Merck Submits Clinical Trial Application in China for Belzutifan, a Novel Therapy Targeting Nobel Prize-Winning HIF-2α Pathway

On February 20, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) announced in its latest public notice that the clinical trial application for belzutifan tablets, a Class 1 new drug submitted by Merck Sharp & Dohme (MSD), has been accepted. Belzutifan (MK-6482) targets a signaling pathway associated with hypoxia-inducible factor-2α (HIF-2α), research on which was awarded the Nobel Prize in Physiology or Medicine in 2019. Based on positive results from clinical trials, the U.S. Food and Drug Administration (FDA) has granted belzutifan Breakthrough Therapy Designation and Orphan Drug Status.

Image source: CDE official website

Belzutifan is an investigational, novel, potent, and selective oral HIF-2α inhibitor currently being evaluated in multiple clinical studies for the treatment of patients with Von Hippel-Lindau (VHL)-associated renal cell carcinoma (RCC), advanced RCC, and advanced solid tumors. Inactivation of the VHL protein, a tumor suppressor, leads to abnormal activation of the HIF-2α protein in cancer patients; accumulation of HIF-2α can result in the formation of both benign and malignant tumors.

According to data from a phase 2 trial evaluating belzutifan in patients with VHL-associated clear cell renal cell carcinoma (RCC), which were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, the study demonstrated an overall response rate of 27.9% in patients with VHL-associated clear cell RCC, with 86.9% of patients experiencing a reduction in target lesions.

Based on these findings, belzutifan received FDA Breakthrough Therapy designation in July 2020 for the treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) who have non-metastatic RCC tumors less than 3 cm in size. The FDA also granted orphan drug designation to this product for the treatment of VHL disease.

Von Hippel-Lindau (VHL) disease is a rare genetic disorder. 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. Clinical study results for belzutifan have demonstrated its potential to target HIF-2α in certain patients with VHL disease who currently have limited treatment options and face an increased risk of multiple types of cancer.

Note: This article aims to introduce advances in pharmaceutical and health research and does not constitute treatment recommendations. For guidance on treatment plans, please consult a qualified medical institution.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Feb 20, 2021, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] 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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