FDA skepticism challenges sintilimab’s approval for NSCLC, citing concerns over trial data exclusivity from China and its less favored endpoint of PFS.

The FDA appears skeptical about approving sintilimab, an investigational checkpoint inhibitor for non-small cell lung cancer (NSCLC), based on briefing documents released ahead of an advisory committee meeting. The concerns stem from the data being exclusively from a Chinese clinical trial and the use of progression-free survival (PFS) as the primary endpoint, which FDA staff considers a “lesser endpoint” compared to overall survival improvements used for current first-line immunotherapy approvals in the U.S. The market for PD-1/L1 inhibitors is already crowded, and FDA staff question the applicability of the trial results to the diverse U.S. population.

Innovent Biologics and Eli Lilly’s ORIENT-11 phase III trial of sintilimab, conducted solely in China, showed that the drug improved median PFS to 8.9 months versus 5.0 months with placebo. Other measures such as objective response rate and disease control rate also favored sintilimab, and the safety profile was deemed acceptable. However, FDA staff argue that sintilimab does not offer significant safety or administration advantages over existing treatments for the U.S. patient population.

FDA staff expressed concerns about the generalizability of the ORIENT-11 trial’s findings to the American demographic due to its lack of racial and ethnic diversity. They also noted the trial’s departure from current guidelines promoting harmonized drug development through multi-regional clinical trials. The FDA’s critical stance suggests a challenging path for sintilimab’s approval in the U.S. for NSCLC treatment.