Belzutifan Achieves 98% Disease Control Rate in VHL-Associated Renal Cell Carcinoma, Leveraging Nobel Prize-Winning HIF-2α Pathway

Recently, the phase 2 clinical trial results of belzutifan, a hypoxia-inducible factor inhibitor developed by MSD, for the treatment of patients with renal cell carcinoma associated with von Hippel-Lindau (VHL) disease, were published in The New England Journal of Medicine. The trial results showed that belzutifan achieved a 98% disease control rate, and at 24 months post-treatment, the progression-free survival rate was 96%.

VHL is a rare genetic disease that can abnormally activate hypoxia-inducible factor (HIF-2α) in cancer patients. The HIF-2α factor then accumulates in the patient's body, leading to the formation of benign and malignant tumors. Belzutifan is a potent, selective, novel oral HIF-2α inhibitor. Research related to the HIF-2α pathway won the Nobel Prize in Physiology or Medicine in 2019. Based on the positive interim results of belzutifan in this clinical trial, the U.S. FDA approved it for marketing in August this year.

Results published in The New England Journal of Medicine showed that among 61 patients with renal cell carcinoma who received treatment, 30 (49%) achieved partial response, and another 30 patients (49%) had stable disease. Reduction in tumor lesions was observed in 92% of the patients. At 24 months, the progression-free survival rate was 95%. As of the data cutoff date, 89% of the patients were still receiving treatment.

▲Phase 2 Clinical Trial Data of Belzutifan (Image Source: Reference [1])

Among the 61 patients participating in the trial, lesions were also present in other parts of the body. Belzutifan achieved a 77% objective response rate in reducing pancreatic lesions, including a 10% complete response rate.

Researchers noted in the discussion that the usual treatment for tumors associated with VHL disease is surgery to reduce the risk of metastatic disease. However, since patients with VHL disease face a continuously elevated risk of tumor development in affected organs, most require multiple surgeries over their lifetime.

Note: The original text has been abridged.

References:

[1] Jonasch et al., (2021). Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease. NEJM, DOI: 10.1056/NEJMoa2103425

▽Follow 【WuXi AppTecGermany】WeChat Official Account