FDA CRL - Pfizer Ireland Pharmaceuticals

The FDA issued a Complete Response Letter (CRL) to Pfizer Ireland Pharmaceuticals for its Biologic License Application (BLA) 761184, concerning MOD-4023 injection. The FDA determined the application could not be approved in its current form due to significant clinical and manufacturing issues.A primary concern was the high rate of anti-drug antibody (ADA) formation (77%) in MOD-4023-treated subjects, compared to the active comparator. This included persistent antibodies and the development of neutralizing antibodies, with one patient experiencing a concerning reduction in height velocity. The FDA cited insufficient data to confirm the long-term impact of immunogenicity on growth or potential interference with other human growth hormone (hGH) therapies, deeming the benefit-risk profile unfavorable given existing alternatives. Pfizer is required to provide data demonstrating that ADA formation does not impact long-term growth or cross-react with other hGH products, and to offer mitigation strategies for neutralizing antibodies.Additionally, critical inspections of Pfizer's manufacturing facilities in Dublin, Ireland, and Belgium could not be completed due to travel restrictions. These inspections are mandatory for assessing compliance with Current Good Manufacturing Practices (CGMP) and are prerequisite for approval.Pfizer must also submit a comprehensive safety update, including all new clinical and nonclinical data, detailed changes in the safety profile, updated adverse event frequencies, and worldwide safety experience. While a proprietary name, Ngenla, was found acceptable, its resubmission is required once all other deficiencies are addressed. Approval is pending resolution of all identified issues and successful facility inspections.