FDA CRL - Bioprojet Pharma

The FDA issued a Complete Response Letter (CRL) to Bioprojet Pharma, c/o Harmony Biosciences, LLC, for New Drug Application (NDA) 211150/Original 2, concerning Wakix (pitolisant) tablets for treating cataplexy in adult narcolepsy patients. The application, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act, was not approved due to a lack of substantial evidence of effectiveness.

The primary issues stemmed from the clinical trials. The HARMONY I study was deemed inadequate because cataplexy was a secondary endpoint without proper statistical control, the patient subgroup was defined post-hoc, and statistical significance was dependent on specific handling of missing data. While HARMONY CTP showed positive results, it was considered insufficient on its own due to its small size (105 subjects), exclusive conduct in Eastern Europe, and concerns about generalizability to the U.S. population.

To address these deficiencies, the FDA requires a second, randomized, double-blind, placebo-controlled, fixed-dose trial for cataplexy that includes a meaningful proportion of U.S. patients to substantiate the HARMONY CTP results. Furthermore, Bioprojet Pharma must submit a comprehensive safety update, as detailed in 21 CFR 314.50(d)(5)(vi)(b), and provide updated labeling content in Structured Product Labeling (SPL) format once other issues are resolved. The FDA has offered to provide additional guidance on the required study.