FDA CRL - Vyluma, Inc.

Vyluma, Inc. received a Complete Response Letter from the FDA for its New Drug Application (NDA) 217711 for atropine sulphate ophthalmic solution, 0.01%, intended for pediatric myopia treatment. The FDA cited a lack of substantial evidence of effectiveness, as required by 21 CFR 314.126, noting that the clinical studies, particularly the CHAMP study, did not support the drug's efficacy. Key clinical issues included the CHAMP study's failure to meet its pre-specified hierarchical testing procedure, significant and imbalanced missing data that introduced bias, and flawed statistical analyses of treatment effects. The FDA found that the company's post-hoc analyses could not overcome these fundamental deficiencies. Furthermore, submitted supportive studies were deemed insufficient, either due to short duration or lack of generalizability to the U.S. population, with one U.S. study (MTS1) failing to show efficacy for the 0.01% concentration. Additionally, a facility inspection revealed Current Good Manufacturing Practice (CGMP) deficiencies. To resolve these issues, Vyluma must provide new clinical data demonstrating effectiveness through adequate and well-controlled investigations. The involved manufacturing facility must also satisfactorily address all inspectional deficiencies, ensure CGMP compliance, and may undergo re-inspection and a Pre-Approval Inspection before the application can be reconsidered. Labeling comments are deferred until clinical and manufacturing issues are resolved.