NMPA Approves Belzutifan for VHL in RCC, CNS Hemangioblastomas, or pNETs

China’s National Medical Products Administration (NMPA) has approved belzutifan (Welireg) for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs), not requiring immediate surgery.¹ This regulatory decision represents the 17th global approval for patients with these diseases.

Objective response rate (ORR) and median duration of response (DOR) data from the phase 2 LITESPARK-004 trial (NCT03401788) supported the NMPA’s decision. The ORR among patients with VHL-associated RCC was 49% (95% CI, 36%-62%); all responses were partial. The median DOR was not yet reached (NR; range, 2.8+ to 22.3+), and 17 of 30 responding patients maintained a response for a minimum of 12 months.

Additional data from LITESPARK-004 demonstrated that patients with VHL-associated CNS hemangioblastomas (n = 24) achieved an ORR of 63% (95% CI, 41%-81%), including a complete response (CR) rate of 4%. The median DOR was NR (range, 3.7+ to 22.3+) with 73% of responders maintaining a response for at least 12 months. The ORR among patients with VHL-associated pNETs (n = 12) was 83% (95% CI, 52%-98%), with a CR rate of 17%. The median DOR was NR (range, 10.8+ to 19.4+), and 50% of responders maintained a response for at least 12 months.

“This approval of belzutifan brings the first and only systemic therapy to adult patients in China with certain VHL disease–associated tumors who, to date, have not had access to a nonsurgical treatment option to help manage manifestations of VHL disease,” Marjorie Green, MD, senior vice president and head of oncology and global clinical development at Merck Research Laboratories, stated in a news release. “We are committed to bringing innovative treatment options to patients in need around the world and are proud to offer eligible adult patients in China a first-in-class HIF-2α inhibitor as a possible treatment option.”

Belzutifan was approved by the FDA in August 2021 for the treatment of adult patients with VHL disease who require therapy for RCC, CNS hemangioblastomas, or pNETs that does not require immediate surgery.² The regulatory decision was also supported by findings from LITESPARK-004.

LITESPARK-004 was a multicenter, open-label, single-arm study that enrolled adult patients with VHL disease-associated RCC and other associated neoplasms in the United States, Denmark, France, and the United Kingdom.³ Eligible patients needed to have a germline VHL alteration, at least 1 measurable RCC tumor per RECIST 1.1 criteria, no RCC tumor larger than 3 cm that required immediate surgical intervention, no evidence of metastatic disease, no prior exposure to systemic anticancer therapy, and an ECOG performance status of 0 or 1.

All patients received oral belzutifan at 120 mg once daily until unacceptable toxicity, disease progression, or patient withdrawal. The primary end point was independent review committee–assessed ORR per RECIST 1.1 criteria. Secondary end points included DOR, time to response, and progression-free survival.

Prior safety data from LITESPARK-004 demonstrated that all patients with CNShemangioblastomas (n = 50) had an any-grade adverse effect (AE), and 46% of these patients had a grade 3 to 5 AE. The most common any-grade AEs were anemia (90%), fatigue (70%), dizziness (50%), headache (40%), nausea (38%), and dyspnea (30%). The rates of serious AEs and treatment-related serious AEs were 32% and 8%, respectively. Two patients experienced grade 5 AEs.

In December 2023, belzutifan also received FDA approval for the treatment of patients with advanced RCC after prior therapy with a PD-1 or PD-L1 inhibitor and a VEGF TKI. The approval was supported by findings from the phase 3 LITESPARK-005 trial (NCT04195750).⁴ The agent is currently being examined in advanced RCC and other tumor types both as monotherapy and as a combination regimen component in other phase 2 and 3 studies.¹

References

1. Merck’s WELIREG (belzutifan) approved in China for the treatment of adult patients with certain types of Von Hippel-Lindau (VHL) disease-associated tumors. News release. News release. Merck. November 22, 2024. Accessed November 22, 2024. https://www.merck.com/news/mercks-welireg-belzutifan-approved-in-china-for-the-treatment-of-adult-patients-with-certain-types-of-von-hippel-lindau-vhl-disease-associated-tumors/
2. FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. News release. FDA. August 13, 2021. Accessed November 22, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-cancers-associated-von-hippel-lindau-disease
3. Iliopoulos O, Iversen AB, Narayan V, et al. Belzutifan for patients with von Hippel-Lindau disease-associated CNS haemangioblastomas (LITESPARK-004): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2024;25(10):1325-1336. doi:10.1016/S1470-2045(24)00389-9
4. FDA approves belzutifan for advanced renal cell carcinoma. FDA. December 14, 2023. Accessed November 22, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-advanced-renal-cell-carcinoma?utm_medium=email&utm_source=govdelivery