Evoke Pharma, Inc. – FDA CRL

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for Evoke Pharma, Inc.'s New Drug Application (NDA 209388) for Gimoti (metoclopramide nasal spray). Submitted on May 30, 2018, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, the application was not approved in its current form. The primary deficiencies identified were in Clinical Pharmacology and Product Quality/Device Quality. From a clinical pharmacology perspective, the FDA found the pharmacokinetic bridge between Gimoti and the reference product, Reglan, insufficient. Concerns were raised regarding Gimoti's inconsistent and unreliable delivery of metoclopramide, evidenced by highly variable Cmax levels in some subjects, suggesting very little drug delivery. Regarding product quality, the proposed specification for the drug product was deemed inadequate, particularly the method and acceptance criterion for droplet size distribution. This was linked to the observed clinical variability and potential lack of efficacy, indicating the quality control was not robust enough to ensure consistent drug delivery. To address these issues, Evoke Pharma is required to investigate the root cause of the pharmacokinetic variability and inconsistent drug delivery, providing supporting evidence and mitigation strategies. This may necessitate additional in vitro and/or in vivo studies. For product quality, all proposed tests and acceptance criteria, including droplet sizes and other essential performance characteristics, must be supported by data from three commercial-scale batches manufactured at the proposed commercial site using the commercial formulation and device. The FDA also provided additional recommendations on actuation force, cap removal force, shelf-life data, and a comprehensive safety update for resubmission.