Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we have a quick update on another recent FDA cancer drug approval.
On August 13, 2021, FDA approved belzutifan (brand name Welireg), a hypoxia-inducible factor inhibitor for adult patients with von Hippel-Lindau disease who require therapy for associated renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery.
Belzutifan was investigated in an ongoing, open-label clinical trial in 61 patients with von Hippel-Lindau-associated renal cell carcinoma diagnosed based on a von Hippel-Lindau germline alteration and with at least one measurable solid tumor localized to the kidney. Enrolled patients had other von Hippel-Lindau -associated tumors, including central nervous system hemangioblastomas and pancreatic neuroendocrine tumors.
The primary efficacy endpoint was overall response rate measured by radiology assessment, as assessed by an independent review committee using RECIST v1.1. Additional efficacy endpoints included duration of response, and time- to- response. An overall response rate of 49% was reported in patients with von Hippel-Lindau -associated renal cell carcinoma. All patients with von Hippel-Lindau- renal cell carcinoma with a response were followed for a minimum of 18 months from the start of treatment. The median duration of response was not reached; 56% of responders had duration of response of more than 12 months and a median time- to- response of 8 months. In patients with other von Hippel-Lindau-associated non- renal cell carcinoma tumors, 24 patients with measurable central nervous system hemangioblastomas had an overall response rate of 63% and 12 patients with measurable pancreatic neuroendocrine tumors had an overall response rate of 83%. Median duration of response was not reached, with 73% and 50% of patients having response durations for more than 12 months for central nervous system hemangioblastomas and pancreatic neuroendocrine tumors, respectively.
The most common adverse reactions, including laboratory abnormalities, reported in more than 20% of patients who received belzutifan were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. Anemia and hypoxia from belzutifan use can be severe. In the ongoing study, anemia occurred in 90% of patients and 7% had Grade 3 anemia. Patients should be transfused as clinically indicated. The use of erythropoiesis stimulating agents for treatment of anemia is not recommended in patients treated with belzutifan. In the ongoing study, hypoxia occurred in 1.6% of patients. Belzutifan can render some hormonal contraceptives ineffective, and belzutifan exposure during pregnancy can cause embryo-fetal harm.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, as well as the Assessment Aid and the Product Quality Assessment Aid, voluntary submissions from the applicant to facilitate the FDA’s assessment. The FDA approved this application approximately 1 month ahead of the FDA goal date.
Full prescribing information for this approval can be found on the web at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program.
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