Officials with the FDA have approved the hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor belzutifan (Welireg, Merck) for the treatment of patients with some types of Von Hippel-Lindau (VHL) disease-associated tumors.
The drug has been approved for adults with VHL disease who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgery. It is the first HIF-2α inhibitor therapy approved in the United States, according to a press release from Merck.
VHL disease is estimated to occur in 1 of every 36,000 individuals. Patients with the disease are at risk for benign blood vessel tumors as well as some cancerous ones, such as RCC.
“VHL disease is a rare and serious condition,” said Eric Jonasch, MD, principal investigator of Study 004 and a professor at the University of Texas MD Anderson Cancer Center, in the press release. “Until today, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors.”
The approval was based on data from Study 004, an open-label trial of 61 patients with VHL-associated RCC and at least 1 measurable solid tumor localized to the kidney. Enrolled patients had other VHL-associated tumors and the study excluded patients with metastatic disease. Participants received belzutifan 120 mg once daily until progression of disease or unacceptable toxicity.
According to the press release, the median duration of exposure to belzutifan was 68 weeks. In patients with VHL-associated RCC, belzutifan recipients had an overall response rate (ORR) of 49% and all responses were partial responses. The median duration of response had not yet been reached and among responders, 56% were still responding after at least 12 months. The median time to response was 8 months.
In patients with VHL-associated pancreatic neuroendocrine tumors, belzutifan showed an ORR of 83%, with a complete response rate of 17% and a partial response rate of 67%. The median duration of response had not yet been reached and among responders, 50% were still responding after at least 12 months. The median time to response was 8 months.
“Welireg is the first and only approved systemic therapy for patients with certain types of VHL-associated tumors, representing an important new treatment option for patients affected by this rare condition,” said Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, in the press release.
Serious adverse events (AEs) occurred in 15% of patients who received belzutifan and included anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion. Permanent discontinuation due to AEs occurred in 3.3% of patients and included dizziness and opioid overdose.
Furthermore, dosage interruptions due to an AE occurred in 39% of patients and included fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness. Dose reductions due to an AE occurred in 13% of patients and the most frequent reaction that required dose reduction was fatigue.
Finally, the most common AEs occurring in 25% or more of patients were hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).
“The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors,” said Ramaprasad Srinivasan, MD, PhD, head of the molecular cancer therapeutics section of the Urologic Oncology Branch at the National Cancer Institute, in the press release. “The FDA’s approval of Welireg marks an important step forward by introducing a systemic therapy that has the potential to improve the current treatment paradigm for patients with certain types of VHL-associated tumors.”