Immune checkpoint inhibitors (ICI): An analysis of FDA’s and EMA’s decision patterns and times for initial approvals and extensions of indication.

Abstract

e14062 Background: In certain clinical settings ICI have demonstrated unprecedented patterns of efficacy, resulting since 2011 in regulatory approvals worldwide in a variety of cancer indications. As immuno-oncology (IO) drugs constitute today an intense area of oncology drug development, we sought to analyze and compare the regulatory approval decisions for ICI, issued until end of 2018 by the US FDA and the European Medicines Agency (EMA). Methods: We reviewed the biological license applications (BLA) of the 7 (EU: 6) ICI, for which marketing approval decisions for were granted so far. Together with parallel and extension of indication applications, 43 (FDA) respectively 23 (EMA) approval procedures were finalized between March 2011 and December 2018. We analyzed agency decision outcomes and timeline patterns; approval decisions issued for novel non-IO cancer drugs served as benchmarks. The primary variable for analysis was median approval time (MAT). Results: MAT for initial BLA applications for ICI in the USA were with 189 days [Interquartile range (IQR) 154-209] shorter than MAT for BLA and NDA approvals for non-IO drugs: for the 51 novel oncology drugs approved 2011-2018 by the FDA, MAT was 227 days [IQR 159-303]. With 181 days [IQR 155-184], FDA’s MAT for ICI line extensions did not differ from MAT for initial ICI approvals. For the EU, MAT for initial ICI marketing applications were with 373 days (IQR 326-413) also shorter than MAT for the 51 non-IO drugs approved 2011-18 (422 days [IQR 368-450]); for ICI line extensions, MAT was 254 days [IQR 187-293). Conclusions: For ICI as for novel non-IO cancer drugs, initial regulatory approvals are usually issued in the USA first. Regulatory approval times for initial approvals are shorter in the USA, compared to Europe, the same applies for ICI extensions of indication. FDA’s extensive granting of breakthrough therapy designations (BTD) helped to bring US MAT for initial ICI BLA down to 6 months – i.e. to the same time, FDA requires for its priority review of extensions of indication. For some ICI extensions of indication, the granting of BTD supported approval decisions within 3 months, supporting patients’ rapid access to novel therapies.