FDA CRL - SYDNEXIS Inc.

Sydnexis Inc. received a Complete Response Letter from the FDA regarding its New Drug Application (NDA 219694) for Atropine sulfate ophthalmic solution, 0.01%, intended for the treatment of pediatric myopia. Under the regulatory framework of 21 CFR 314.126, the FDA determined the application lacked substantial evidence of effectiveness. The primary clinical study, SYD-101-001, failed to demonstrate a clinically meaningful benefit; while the 0.01% dose met some statistical endpoints, the actual difference in vision correction compared to the placebo was minimal and diminished over 36 months. The FDA noted that such a small improvement would not justify chronic daily use, as it would not change a child's need for corrective lenses or meaningfully reduce the risk of future retinal complications. Additionally, the FDA raised concerns regarding significant missing data—affecting roughly 26% of participants—which undermined the robustness of the results. The agency also questioned the generalizability of the data to the U.S. population, noting that supportive studies were conducted primarily in Asian populations and did not align with results from non-Asian demographics. Although no inspection-related violations were listed in this clinical review, Sydnexis is required to address these clinical deficiencies in a formal resubmission within one year. This resubmission must include a comprehensive safety update for all related trials and a new request for proprietary name review. The FDA suggested a meeting to discuss the necessary steps for potential approval.