FDA CRL - Takeda Pharmaceuticals U.S.A., Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Takeda Pharmaceuticals U.S.A., Inc. regarding its New Drug Application (NDA 213976) for Eohilia (budesonide oral suspension) for eosinophilic esophagitis (EoE), submitted October 15, 2020. The FDA determined that the application, filed under section 505(b)(2) and holding a breakthrough therapy designation, lacked substantial evidence of effectiveness, preventing its approval.Key deficiencies included the symptomatic co-primary endpoint in a pivotal trial (SHP621-301) not demonstrating clinically meaningful change, and the histologic response lacking sustained benefit in a long-term trial (SHP621-302). The FDA consistently emphasized the need for robust long-term efficacy data, which the submitted phase 3 trial failed to establish. Furthermore, post-hoc subgroup analyses of patients without prior dilation were deemed unreliable due to insufficient documentation.To resolve these issues, the FDA recommends Takeda conduct a new, adequate and well-controlled study. This study should include prespecified subpopulations (e.g., dilation-naive patients with confirmed medical records or those with more severe baseline symptoms), assessing symptomatic and histologic co-primary endpoints over at least a 24-week treatment period, followed by an extension totaling at least 52 weeks for safety and durability. The company must propose a clinically meaningful change for symptomatic endpoints, and this new study must be completed before resubmission.