MSD – known as Merck & Co in the US and Canada – has received a US Food and Drug Administration (FDA) for its HIF-2α inhibitor Welireg (belzutifan) for the treatment of patients with von Hippel-Lindau (VHL) disease-associated cancers.

Welireg becomes the first approved treatment in the US for adult patients with VHL disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas or pancreatic neuroendocrine tumours (pNET) who do not require immediate surgery.

VHL disease is a rare genetic disease which puts patients at risk of developing benign blood vessel tumours as well as several cancers, including RCC. Up to 70% of people with VHL disease develop RCC.

The HIF-2α inhibitor was investigated in the ongoing Study 004 in 61 patients with VHL-associated RCC, with enrolled patient also having other VHL-associated tumours including CNS hemangioblastomas and pNET.

In this study, an overall response rate of 49% was reported in patients with VHL-associated RCC, with all VHL-RCC patients with a response followed for a minimum of 18 months from the start of treatment.

The median duration of response (DoR) was not reached for these patients, with 56% of responders having DoR ≥ 12 months and a median time-to-response of eight months.

In patients with other VHL-associated non-RCC tumours, 24 patients with measurable CNS hemangioblastomas had an ORR of 63% and 12 patients with measurable pNET had an ORR of 83%.

For these patients, median DoR was not reached, with 73% and 50% of patients having response durations ≥ 12 months for CNS hemangioblastomas and pNET, respectively.

The FDA reviewed Welireg under its Project Orbis initiative, which provides a framework for concurrent submission and review of oncology drugs among international partners.

The Welireg review also utilised the FDA’s ‘Real-Time Oncology Review’ pilot programme, which aims to streamline data submission prior to the filing of the entire clinical application.