Following the reasonably good preliminary results of Welireg (belzutifan) in combination with cabozantinib (Cabometyx) in ccRCC(clear cell renal cell carcinoma) patients, which Merck presented in ASCO 2021, the company is planning to further present positive results of the drug combination in Phase II for advanced ccRCC during this year’s ESMO. (Abstract #656MO)
Acquired from Peloton Therapeutics, Merck’s Welireg, a HIF-2α inhibitor, was recently approved by the FDA as the only non-surgical, first-line treatment of VHL-associated RCC. DelveInsight estimates that there will be approximately 2,445 VHL-associated RCC patients in the United States in 2021. Apart from RCC, Welireg has also been approved for von Hippel-Lindau (VHL) disease, which requires therapy for the central nervous system (CNS) hemangioblastomas or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.
Welireg’s approval was based on efficacious Phase II data and, fortunately with a priority review under its belt, was approved earlier than the designated PDUFA date of September 15, 2021. By combining Exelixis’ cabozantinib with its belzutifan, Merck wants to bolster its presence in the RCC market with a combination regimen. With cabozantinib monotherapy demonstrating a 20% ORR in 1L RCC, along with its approval in combination with Opdivo (nivolumab) in the 1L setting for advanced RCC, the drug combination (cabozantinib + nivolumab) is expected to give encouraging results in ccRCC patients.
The company is conducting the Phase II trial in two cohorts: Cohort 1 and Cohort 2. While Cohort 1 includes advanced ccRCC patients who have not received any previous therapy for the disease (1L), Cohort 2 is being conducted in advanced ccRCC patients who have received no more than two prior treatments or immunotherapy (2L and 3L). The results will be presented on September 18, 2021, as a mini oral presentation and might give an idea of how the drug combination will fare in the future. Considering that the results are promising, the approval of this drug combination could be expected to follow a path similar to that of belzutifan’s approval of VHL-associated RCC. In addition, the company is also conducting another Phase I/II combination trial of pembrolizumab with cabozantinib in patients with metastatic RCC.
For the latest analysis on the epidemiological and market forecast of the overall VHL disease, refer to DelveInsight’s Von Hippel-Lindau disease Market Insights, Epidemiology, and Market Forecast – 2030.