Merck's VHL Drug Becomes First-Ever HIF-2α Inhibitor Approved in U.S.

After FDA approval welireg became the first drug for von Hippel-Lindau. (Chris Hondros/Getty Images)

After FDA approval welireg became the first drug for von Hippel-Lindau. (Chris Hondros/Getty Images)

Merck won U.S. Food and Drug Administration (FDA) approval for a first-of-its-kind oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor that is used to treat a rare genetic disease that causes benign and cancerous tumors in blood vessels associated with renal cell carcinoma.

Merck’s Welireg won FDA approval for adult patients with von Hippel-Lindau disease who require therapy for associated RCC, central nervous system hemangioblastomas or pancreatic neuroendocrine tumors that do not require immediate surgery. The approval marks the first HIF-2α inhibitor therapy approved in the United States. By inhibiting HIF-2α, Welireg reduces the transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumor growth. 

Until the approval of Welireg, the primary treatment for patients with von Hippel-Lindau disease has been surgery.

About the Approval of Welireg

Welireg was approved based on the STUDY 004 trial results, which showed a positive overall response rate (ORR) in patients with VHL-associated RCC. In those patients, Welireg demonstrated an ORR of 49%. All responses were partial responses. 

A median Duration of Response had not yet been met, with patients still responding to the drug after at least 12 months. In patients with VHL-associated CNS hemangioblastomas, Welireg showed an ORR of 63%, including a complete response rate of 4% and a partial response rate of 58%. 

In patients with VHL-associated pNET, Welireg demonstrated an ORR of 83%. That included a complete response rate of 17% and a partial response rate of 67%. Median duration of response had not yet been reached in both of these disease types.

Data showed that nearly half of all patients with VHL-associated renal cell carcinoma, the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with Welireg saw a reduction of their respective tumor size. Scot Ebbinghaus, vice president of clinical research at Merck Research Laboratories, said Welireg is the only approved systemic therapy for patients with certain types of VHL-associated tumors. The approval represents an important new treatment option for patients impacted by this rare disease. 

Eric Jonasch, the principal investigator of STUDY 004 and a professor in the Department of Genitourinary Medical Oncology at MD Anderson, said the approval of Welireg addresses a significant unmet need in this disease by providing a new option for physicians treating their patients. 

Welireg was approved with a black-box warning label. Exposure to the medication during pregnancy can cause embryo-fetal harm.

With approval in hand, Merck said it is working to optimize the production of Welireg to ensure a sustainable supply for demand in the United States. It is estimated that there are about 10,000 people in the country with this disease. The incidence of von Hippel-Lindau disease is estimated to be one in 36,000 individuals. The drug is expected to be available commercially in early September. 

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