Merck announces results from Phase 3 LITESPARK-005 trial investigating WELIREG

Merck announced results from the Phase 3 LITESPARK-005 trial investigating WELIREG, Merck’s first-in-class, oral hypoxia-inducible factor-2 alpha inhibitor, for the treatment of adult patients with advanced renal cell carcinoma that progressed following PD-1/L1 and vascular endothelial growth factor receptor targeted therapies. In the study, WELIREG demonstrated a statistically significant improvement in one of the trial’s dual primary endpoints of progression-free survival and in a key secondary endpoint of objective response rate compared to everolimus. These late-breaking data were presented for the first time today during a proffered paper session at the European Society for Medical Oncology Congress 2023 and are also being discussed with regulatory authorities worldwide. At the first pre-specified interim analysis at a median follow-up of 18.4 months, WELIREG significantly reduced the risk of disease progression or death by 25% versus everolimus in these patients. Results at the second pre-specified interim analysis were consistent with IA1. At a median follow-up of 25.7 months, WELIREG reduced the risk of disease progression or death by 26% versus everolimus. Treatment with WELIREG was also associated with a statistically significant improvement in ORR at IA1; the ORR was 21.9%, with a complete response rate of 2.7%, for patients who received WELIREG versus an ORR of 3.5%, with no patients achieving a CR rate, for patients who received everolimus. At IA2, the ORR was 22.7%, with a CR rate of 3.5% for patients who received WELIREG versus a 3.5% ORR, with no patients achieving a CR rate, for patients who received everolimus. Additionally, overall survival, the trial’s dual primary endpoint, favored WELIREG versus everolimus and at IA1 and IA2, respectively; however, this result did not reach statistical significance. Additional data from the LITESPARK clinical development program being presented at the ESMO Congress 2023 include Phase 2 results from the LITESPARK-003 and LITESPARK-013 trials evaluating WELIREG in advanced RCC. As announced, data spanning more than 15 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the ESMO Congress 2023, in addition to a Merck-sponsored study evaluating the impact of Von-Hippel Lindau disease-associated tumor treatment on mental health. WELIREG is a first-in-class, HIF-2alpha inhibitor therapy approved in the U.S. for the treatment of adult patients with VHL disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery based on data from the Phase 2 LITESPARK-004 trial. Additional applications are currently under regulatory agency review worldwide based on LITESPARK-004. LITESPARK-005 is part of a comprehensive development program for WELIREG, comprised of four Phase 3 trials in RCC, including LITESPARK-011 and LITESPARK-012, evaluating WELIREG in the second-line and treatment-naive advanced disease settings, and LITESPARK-022, evaluating WELIREG in the adjuvant setting. Merck previously announced that based on these positive results from LITESPARK-005, the U.S. Food and Drug Administration has granted priority review for a supplemental new drug application for WELIREG for the treatment of adult patients with advanced RCC following immune checkpoint and anti-angiogenic therapies. The FDA has set a Prescription Drug User Fee Act, or target action, date of January 17, 2024.