Merck, recognized globally as MSD outside the Americas, has announced that China’s National Medical Products Administration (NMPA) has granted approval for Welireg (belzutifan) to be used in adult patients with von Hippel-Lindau (VHL) disease who need treatment for associated tumors such as renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET) that do not necessitate immediate surgery.
Welireg represents a pioneering oral inhibitor targeting hypoxia-inducible factor-2 alpha (HIF-2a), marking it as the first and sole authorized HIF-2a inhibitor in the Chinese market. The endorsement is grounded on objective response rate (ORR) and the median duration of response (DOR) outcomes from the phase 2 LITESPARK-004 clinical trial, positioning this as the 17th global clearance of Welireg for these particular patients.
“Welireg’s authorization introduces the only systemic treatment option to adult patients in China managing specific VHL disease-connected tumors, who until now lacked a non-surgical path for the manifestations of VHL disease,” commented Dr. Marjorie Green, Senior Vice President and Head of Oncology at Merck Research Laboratories. “We are dedicated to delivering groundbreaking treatments to those in need worldwide and are delighted to offer eligible adults in China this first-in-class HIF-2a inhibitor as a potential therapy.”
In the United States, Welireg received approval in August 2021 for adults with VHL disease needing intervention for linked RCC, CNS hemangioblastomas, or pNET, without the urgency for surgery. The LITESPARK-004 trial, a transparent clinical study involving 61 individuals with VHL-associated RCC, showcased a 49% ORR (95% CI, 36-62) in these patients (n=30/61), with all responses being partial. Median DOR wasn’t attained while ongoing responses extended from 2.8+ to 22.3+ months, with 56% (n=17/30) of responders experiencing a sustained response over 12 months.
Participants in LITESPARK-004 also possessed other tumors tied to VHL, such as CNS hemangioblastomas and pNET. In the study, for those with VHL-linked CNS hemangioblastomas (n=24), Welireg achieved a 63% ORR (95% CI, 41-81) (n=15/24), including a 4% full response rate (n=1/24) and a partial response of 58% (n=14/24). The median DOR wasn’t achieved, with response durations varying from 3.7+ to 22.3+ months, with 73% (n=11/15) maintaining their response for a minimum of 12 months. For VHL-associated pNET patients (n=12), Welireg reached an 83% ORR (95% CI, 52-98) (n=10/12), featuring a 17% CR and 67% PR. The median DOR wasn’t reached, with response durations extending from 10.8+ to 19.4+ months, and 50% (n=5/10) sustained a year-long response.
In the U.S., Welireg is additionally sanctioned for adults with advanced RCC following treatment with a PD-1 or PD-L1 inhibitor and a VEGF-TKI, informed by phase 3 LITESPARK-005 trial findings. Merck is exploring Welireg’s potential in advanced RCC and other cancers via an expansive clinical development program, encompassing both phase 2 and 3 trials in solo therapy and combination regimens.
The LITESPARK-004 is a transparent phase 2 study (ClinicalTrials.gov, NCT03401788) examining Welireg’s efficacy for patients with VHL disease harboring at least one measurable kidney-specific solid tumor sans immediate surgery necessity. The trial included 61 individuals treated with Welireg (120 mg orally per day) until disease advancement or unaccepted toxicity appeared. The principal focus was on ORR in VHL disease-associated RCC. Secondary metrics in RCC tumors encompassed disease control rate, DOR, response timing, progression-free survival, surgery timing, and safety. The study also inspected the response in other prevalent VHL-associated tumors like pNET and CNS hemangioblastomas.
Von Hippel-Lindau disease, a rare genetic disorder, affects roughly 200,000 people globally. Individuals with VHL are vulnerable to recurring benign and some malignant blood vessel tumors. Renal cell carcinoma, a kidney cancer variant, is frequently occurring in approximately 70% of those with VHL disease.
Welireg (belzutifan) is designated for treating adult VHL patients needing therapy for linked RCC, CNS hemangioblastomas, or pNET without needing direct surgery, as well as adults with advanced RCC post PD-1 or PD-L1 inhibitor and a VEGF-TKI treatment.