Landmark clinical trial results in first FDA-approved treatment for acquired hypothalamic obesity
Children and adults living with a rare condition that causes rapid, uncontrollable weight gain now have a new treatment option following the U.S. Food and Drug Administration’s approval of setmelanotide, based on results from the phase 3 TRANSCEND clinical trial, published in The New England Journal of Medicine
Reema Habiby, MD, chief of Endocrinology in the Department of Pediatrics and head of endocrinology at Ann & Robert H. Lurie Children’s Hospital of Chicago, served as co-author and site investigator of the international clinical trial
The study is the largest and longest clinical trial ever conducted for people with acquired hypothalamic obesity, a rare condition that can develop after damage to the part of the brain that controls hunger and body weight. It most often affects children after treatment for certain brain tumors. The publication highlights robust improvements in weight and hunger achieved with setmelanotide therapy in adult and pediatric patients aged four years and older
“For many families, this condition is heartbreaking,” Habiby said. “Children gain weight rapidly despite their best efforts to eat healthy and stay active because the part of the brain that tells the body when it’s full has been damaged and energy expenditure is also low. Until now, there has not been an approved treatment that addressed the underlying cause of the disease. These results offer real hope to children and families who have had very few options.”
Participants received either setmelanotide or a placebo for one year. The study found that people treated with setmelanotide:
- Lost significantly more weight than those who received a placebo.
- Experienced an average 16.5 percent reduction in body mass index (BMI), while people receiving the placebo saw an average 3.3 percent increase in BMI.
- Eight out of every 10 participants receiving the medication reduced their BMI by at least 5 percent.
- Reported meaningful improvements in hunger, an important symptom that can make the condition especially difficult to manage.
The medication was generally well tolerated, and researchers did not identify any new safety concerns during the study
Acquired hypothalamic obesity is caused by damage to the hypothalamus, a small but important area of the brain that regulates hunger, fullness and how the body uses energy. Because these signals no longer work properly, patients can experience constant hunger, slowed metabolism and rapid weight gain that is often resistant to diet and exercise alone. The condition most commonly develops after surgery or treatment for brain tumors, but it can also occur after a traumatic brain injury, stroke or severe inflammation.
“This approval represents years of collaboration among researchers, physicians, patients and families around the world,” Habiby said. “We’re excited to be able to offer a treatment that addresses the biology of this disease rather than simply trying to manage its symptoms.”
Lurie Children’s continues to lead research aimed at bringing innovative treatments to children with rare endocrine and metabolic disorders, helping families gain access to promising therapies through clinical trials and advanced specialty care
About the Phase 3 TRANSCEND Trial
The global, randomized, double blind, placebo-controlled phase 3 TRANSCEND trial evaluated the efficacy and safety of setmelanotide in patients aged 4 years and older with acquired hypothalamic obesity. A total of 120 participants were randomized 2:1 to once daily subcutaneous setmelanotide or placebo for 52 weeks. The primary endpoint was mean percent change in BMI after 52 weeks of treatment. Full topline results were previously announced in April 2025
About Ann & Robert H. Lurie Children’s Hospital of Chicago
Ann & Robert H. Lurie Children’s Hospital of Chicago is a nonprofit organization committed to providing access to exceptional care for every child. It is the only independent, research-driven children’s hospital in Illinois and one of less than 35 nationally. This is where the top doctors go to train, practice pediatric medicine, teach, advocate, research and stay up to date on the latest treatments. Exclusively focused on children, all Lurie Children’s resources are devoted to serving their needs. Research at Lurie Children’s is conducted through Stanley Manne Children’s Research Institute, which is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is the pediatric training ground for Northwestern University Feinberg School of Medicine. It is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report and Newsweek.
