Complete Response Letter NDA 505b1 220049 (Aug 18, 2025)
The FDA has issued a Complete Response Letter (CRL) for NDA 220049 for vatiquinone, indicating that the application is not ready for approval in its current form. The agency found that the nominally significant findings on exploratory endpoints (Upright Stability Subscale and Modified Fatigue Impact Scale) were not statistically robust or persuasive enough to establish effectiveness, especially given negative results on primary and key secondary endpoints. Concerns were raised regarding statistical observations, handling of missing data, baseline imbalances, and the interpretability of certain outcome assessments. Real-world evidence and biomarker data submitted as confirmatory evidence were deemed insufficient to serve as such without a positive, adequate, and well-controlled study. The FDA requires a new positive, adequate, and well-controlled study to establish effectiveness, suggests a specific study design, and outlines deficiencies related to nonclinical/product quality, labeling, proprietary name, and a comprehensive safety update for any resubmission.
