Imcivree cuts diabetes risk, lowers BMI in rare obesity studies
Clinical trial, real-world analyses show benefits for acquired hypothalamic obesity
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A person steps on a scale.
Imcivree (setmelanotide) reduced the risk of metabolic complications such as diabetes or steatotic liver disease in people with acquired hypothalamic obesity (aHO), according to new analyses from a global clinical trial.
In real-world analyses, Imcivree was also associated with reductions in body mass index (BMI) — a ratio of weight and height commonly used as a proxy of body fat — consistent with previous clinical trial findings.
These and other aHO data were discussed in a series of posters at the European Congress of Endocrinology, held last month in Prague. They were sponsored by Imcivree’s developer, Rhythm Pharmaceuticals.
A rare form of obesity, aHO is caused by damage to the hypothalamus, a brain region that regulates hunger and energy use. Consequently, people living with the disease experience symptoms such as excessive hunger and burn fewer calories at rest, leading to accelerated and continuous weight gain.
Imcivree, administered as a daily under-the-skin (subcutaneous) injection, is approved in the U.S. and European Union to help promote and maintain weight loss in aHO patients ages 4 and older. It works by restoring activity of the MC4R signaling pathway, one of the hunger-regulating pathways that is disturbed by aHO-related damage.
Additional analysis
The therapy’s regulatory approvals for aHO were supported by data from the Phase 3 TRANSCEND clinical trial (NCT05774756), which showed that Imcivree led to significantly greater BMI reductions than a placebo.
In one of the conference posters, researchers presented additional analyses from TRANSCEND that focused on how Imcivree affected the risk of metabolic complications. It was titled “Impact of Setmelanotide on Metabolic Index Scores in Phase 3 Trial Participants with Acquired Hypothalamic Obesity.”
The analysis covered 120 participants, ranging in age from 4 to 66. Eighty-one received Imcivree and 39 received a placebo. The researchers looked at a number of metabolic index scores that use routinely available clinical measures to estimate a person’s risk of complications such as diabetes, steatotic liver disease (marked by excess fat in the liver), or high blood levels of cholesterol (a fatty molecule). Across all index scores, Imcivree was associated with significantly greater reductions in metabolic risk after a year compared with the placebo.
“The findings highlight the broad metabolic benefits and strong clinically meaningful efficacy of [Imcivree] in this population,” the researchers wrote in the poster. They noted, however, that while the study included both children and adults, these metabolic risk scoring systems have not been validated in pediatric populations.
In another poster, titled “Real-World BMI Outcomes in Adult Patients with Acquired Hypothalamic Obesity Treated With Setmelanotide for up to 12 Months in France,” scientists discussed real-world data on the use of Imcivree among adults with aHO in France.
The analysis looked at 62 adults (mean age 34.4) who received Imcivree for up to a year through an early access program, which allows patients to access experimental therapies before their potential approval. All had obesity at the start of treatment (baseline).
Among the 39 participants who reached six months of treatment, Imcivree led to a significant 13% reduction in mean BMI from baseline. Available data at nine and 12 months showed sustained reductions of 19.6% and 16.9%, respectively.
Most participants experienced a BMI reduction of at least 10% after six, nine, or 12 months of treatment.
Patients’ weight class (i.e., healthy, overweight, obese) also showed improvements. Eighteen percent of participants with six-month data were no longer obese, as was the case for 34.6% of those with nine-month results. At the one-year mark, 28% of people with available data were no longer obese.
A total of 37 people, ages 12 and older, who received Imcivree for at least six months responded to patient-reported questionnaires about hunger. Data showed reductions in hunger at all time points. The therapy’s safety profile was consistent with that reported in trials.
These findings “contribute to the understanding of the real-world therapeutic value of [Imcivree] as a targeted treatment for patients with aHO,” the researchers wrote in the poster.
In the third poster, “Recognising the Burden of Acquired Hypothalamic Obesity in Craniopharyngioma: Cross-Country Insights from Lived Experiences to Support Integrated Care Across All Life Stages,” researchers looked at the burden of living with childhood-onset craniopharyngioma (CP), a type of noncancerous brain tumor that is the leading cause of aHO.
Researchers conducted online and in-person interviews with 33 people with CP and their family members across the Netherlands, Germany, and the U.K. Participants reported a wide range of burdensome symptoms and quality-of-life impacts. Many reported symptoms were consistent with aHO, including excessive hunger, fatigue, reduced stamina, and weight gain.
The transition from pediatric to adult care was also reportedly abrupt and inconsistent, with many unmet care needs.
“As many reported symptoms are associated with aHO, it emerges as a key long-term [neurohormonal] consequence of CP,” the researchers wrote. “This underscores the need for aHO to be a central focus of CP management, research, care planning, clinical guidelines, and healthcare resource allocation.”
