FDA Approves First HIF-2α Inhibitor Therapy in US

Merck (known as MSD outside the United States and Canada) announced in an August 13, 2021 press release that FDA approved Welireg for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery. Welireg is an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor and the first HIF-2α inhibitor therapy approved in the United States. It reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis, and tumor growth. The recommended dose of Welireg is 120 mg once daily until disease progression or unacceptance toxicity.

FDA approval is based on results from the study 004 trial (NCT03401788), an open-label trial in 61 patients with VHL-associated RCC diagnosed based on a VHL germline alteration and with at least one measurable solid tumor localized to the kidney.

“The approval of WELIREG, which is based on data showing an overall response rate across three different types of VHL-associated tumors, addresses this significant unmet need by introducing a new option for physicians and their patients impacted by this disease,” said Eric Jonasch, principal investigator of study 004 and professor, department of Genitourinary medical oncology, division of cancer medicine, The University of Texas MD Anderson Cancer Center, in a press release.