The results of domestic clinical trials of besotivan are exposed and authoritatively interpreted!

China's National Medical Products Administration (NMPA) has approved Belzutifan-Welireg for the treatment of adult patients with von Hippel-Lindau (VHL) who require treatment-associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastoma, or pancreatic neuroendocrine tumors (pNETs) who do not require immediate surgery. The regulatory decision is the 17th global approval for patients with these diseases.

Objective response rate (ORR) and median duration of response (DOR) data from the LITESPARK-004 Phase 2 trial (NCT03401788) support the NMPA's decision. The ORR in patients with VHL-associated renal cell carcinoma was 49% (95% CI, 36%-62%); all responses were partial. The median DOR has not been reached (NR; range 2.8+ to 22.3+), and 17 of 30 responding patients maintained their response for at least 12 months.

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

The approval of besetivan brings the first and only systemic treatment to certain adult patients in China with VHL-related tumors who have until now had no access to non-surgical treatment options to help manage the manifestations of VHL disease. The approval of besetifanprovides first-in-classHIF-2α inhibitors as a possible treatment option for eligible adult patients in China.

In August 2021, the U.S. Food and Drug Administration approved bestivan for the treatment of adult patients with VHL disease who require treatment for renal cell carcinoma, central nervous system hemangioblastoma, or pNETs that do not require immediate surgery. The results of LITESPARK-004 also support this regulatory decision.

LITESPRAK-004 is a multicenter, open-label, single-arm study enrolling adult patients with VHL disease-associated RCC and other related tumors in the United States, Denmark, France and the United Kingdom. 3 Eligible patients were required to have germline VHL alterations, at least 1 measurable RCC tumor according to RECIST 1.1 criteria, no RCC tumors larger than 3 cm requiring 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 were given 120 mg of bestivan orally once daily until unacceptable toxicity, disease progression, or patient discontinuation. The primary endpoint was independent review committee-assessed ORR according to RECIST 1.1 criteria. Secondary endpoints include DOR, time to response, and progression-free survival.

Prior safety data for LITESPRAK-004 demonstrated that all patients with CNS hemangioblastoma (n=50) had any grade adverse effect (AE), with 46% of patients having grade 3 to 5 AEs. The most common any-grade AEs were anemia (90%), fatigue (70%), dizziness (50%), headache (40%), nausea (38%), and dyspnea (30%). The incidence of serious adverse events and treatment-related serious adverse events were 32% and 8%, respectively. Two patients experienced grade 5 adverse events.

In December 2023, bezutivan also received approval from the U.S. Food and Drug Administration for the treatment of patients with advanced renal cell carcinoma who were previously treated with a PD-1 or PD-L1 inhibitor and a VEGF TKI. The approval is supported by results from the Phase 3 LITESPRAK-005 trial (NCT04195750). The drug is currently being examined in advanced renal cell carcinoma and other tumor types as monotherapy and as a component of combination regimens in other Phase 2 and 3 studies.

Reference: https://www.onclive.com/view/nmpa-approves-belzutifan-for-vhl-in-rcc-cns-hemangioblastomas-or-pnets