The FDA has approved Merck’s Welireg therapy, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.
An inhibitor of HIF-2α, the therapy reportedly reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumour growth. Exposure to Welireg during pregnancy can cause embryo-fetal harm, and can render hormonal contraceptives ineffective. It can also cause serious anaemia and hypoxia that may require discontinuation or hospitalisation.
“VHL disease is a rare and serious condition. Until today, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors,” said Dr 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. “The approval of Welireg, which is based on data showing an overall response rate across three different types of VHL-associated tumours, addresses this significant unmet need by introducing a new option for physicians and their patients impacted by this disease.”
“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 Dr Scot Ebbinghaus, VP of clinical research, Merck Research Laboratories.
“The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors,” said Dr Ramaprasad Srinivasan, head, Molecular Cancer Therapeutics Section, Urologic Oncology Branch, National Cancer Institute (NCI), and principal investigator on the Cooperative Research and Development Agreement (CRADA) under which the NCI served as a site in Study 004.
“In Study 004, nearly half of all patients with VHL-associated renal cell carcinoma, as well as the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with Welireg experienced a reduction of their respective tumour size. 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 tumours.”
Merck is working to optimise production to allow for a sustainable supply of the therapy to meet anticipated US demand. Commercial supply is expected to be available by early September.