Merck’s Welireg Cleared for Rare Tumors

The therapy is expected to be available by early September.

The FDA has approved the first of a new type of medication, an oral inhibitor of a protein involved in a rare genetic disease that leads to cancerous tumors.

Merck’s Welireg (belzutifan), an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, was approved to treat adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors.

VHL effects 1 in 36,000 people, according to the National Organization for Rare Disorders. The mean age of onset of 26 years, and 97% of people with a VHL gene mutation have symptoms by the age of 65.

Until now, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors, Eric Jonasch, M.D., principal investigator of Welireg’s clinical trial and professor in the department of genitourinary medical oncology, division of cancer medicine, at the University of Texas MD Anderson Cancer Center, said in a statement.

“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,” Jonasch said.

As an inhibitor of HIF-2α, Welireg reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis, and tumor growth.

In the cooperative Merck-National Cancer Institute clinical trial, patients with VHL-associated renal cell carcinoma, Welireg demonstrated an overall response rate of 49% and the median time to response was 8 months.

In patients with VHL-associated CNS hemangioblastomas, Welireg showed an overall response rate of 63%, with a complete response rate of 4% and a partial response rate of 58%.

The Welireg label contains a boxed warning that exposure to the drug during pregnancy can cause embryo-fetal harm. Welireg can cause severe anemia that can require a blood transfusion. Welireg can also cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.

Merck executives said in a press release the company is working to optimize production of Welireg “to allow for a sustainable supply to meet anticipated U.S. demand,” and expects it to be available by early September.

The medication’s recommended dose is 120 mg once daily until disease progression.