UT Southwestern researchers (l-r) Kevin Courtney, M.D., Ph.D.; James Brugarolas, M.D., Ph.D.; Richard Bruick, Ph.D.; Steven McKnight, Ph.D.; and David Russell, Ph.D., were among those involved with the scientific discoveries that helped make belzutifan a reality as a therapy for millions of people worldwide with kidney cancer.
Newswise — DALLAS – Dec. 15, 2023 – The U.S. Food & Drug Administration has expanded the approved use of belzutifan for treatment of metastatic kidney cancer, another milestone for the novel, first-in-class kidney cancer drug arising from scientific discoveries at UT Southwestern Medical Center.
Following the discovery of the hypoxia-inducible factor 2-alpha (HIF-2α) gene at UT Southwestern, its scientists solved the HIF-2α protein structure, pinpointing a potential vulnerability. The UTSW team then conducted a comprehensive drug screen to identify possible therapeutic compounds and established Peloton Therapeutics, which developed the drug. Peloton was ultimately acquired by the pharmaceutical giant Merck, which markets belzutifan under the brand name Welireg.
Belzutifan was initially approved by the FDA in 2021 for familial kidney cancer. The latest approval follows completion of the Litespark-005 phase three clinical trial and broadens the drug’s label to anyone with advanced renal cell carcinoma.
“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,” said James Brugarolas, M.D., Ph.D., Professor of Internal Medicine in the Division of Hematology and Oncology and founding Director of the Kidney Cancer Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “With the FDA’s approval, thousands of patients in need will gain access to this important new treatment.”
Mark Hilz, a 65-year-old Texas businessman who enjoys spending time with his eight grandchildren, was first diagnosed with kidney cancer in 2011. By May 2023, he was running out of options that would preserve his outstanding quality of life. Dr. Brugarolas recommended belzutifan, and it made a difference, reducing the size of some tumors and stopping the growth of others.
“It was starting to look like I had an expiration date,” said Mr. Hilz, who takes three pills daily to keep his cancer under control. “Imagine being stage 4 and then getting a restart. I’m also able to maintain a great quality of life on this treatment.”
A journey of innovation
HIF-2α was discovered by Steven McKnight, Ph.D., Professor of Biochemistry, and David Russell, Ph.D., Professor Emeritus of Molecular Genetics, at UT Southwestern. The gene was subsequently found to play a key role in the growth of kidney cancer. UTSW scientists Kevin Gardner, Ph.D., and Richard Bruick, Ph.D., then studied the protein structure, identifying an unusual cavity within HIF-2α and demonstrating that chemical compounds could bind to that vulnerable area.
Led by Drs. Bruick and Gardner, the next phase involved a rigorous drug screen of UT Southwestern’s chemical library to identify specific compounds that could block HIF-2α function. Building on their momentum, UT Southwestern incubated Peloton Therapeutics within its BioCenter and transformed the scientific innovation into a tangible therapy.
Dr. Brugarolas tested mice transplanted with human kidney cancers and determined that the drug was effective against the tumors. Kevin Courtney, M.D., Ph.D., Associate Professor of Internal Medicine and Chair of the Protocol Review & Monitoring Committee of the Simmons Cancer Center, conducted the first clinical trial of a HIF-2α inhibitor and found the drug to be well-tolerated and effective among patients with kidney cancer. More than half of the participants saw their cancer regress or stabilize with the drug. Drs. Brugarolas and Courtney then established that HIF-2α is a core dependency for many kidney tumors.
Merck recognized the drug’s transformative potential and acquired Peloton in 2019.
In 2021, the FDA approved belzutifan for adult patients with von Hippel-Lindau (VHL) disease, a familial kidney cancer condition. VHL patients develop renal cell carcinoma, central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors, and all of those types respond to the therapy.
In 2023, results were reported from a phase three trial evaluating belzutifan for treatment of clear cell renal cell carcinoma that progressed on prior immune and targeted therapies. The study showed a statistically significant and clinically meaningful delay in tumor progression compared with everolimus, the former standard of care. These results led to an expanded FDA approval on Dec. 14 to treat the most common type of kidney cancer.
Cancer care at UTSW
The Kidney Cancer Program within UTSW’s Simmons Cancer Center is one of only two National Cancer Institute-designated Specialized Programs of Research Excellence (SPOREs) in kidney cancer. Established in 2013, the program has become a leader worldwide in kidney cancer.
The Simmons Cancer Center is one of 33 members of the National Comprehensive Cancer Network and one of 56 National Cancer Institute-Designated Comprehensive Cancer Centers. The Simmons Cancer Center is ranked 19th for cancer care among over 800 cancer hospitals by U.S. News & World Report. Its faculty members treat more than 9,000 new cancer patients a year, participate in over 300 active clinical trials, and have more than $100 million in extramural cancer-focused research funding.
Dr. Brugarolas holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. Dr. McKnight holds the Distinguished Chair in Basic Biomedical Research.
Disclosures: UT Southwestern and some of its researchers will receive financial compensation, through prior agreements with Peloton, based on belzutifan’s FDA approval.
Related Stories
- New HIF-2 kidney cancer therapy more effective than current treatment, study shows
- New class of anti-cancer drug effective against kidney cancer
- Clinical trial exposes deadly kidney cancer's Achilles' heel
- FDA approval of belzutifan culminates 25-year journey at UTSW from gene discovery to a first-in-class drug
- Kidney Cancer Program Report
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.
RSS