Application of Accelerated Approval to Immunotherapy Drugs

The FDA's Accelerated Approval pathway used surrogate measures that are "reasonably likely" to predict clinical benefit to enable the approval of investigational drugs for urgent medical needs. However, there is limited study to explore the relationship between these surrogate endpoints and patient-centered endpoints. Additionally, few studies have specifically focused on immunotherapies, a rapidly evolving approach in cancer treatment. Therefore, we aim to evaluate the trend and characteristics of immunotherapies receiving accelerated approval (AA) and assess the association between surrogate endpoints and hard endpoints. In this study, we analyzed publicly available FDA data to identify immunotherapies granted Accelerated Approval (AA). We then used linear regression models to examine the relationship between surrogate and hard endpoints. Additionally, a random-effects model was applied to estimate the impact on progression-free survival (PFS) and overall survival (OS). Our study found that the number of immunotherapies granted AA has increased, with approvals restricted to antibodies and immune checkpoint inhibitors (ICIs). On average, the transition from AA to full approval took about four years, with a shorter timeframe observed after 2014. The common surrogate endpoints including overall response rate (ORR) and PFS. When examining the association between surrogate and hard endpoints, neither ORR nor PFS showed a statistically significant correlation with OS. Finally, immunotherapies improved both OS and PFS. However, in a subgroup analysis by cancer type, the 95% confidence interval was near the borderline. In conclusion, there is no direct link between surrogate and hard endpoints, highlighting the need to balance the potential risks of treatments without full FDA approval against the severity of the disease. Most importantly, patients should be fully informed about the potential risks associated with treatments granted AA.