FDA approves Merck's new drug Belzutifan

1.Basic information

Drug name: belzutifan

CAS:1672668-24-4

Target: 9 nM (HIF-2α) (hypoxia inducible factor-2α)

Indications: von Hippel-Lindau disease (Hippel-Lindau syndrome) under certain conditions

Development company: Merck & Co

Approval date: August 13, 2021

2.Clinical

VHL syndrome is a rare genetic disease, one in 36,000 people suffers from this disease (200,000 cases worldwide, 10,000 cases in the United States alone). Patients with VHL syndrome are at risk of developing benign vascular tumors and a variety of cancers including RCC. RCC occurs in up to 70% of patients with VHL syndrome, which is the main cause of death in patients with VHL syndrome. VHL gene is an important tumor suppressor gene, and its mutation was first discovered in patients with VHL syndrome. VHL protein is a tumor suppressor protein, and its inactivation can abnormally activate the hypoxia-inducible factor-2α (HIF-2α) protein in tumor patients. This inactivation of VHL tumor suppressor protein is observed in more than 90% of ccRCC tumors, causing the accumulation and activation of hypoxia-inducible factor (HIF) protein in cancer cells, falsely sending hypoxia signals, which activates blood vessels Form and stimulate the growth of benign and malignant tumors.

A total of 61 patients with VHL disease were enrolled in the Phase 2 clinical trial to evaluate the efficacy of Belzutifan. The primary endpoint is the objective response rate of patients with renal cancer related to VHL disease.

The results showed that among patients with kidney cancer associated with VHL disease, the Belzutifan treatment group achieved a confirmed total remission rate of 36.1%. Other results published at the 2021 Urogenital Cancer Symposium showed that 36.1% of patients had a partial response to Belzutifan, 62.3% of patients were in stable condition, and the median DOR had not yet been reached. At week 52, the PFS of the Belzutifan treatment group was as high as 98.3%. Moreover, 91.8% of patients were treated with HIF-2α inhibitors, the scope of clear cell RCC lesions was reduced. In addition, the study also evaluated the efficacy of other common VHL disease-related tumors, including pancreatic neuroendocrine tumors, central nervous system (CNS) hemangioblastoma, and so on.

3.Preparation Synthesis