FDA Approval Summary: Belzutifan for VHL Disease Tumors-Response.

Belzutifan received FDA approval for VHL-associated disease including central nervous system hemangioblastomas (CNS HB) in August 2021. The approval was based on results of the single-arm MK-6482 study that included 61 patients overall treated with belzutifan 120 mg orally daily, including 51 with CNS HB at baseline (per investigator assessment). The overall response rate for CNS HB in MK-6482-004 was 63% in 24 patients who had CNS HB with a measurable solid lesion with a median time to response of 3.1 months (range: 2.5–11; refs. 1, 2).Trinh and colleagues reported that a 54-year-old man with VHL disease developed bleeding in a previously undiagnosed hemangioblastoma in his spine 4 days after initiation of treatment with belzutifan (3). Intracranial hemorrhage is a known, but rare, serious complication of VHL disease–associated CNS HB (4). The package insert for belzutifan currently does not identify hemorrhage, including CNS hemorrhage, as an adverse reaction observed in patients receiving belzutifan in the setting of clinical trials.FDA review of the safety and efficacy of drugs does not end at marketing approval and the FDA continues to assess these in the postmarketing setting. The FDA Adverse Event Reporting System (FAERS) is a database that contains information on postmarketing adverse event, and medication error reports and product quality complaints resulting in adverse events. The database is designed to support the FDA's postmarketing safety surveillance program for drug and therapeutic biologic products (5). Health care professionals are encouraged to report the adverse events they observe with belzutifan and any other drug to the FDA via the FAERS database unless the adverse events are clearly due to disease progression or extraneous causes. FDA continually reassesses safety information and benefit-risk profile for approved drugs as more data are collected both from clinical trials and from the postmarketing setting to ensure safe and effective use. FDA encourages clinicians and patients to regularly refer to updated product labeling and Patient Package Insert for full information about safe and effective product use.See the original Letter to the Editor, p. 684No disclosures were reported.