FDA CRL - ORGANON USA INC

Organon, Inc. received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA 21-164) for Gepirone hydrochloride Extended-Release Tablets (20 mg, 40 mg, 60 mg, and 80 mg). The application, resubmitted on May 18, 2001, was deemed inadequate under section 505(d) of the Federal Food, Drug, and Cosmetic Act and 21 CFR 314.125(b), rendering it not approvable.

The primary deficiencies centered on the lack of adequate efficacy data to support a claim in major depressive disorder (MDD) and insufficient long-term safety data. While one ER study was considered positive, the FDA rejected three supporting Immediate-Release (IR) studies. Study 03A7A-003 faced concerns about the patient population's diagnostic criteria, with unusually low baseline depression scores suggesting potential misclassification. Study 03A7C-001-B's positive results were attributed to a single, small center exhibiting an "extremely unusual" lack of placebo effect. Study 03A7A-002 failed to show significant differences on primary efficacy endpoints, and key relapse definitions were identified post-hoc. Additionally, the lack of information on planned interim analyses for the IR studies raised concerns about potential bias.

Organon, Inc. must provide substantial evidence of effectiveness for MDD and adequate long-term safety data to address these critical deficiencies. Clarifications regarding patient selection for Study 03A7A-003 may also be required.