FDA CRL - Ultragenyx Pharmaceutical Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Ultragenyx Pharmaceutical Inc. on July 7, 2025, regarding their Biologics License Application (BLA) for rebisufligene etisparvovec. The FDA's Center for Biologics Evaluation and Research (CBER) concluded that final approval could not be granted due to significant deficiencies in Chemistry, Manufacturing, and Controls (CMC) and outstanding clinical data requirements. CBER conducted pre-license inspections of Ultragenyx and other facilities, resulting in Form FDA 483 observations. Ultragenyx's responses were deemed insufficient, as corrective actions were not comprehensive enough to address systemic issues. Consequently, CBER could not determine that the product and establishment comply with BLA standards and Current Good Manufacturing Practice (CGMP) requirements, as per 21 CFR 601.20(a) and (d). These issues require additional review and verification via follow-up inspections. Clinically, the FDA is evaluating the adequacy of existing data and requires updated safety and efficacy information with any resubmission. This includes specific raw scores from developmental assessments (Bayley Scales of Infant and Toddler Development-Third Edition, Vineland Adaptive Behavioral Scales-Second Edition), brain MRI results, and cerebrospinal fluid biomarkers from all treated patients, updated to 30 days prior to resubmission. Ultragenyx must fully address all identified deficiencies, providing a comprehensive response within one year to either resubmit the application or withdraw it. A partial response will not be processed. The company may request meetings with the FDA to discuss the necessary steps for approval.