HQ Team
June 16, 2026: The US Food and Drug Administration (FDA) has expanded approval of belzutifan, a first-in-class kidney cancer drug, to treat patients with earlier-stage kidney cancer in combination with an immunotherapy drug. The drug’s discovery traces back three decades to basic research at UT Southwestern Medical Center
The approval marks the latest expansion of belzutifan’s use since the drug, marketed by Merck under the brand name Welireg, was first approved by the FDA in 2021 for a rare, inherited form of kidney cancer.
A phase 3 trial spanning 285 sites
The newest approval is based on results from the LITESPARK-022 phase 3 clinical trial, conducted at 285 sites worldwide, including UT Southwestern. The trial evaluated belzutifan in combination with pembrolizumab, a checkpoint-inhibitor immunotherapy drug, in patients with clear cell renal cell carcinoma following surgery to remove the affected kidney. The results were presented at the 2026 ASCO Genitourinary Cancer Symposium.
“With the FDA’s approval, thousands of patients in need will gain access to this important new treatment,” said James Brugarolas, professor of internal medicine in the Division of Hematology and Oncology and founding director of the Kidney Cancer Program at UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center.
From a 1990s gene discovery to an approved drug
Belzutifan’s origins date to research conducted at UT Southwestern in the 1990s, when biochemistry professor Steven McKnight and molecular genetics professor emeritus David Russell discovered a protein called HIF-2α. Originally identified for its role in helping cells adapt to low-oxygen conditions, HIF-2α was later found to drive the growth of kidney cancer.
UT Southwestern scientists subsequently identified a druggable cavity within the HIF-2α protein and pursued inhibitor compounds that could bind to it, founding a company called Peloton Therapeutics to develop the work further. Peloton-led research, followed by UT Southwestern preclinical studies and first-in-human clinical trials, ultimately produced the drug now known as belzutifan. Merck acquired Peloton in 2019 and brought the drug to its current form.
The FDA first approved belzutifan in 2021 for adult patients with von Hippel-Lindau disease, a familial condition that predisposes patients to kidney cancer. By 2023, following the phase 3 LITESPARK-005 trial, the drug’s approved use had expanded to cover advanced renal cell carcinoma broadly, after results showed a statistically significant and clinically meaningful delay in tumour progression compared with everolimus, the prior standard of care.
What the expanded approval means for patients
The latest approval moves belzutifan into the adjuvant treatment setting, meaning patients can receive it after surgery, in earlier stages of disease, rather than only after cancer has already become metastatic. Combining the drug with pembrolizumab reflects a broader trend in oncology toward pairing targeted therapies with immunotherapy to attack tumours through multiple mechanisms simultaneously.
“This remarkable journey exemplifies UT Southwestern’s dedication to converting important scientific discoveries into improvements in patient care and underscores the power of innovation and team science in advancing health care,” Brugarolas said.
The Kidney Cancer Program at UT Southwestern’s Simmons Cancer Center is one of only two centres in the US designated by the National Cancer Institute as a Specialized Program of Research Excellence focused on kidney cancer, underscoring the institution’s continued role in the drug’s ongoing development.
Disclosure
UT Southwestern and some of its researchers are entitled to financial compensation, through prior agreements tied to Peloton Therapeutics, based on belzutifan’s FDA approvals.
The findings are also published in the Journal of Clinical Oncology.
