OBJECTIVES: Establishing a relevant balance between drug safety and efficacy in patients with malignant disease is considered one of the most challenging decisions that country regulators will have to make for cancer therapy approvals. When decisions about the same anticancer drug application for marketing approval are made differently, questions are raised regarding the reasons why and this creates confusion at the level of both health professionals and society. The objective of this study is to provide a comprehensive and comparative analysis of immune checkpoint inhibitors, particularly PD-1, PDL-1 and CTLA-4, approved by the U.S. Food and Drug Administration (FDA), The European Medicines Agency (EMA) and Health Canada (HC).

METHODS: In the period from 2011 to 2017, a list of all CTLA-4, PDL-1 and PD-1 inhibitors approved by all agencies were gathered. For each drug, the following data were extracted: indications, contraindications, dosage forms, routes of administration, strengths, market statuses, and review statuses. Differences were identified and compared qualitatively and quantitatively.

RESULTS: Out of all immune checkpoint inhibitors, 4 were approved by the three agencies. The average number of approved indications by EMA (3.5±2.06) was higher than FDA (3±1.73) and HC (2±0.7). No differences were found in the dosage forms, strengths and route of administration. HC approved more contraindications (1.25±0.43) than EMA and FDA. Moreover, the qualitative analysis revealed differences in the approved indications in the 4 immune checkpoint inhibitors included in the study. Additionally, differences were identified in the approval dates between the three agencies.

CONCLUSIONS: There are differences in the immune checkpoint inhibitors approved by all regulatory agencies. Furthermore, differences in indications, contraindications, and other characteristics of drugs were identified. Additional efforts on harmonizing the regulatory systems on the decision-making process are needed and may help decrease these differences.