Hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor MK-6482, a novel breakthrough therapy discovered by Merck for the treatment of patients with von Hippel-Lindau (VHL) disease-associated Renal Cell Carcinoma (RCC).
MK-6482 (formerly PT2977) an investigational, novel, potent, selective, oral HIF-2α inhibitor which is currently being evaluated in a Phase 3 trial in advanced RCC (NCT04195750), a Phase 2 trial in VHL-associated RCC (NCT03401788), and a Phase 1/2 dose-escalation and dose-expansion trial in advanced solid tumours, including advanced RCC (NCT02974738).Proteins known as hypoxia-inducible factors, including HIF-2α, can accumulate in patients when VHL, a tumour-suppressor protein, is inactivated. The accumulation of HIF-2α can lead to the formation of both benign and malignant tumours.
This breakthrough designation supports the potential of targeting HIF-2α with von Hippel-Lindau disease in patients who have limited treatment options and face an increased risk for benign tumours as well as several types of cancer, including renal cell carcinoma.
U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to MK-6482 for the treatment of patients with von Hippel-Lindau (VHL) disease-associated Renal Cell Carcinoma (RCC)with nonmetastatic RCC tumours less than three centimeters in size, unless immediate surgery is required.
Von Hippel-Lindau disease is a rare genetic disease affecting one in 36,000 people (200,000 cases worldwide and 10,000 cases in the US alone).People affected with VHL disease possess high risk for benign blood vessel tumours as well as several cancers, including RCC. 60% of people suffering with VHL disease develop RCC, which is a leading cause of death for patients with VHL disease. In addition, common type of kidney cancer known as renal cell carcinoma are affecting people in which about nine of 10 kidney cancers are RCCs, and about seven of 10 RCCs are clear cell. In US alone, approximately there are 74,000 new cases of kidney cancer diagnosed and almost 15,000 deaths from the disease in 2020.
