FDA CRL - Akeso Biopharma Co., Ltd.

The FDA issued a Complete Response Letter (CRL) to Akeso Biopharma Co., Ltd. regarding its Biologics License Application (BLA 761258) for penpulimab-kcqx (AK105), indicating the application cannot be approved in its present form. Key issues were identified across clinical, product quality, and manufacturing facility compliance following a pre-license inspection (PLI) at Akeso's facility in Zhongshan, China.

Clinically, the FDA determined that results from Study AK105-202 for metastatic nasopharyngeal carcinoma (NPC) did not demonstrate a meaningful advantage over currently available therapies, failing to meet accelerated approval criteria under 21 CFR 601.41. The agency recommends a new multiregional randomized clinical trial with progression-free and overall survival endpoints, ensuring diverse U.S. patient representation, including adolescents.

Product quality deficiencies, cited under 21 CFR 601.20(c), included the lack of a qualified cell bank for sustained commercial supply, inadequate quality control methods, and insufficient data to support drug product manufacturing process control ranges. Akeso must provide extensive data for cell bank qualification, optimize and validate QC methods, and substantiate process control ranges.

Unresolved deficiencies from the PLI at the manufacturing facility also require satisfactory responses, with a potential for re-inspection. Additionally, a comprehensive safety update and specific labeling revisions, including adding a Medication Guide statement per 21 CFR 208.24(d), are required.