FDA CRL - NeuroDerm, Ltd.

NeuroDerm, Ltd. received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA 218317) for Engolce (carbidopa and levodopa) injection. The FDA declined approval due to several outstanding issues. A significant concern was an inadequate scientific bridge for carbidopa pharmacokinetic (PK) exposure. Engolce's carbidopa exposure was substantially higher than the reference drug, Sinemet, preventing the FDA from relying on Sinemet's established safety profile for carbidopa. As a result, NeuroDerm must conduct a thorough QT (TQT) study to assess Engolce's potential effects on the QTc interval, considering the elevated carbidopa exposure, which could be further increased if patients use other carbidopa/levodopa products. Furthermore, pre-approval inspections of two facilities identified deficiencies, requiring satisfactory responses to the FDA. The company is also mandated to resubmit the proposed proprietary name once other deficiencies are resolved. A comprehensive safety update is required, including new nonclinical and clinical safety data, revised adverse event tabulations, updated exposure information, and a summary of worldwide safety experience. NeuroDerm must also address potential drug-drug interactions stemming from higher carbidopa exposure and provide clear labeling instructions for converting patients from other oral carbidopa/levodopa products to Engolce.