Long-term use of Imcivree helps children, adults with aHO lose weight
Trial data also show benefits with new Rhythm therapy bivamelagon
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Scales and measuring tapes are used as tools in assessing obesity-targeting drugs in clinical trials. (Photo by iStock)
Treatment with Imcivree (setmelanotide), Rhythm Pharmaceuticals’ approved injection therapy for acquired hypothalamic obesity (aHO), helped children and adults with the rare obesity disorder lose body weight over as long as 2.5 years, according to new data from clinical trials.
In addition, Rhythm‘s experimental oral treatment bivamelagon was shown in another clinical trial to reduce weight and hunger for more than one year among people with aHO. Excessive hunger, known as hyperphagia, is a common symptom of aHO.
These results, presented during the recent Endocrine Society Annual Meeting (ENDO 2026), add to growing evidence that medications that activate the melanocortin 4 receptor (MC4R) — such as Imcivree and bivamelagon — are effective at treating aHO and other rare forms of obesity.
“We are excited to share positive results across these diseases showing MC4R [activation] continues to demonstrate its potential to meaningfully reduce hyperphagia and improve weight-related outcomes in these patients,” David Meeker, MD, Rhythm’s chairman, CEO, and president, said in a company press release announcing the new trial data.
In aHO, damage to a region of the brain called the hypothalamus disrupts signals — including those from the MC4R signaling pathway — that control hunger and how the body balances energy. As a result, patients may experience persistent hunger and burn fewer calories at rest, leading to rapid and continued weight gain.
Administered via under-the-skin (subcutaneous) injections, Imcivree is designed to restore MC4R signaling, which is expected to reduce excessive eating and help patients lose body weight. It was approved this year in the U.S. and the European Union for treating obesity and controlling hunger in aHO patients, ages 4 and older. The therapy had previously been cleared for use by people with other types of genetic obesity.
Imcivree linked to 16.5% cut in BMI in trial
Imcivree’s approvals for aHO were largely supported by results from a Phase 3 clinical trial, dubbed TRANSCEND (NCT05774756) and conducted at 28 study locations in North America, Europe, and Japan. The trial tested a daily subcutaneous injection of Imcivree against a placebo for one year in 120 children and adults with aHO.
Use of the therapy was associated with a mean 16.5% reduction in participants’ body mass index (BMI), a ratio of height and weight used as a proxy of body fat, data showed. That compared with a 3.3% increase among those receiving the placebo.
The findings were shared at ENDO in a poster titled “Weight Category Improvement Following Setmelanotide in Patients with Acquired Hypothalamic Obesity.” The data showed that, in TRANSCEND, Imcivree helped patients move into healthier weight categories after one year of treatment. Moving down one or more categories can represent a clinically meaningful improvement in health, per researchers.
Among children treated with Imcivree, most (71%) improved by at least one weight category, compared with 14% of those receiving the placebo. Similar results were seen in adults, with nearly three-quarters of Imcivree-treated patients improving by at least one category compared with 7% of those given the placebo.
Larger improvements were seen for many patients, the researchers noted. About 44% of children and 50% of adults receiving Imcivree improved by two or more weight categories, while no patients on the placebo achieved this level of improvement. After one year, 44% of Imcivree-treated participants reached either the overweight or healthy-weight range, whereas no participant on the placebo reached a healthy-weight category.
Weight loss also seen with treatment for those who had surgery
Additional TRANSCEND data from six adult participants who had undergone bariatric surgery were also shared in a poster titled “Setmelanotide Treatment in Patients With Acquired Hypothalamic Obesity and Previous Weight Loss Surgery.”
Despite having had bariatric surgery to lose weight, the participants had remained obese before entering the study. Four were treated with Imvicree, while two were given the placebo. Four of them completed the trial. Among the three participants who received Imvicree, BMI decreased by 9.6% to 37.9% after one year. In contrast, the one patient who received the placebo experienced a 4.8% increase in BMI.
In an oral presentation titled “Long-Term Efficacy with Setmelanotide in Patients with Acquired Hypothalamic Obesity,” scientists also shared long-term data from 11 children and adults with aHO who received Imcrivee for as long as 2.5 years in a Phase 2 trial (NCT04725240) and its long-term extension study (NCT03651765).
Data showed that Imcrivee treatment was associated with an average BMI drop of 18.9%. In pediatric patients, the BMI z-score, which compares a child’s BMI with that of others of the same age and sex, decreased by 1.6 points, indicating a reduction in body weight, the data showed.
The therapy’s safety profile over a longer term was consistent with that reported in previous trials. The most commonly reported adverse events were nausea, affecting 57% of patients, and darkening of the skin, experienced by 50%. Nose and throat infections and vomiting each affected 43% of participants.
Use of experimental therapy bivamelagon also eased obesity
The researchers also presented new trial data on bivamelagon, an experimental oral medication that works in a way similar to Imcivree. That poster was titled “Weight Reduction After 1 Year of Oral Bivamelagon in Acquired Hypothalamic Obesity.”
In a Phase 2 study (NCT06046443), aHO patients ages 12 and older received either bivamelagon or a placebo daily for 14 weeks, or about three months. Those completing this part of the trial could enter its open-label extension portion, in which all received the therapy for as long as 38 weeks, or nearly nine months. Altogether, the study periods totaled as long as one year of treatment.
Those results showed that, depending on the dose received, average BMI reductions ranged from 6.7% to 16.6%, with the greatest weight loss seen for participants who received the highest dose (600 mg) throughout the study.
While most participants initially given the placebo gained weight during the 14-week placebo-controlled portion, “BMI decreased over the subsequent 38 weeks after initiation of bivamelagon 600 mg,” the researchers wrote.
Maximal daily hunger scores also showed a reduction of 1.9 to 4.8 across doses. In children, BMI z-scores decreased modestly, the data showed. The most commonly reported adverse events were vomiting, nausea, diarrhea, and headache.
