. 

It was found that 95% of 89 new oncology therapies approved by both regulators, were approved in the United States before receiving European market authorization. With the median review times for the FDA (200 days) being more than half that of the EMA (426 days).

Several reasons have been proposed for the significant difference in approval times:

1) EMA typically received new drug applications after these have been submitted to the FDA.

2) European approval, unlike US approval, is a 2-step process requiring both approval by the Committee for Medicinal Products for Human Use and then European Commission's adoption for centralized approval, with the study identifying a 62-day delay between these steps

3) The FDA also has more expedited review pathways (e.g. priority review, breakthrough designation, fast track, etc.), helping facilitate faster review speed and granting earlier oncology drug approvals than the EMA.  

The speed of drug approval times, as well as the number of FDA-approved cancer medicines, has long been used as a metric for successful regulatory processes. But do quicker approval times correlate to drug success and better outcomes for patients?

The study showed that 19 of 31 oncology drugs (61%) that received accelerated approval from FDA went on to receive regular approval. Three (16%) were withdrawn and nine (27%) currently have accelerated approval status with confirmatory trial results pending. Compared with the EMA's 23 oncology drugs that received conditional marketing authorisation, 10 (43%) received regular approval, one (4%) was withdrawn, and 12 still have conditional marketing authorization status with confirmatory trial results pending.

This work was a collaboration with Mayo Clinic, Vanderbilt University, Queens University and Stanford University with senior author Dr Ali Khaki

Speaking about the findings, Dr Mark Lythgoe from the Department of Surgery and Cancer, said: "Our data shows that a higher number of new oncology drugs are withdrawn by the FDA compared to the EMA, and faster review and/or earlier approval may be a significant factor in this."

The study shows that the speed of FDA review times and the subsequent number of approvals have increased over time, but the proportion of cancer drugs that improve survival appears to have declined. A separate paper in JAMA Internal Medicine had similar findings, showing that of 93 cancer drugs granted FDA accelerated approval between 1992-2017, only 19 (20%) showed an improvement in overall survival.

Dr Lythgoe notes: "Faster approval times, and the number of approvals, should only be celebrated if they deliver meaningful outcomes, making patients live better and for longer."

Speaking about the results of the study and future work, co-author Dr Jon Krell from the Department of Surgery and Cancer, said: "During this study, the UK was part of the EU and EMA, however now as an independent nation it will be interesting to see how approval speed changes at the MHRA, particularly with closer alignment with the FDA through Project Orbis for new cancer medicines."

Cancer therapy approval timings, review speed, and publication of pivotal registration trials in the US and Europe, 2010-2019. Lythgoe MP, Desai A, Gyawali B, et al. JAMA Network Open. 2022;5(6):e2216183. doi:10.1001/jamanetworkopen.2022.16183 

Some information in this article was taken from an invited commentary on the study, published 10 June in JAMA Network Open.