FDA CRL - HERON THERAPEUTICS, INC.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Heron Therapeutics, Inc. regarding its New Drug Application (NDA 211988) for Zynrelef (bupivacaine and meloxicam) Solution. The application, initially submitted on October 30, 2018, cannot be approved in its current form due to several nonclinical deficiencies.

The main issues center on insufficient data to adequately support the safety profile of excipients and a product specification. For triacetin, the FDA requires data to demonstrate a lack of systemic exposure following wound instillation or new reproductive and developmental toxicology studies. Similarly, for DMSO, Heron must provide a scientific bridge to show that previously referenced oral studies adequately cover exposures from the proposed drug product, or conduct appropriate new studies. The application also lacked data to qualify a proposed drug product specification, necessitating either a local tissue toxicity study at the maximum specified level or a reduction in the specification. Furthermore, for maleic acid, justification is needed to demonstrate that an oral embryofetal development study provides adequate exposure coverage for the instillation route.

To resolve these issues, Heron Therapeutics must provide additional nonclinical data or conduct new studies as outlined. Upon resubmission, a comprehensive safety update, including all new nonclinical and clinical safety data, adverse event summaries, and worldwide experience, is required. The proposed proprietary name, Zynrelef, must also be resubmitted.