Immune checkpoint inhibitors for the treatment of non-small cell lung cancer: A comparison of the regulatory approvals in Europe and the United States

Abstract

Regulatory authorization of oncology drugs, including immune-checkpoint inhibitors, is often based on enhanced efficacy and acceptable toxicity profiles, investigated in randomized, open-label clinical trials. Regulatory approval decisions of the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are frequently compared and contrasted, specifically based on review requirements, and time to approval or refusal decisions. We reviewed databases of the US FDA, the EMA and Clinicaltrials.gov, from January 1, 2015 until December 31, 2021, and analyzed regulatory approvals for immune-checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC). We specifically focused on time to approval duration of each immune-checkpoint inhibitor, and considerations of patient-reported outcomes (PROs) by each regulatory agency. Despite similarities in the regulatory pathways and methods used for immune-checkpoint inhibitor approvals, NSCLC indications that stood out in terms of outcome divergence were mainly first-line drugs for treatment naïve patients. The US FDA was quicker to reach approval decisions, when compared with the EMA. The US FDA and the EMA both recognize the value of PROs as important patient-centered endpoints. Policy statement: There are several regulatory structures in the US and Europe that aim to leverage the latest clinical trial evidence and speed up the regulatory approval processes. In our study, the preponderance of outcome differences in approvals were not influenced by the expedited drug development and access programs. Increased harmonization and collaboration on the PRO measurement and validation are encouraged among these agencies to improve the efficiency of regulatory decisions in the future.