Merck Receives FDA Breakthrough Therapy Designation for HIF-2α Inhibitor MK-6482 in Von Hippel-Lindau Disease-Associated Renal Cell Carcinoma

Today, MSD announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to its hypoxia-inducible factor-2α (HIF-2α) inhibitor, MK-6482, for the treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) who have non-metastatic RCC tumors smaller than 3 cm. The FDA also granted Orphan Drug Designation to MK-6482 for the treatment of VHL disease. These designations are based on data from a Phase 2 trial evaluating MK-6482 in patients with VHL-associated clear cell RCC, which were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. The trial data demonstrated an overall response rate of 27.9% in patients with VHL-associated clear cell RCC, with 86.9% of patients experiencing reduction in target lesions.

Von Hippel-Lindau disease is a rare genetic disorder with an incidence of 1 in 36,000 (approximately 200,000 cases worldwide). Patients with VHL disease are at risk of developing benign vascular tumors and several types of cancer, including renal cell carcinoma (RCC). Up to 60% of patients with VHL disease develop RCC, which is the leading cause of death in this population.

Renal cell carcinoma (RCC) is by far the most common type of kidney cancer; approximately 9 out of 10 kidney cancers are RCC, and about 7 out of 10 RCC cases are clear cell carcinoma. It is estimated that in 2018, approximately 403,000 patients worldwide were diagnosed with kidney cancer, and about 175,000 died from the disease.

MK-6482 (formerly PT2977) is a potent, selective, oral HIF-2α inhibitor currently being evaluated in multiple clinical trials for the treatment of VHL-associated renal cell carcinoma (RCC), advanced RCC, and advanced solid tumors. When the von Hippel-Lindau (VHL) protein, a tumor suppressor, is inactivated, HIF-2α accumulates in patients. The accumulation of HIF-2α can lead to the formation of both benign and malignant tumors. VHL inactivation is observed in more than 90% of clear cell RCC tumors. The biological research on VHL that led to the discovery of HIF-2α was awarded the Nobel Prize in Physiology or Medicine in 2019.

“MSD’s diverse oncology pipeline is focused on delivering innovative therapies to patients with unmet medical needs,” said Dr. Scot Ebbinghaus, Vice President of Clinical Research at MSD Laboratories. “The designation granted to MK-6482 underscores the potential of targeting HIF-2α in certain patients with von Hippel-Lindau (VHL) disease, who currently have limited treatment options and face an increased risk of benign tumors as well as several types of cancer, including renal cell carcinoma.”

References:

[1] FDA Grants Breakthrough Therapy Designation to Merck’s Novel HIF-2α Inhibitor MK-6482 for Treatment of Certain Patients With Von Hippel-Lindau Disease- Associated Renal Cell Carcinoma. Retrieved July 29, 2020, from https://www.businesswire.com/news/home/20200729005246/en

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