Merck Fortifies Oncology Pipeline with FDA Win for HIF-2α Inhibitor, Welireg

Von Hippel-Lindau (VHL) syndrome is a rare and serious condition characterized by the formation of cancerous or noncancerous tumors and fluid-filled sacs (cysts) in different parts of the body. VHL-related tumors include hemangioblastomas (blood vessel tumors of the brain, spinal cord, and retina), renal cell carcinoma, and pancreatic neuroendocrine tumor (pNET).

On August 13th, Merck (known as MSD outside the United States and Canada) announced the FDA approval of its hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, Welireg (belzutifan) for adult patients with VHL disease-associated tumors. The approval is based on positive outcomes from Study 004, which evaluated the drug.

“Welireg’s approval in VHL-disease associated tumors addresses the significant unmet need by introducing a new option for physicians and their patients impacted by this disease,” said principal investigator Dr. Eric Jonasch from The University of Texas MD Anderson Cancer Center.

First and Only Approval

VHL disease affects 1 in 36,000 people with an estimated incidence of 10,000 patients in the U.S. Surgery, including minimally invasive and laser surgery in some cases, is the primary treatment for VHL-associated problems. However, there were no systemic therapies approved to treat VHL patients.

Welireg is the first and only approved systemic therapy in the US for treating patients impacted by this rare genetic disorder. Welireg’s approval is based on efficacy data from the open-label Study 004 trial in patients with VHL-associated tumors.

According to Dr. Scot Ebbinghaus, Vice President, clinical research, Merck Research Laboratories, “Welireg’s approval is a significant milestone and is a testament to Merck’s commitment to bring forward innovative new treatment options for more patients, thus expanding Merck’s oncology portfolio.”

Positive Outcomes from Study 004

Welireg was evaluated in Study 004 (NCT03401788), which enrolled 61 patients with VHL-associated RCC with at least one measurable solid tumor. The patients had other VHL-associated tumors, including CNS hemangioblastomas and pNET.

Patients received 120mg of Welireg once daily until the progression of the disease or unacceptable toxicity, with a median exposure of 68 weeks. Results show that Welireg showed a reduction of tumors in nearly half of all patients with VHL-associated RCC and in a majority of patients with other tumors.

“The FDA’s approval of Welireg marks an important step by introducing a non-surgical treatment option improving the current paradigm for patients with VHL-associated tumors,” said Dr. Ramaprasad Srinivasan, head, Molecular Cancer Therapeutics Section, Urologic Oncology Branch, NCI, and principal investigator on CRADA.

Merck got hold of Welireg from its $2.2 billion acquisition of Peloton Therapeutics in 2019. This approval will give the necessary fillip to its oncology sales and help reduce the dependency on its blockbuster drug, Keytruda.

The pharma giant is now working to optimize the production of Welireg to allow for a sustainable supply to meet anticipated US demand. Commercial supply is expected to be available by early September, the company said in a statement.

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Manju Bhaskar