Children and adults with brain injury-linked obesity have a new therapy after the FDA approved setmelanotide.
The treatment is for acquired hypothalamic obesity, a rare condition that can cause rapid and difficult-to-control weight gain.
The condition can develop after damage to the hypothalamus, the part of the brain that helps regulate hunger, fullness and how the body uses energy.
The US Food and Drug Administration approved setmelanotide following results from the phase 3 TRANSCEND clinical trial.
The trial involved adults and children aged four and older with acquired hypothalamic obesity.
Reema Habiby, chief of endocrinology in the department of paediatrics and head of endocrinology at Ann & Robert H. Lurie Children’s Hospital of Chicago, was a co-author and site investigator.
“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.”
The study has been described as the largest and longest clinical trial conducted in people with acquired hypothalamic obesity.
The condition most often affects children after treatment for certain brain tumours, but it can also occur after traumatic brain injury, stroke or severe inflammation.
Study participants received either setmelanotide or a placebo, an inactive treatment used for comparison, for one year.
The trial was randomised, meaning participants were assigned to treatment groups by chance, and double-blind, meaning neither patients nor clinicians knew who received the drug or placebo during the study.
Researchers said people treated with setmelanotide lost significantly more weight than those who received a placebo.
Those given setmelanotide had an average 16.5 per cent reduction in body mass index, while those receiving placebo had an average 3.3 per cent increase.
Body mass index, or BMI, is a measure based on a person’s weight and height.
Eight out of 10 participants receiving setmelanotide reduced their BMI by at least five per cent.
Participants also reported meaningful improvements in hunger, a symptom that can make acquired hypothalamic obesity especially difficult to manage.
The medication was generally well tolerated, and researchers said no new safety concerns were identified during the study.
Setmelanotide was given once daily by subcutaneous injection, meaning it was injected under the skin.
“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.”
Topline results from the 120-participant trial were first announced in April 2025.
