Imcivree approved in EU to treat acquired hypothalamic obesity
Developer to work with each country to make treatment available
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The European Union flag is seen in front of the European Parliament in Brussels. (Photo by iStock)
The European Commission (EC) has approved Imcivree (setmelanotide) to treat obesity and control hunger in people ages 4 years or older with acquired hypothalamic obesity (aHO) caused by damage to the brain’s appetite-control center.
“This EC authorization is an important step toward making the first new treatment option available to people living with acquired HO in Europe,” David Meeker, MD, chairman, president, and CEO of Rhythm Pharmaceuticals, which markets Imcivree, said in a company press release. “We look forward to working with local health authorities to support access for patients who may benefit.”
Rhythm will now work with each country in the European Union to make the treatment available for the 10,000 children and adults estimated to live with aHO in Europe, with commercial launches expected in 2027.
The regulatory decision expanded the therapy’s use beyond reducing weight gain in certain types of genetic obesity. A similar label expansion occurred earlier this year in the U.S., where PANTHERx Rare Pharmacy will continue to distribute Imcivree for all approved indications, including aHO.
Regulatory agencies in Japan are also reviewing Imcivree as a potential therapy for aHO.
Patients on Imcivree experienced reduction in BMI during trial
In aHO, damage to a part of the brain called the hypothalamus disrupts signals that control hunger and energy use, including those from the melanocortin 4 receptor (MC4R) signaling pathway. As a result, patients feel constantly hungry and burn fewer calories at rest, leading to rapid and ongoing weight gain.
Imcivree, administered via under-the-skin (subcutaneous) injection, is designed to reactivate MC4R, which signals fullness after eating and helps the body burn more calories. This is expected to reduce excessive eating and help patients lose weight.
The therapy was first approved for chronic weight management in children and adults with obesity-causing mutations in the POMC, PCSK1, or LEPR gene, and later in those with Bardet-Biedl syndrome, a genetic disease that causes weight gain.
Imcivree’s approval for aHO was largely based on data from an international Phase 3 clinical trial, called TRANSCEND (NCT05774756), which tested a daily subcutaneous injection of Imcivree against a placebo in 120 aHO patients, including 71 children ages 4 to 17 years.
After one year, participants on Imcivree had a significant 19.8% reduction in body mass index (BMI), a ratio of weight and height commonly used as a proxy for body fat, compared with those on the placebo. Specifically, BMI dropped by a mean of 16.5% in the Imcivree group and increased by 3.3% in the placebo group.
The treatment was generally well tolerated. The most common side effects included nausea, vomiting, diarrhea, headache, hyperpigmentation (skin darkening), and reactions at the site of injection.
More children on Imcivree reached a healthier weight range
According to new trial data presented earlier this month at the Pediatric Endocrine Society meeting in San Francisco, most children (71.1%) moved to a lower weight category based on BMI after one year on Imcivree; nearly half (44.4%) improved by at least two categories.
More children on Imcivree reached a healthier weight range (healthy weight or overweight) than those on placebo (44.4% vs. 18.2%), with none in the placebo group reaching a healthy weight.
“Acquired hypothalamic obesity is a complex disease that requires long-term management, particularly in pediatric patients,” Jennifer Miller, MD, a professor at the University of Florida in Gainesville who presented the data, said in a press release from Rhythm announcing the results. “The data presented provide important longer-term insights into treatment response for pediatric patients treated with [Imcivree], including reductions across multiple weight-related measures.”
Data from an earlier Phase 2 trial (NCT04725240) and its long-term extension study (NCT03651765) were also presented at the meeting. Of the 12 children with acquired HO who entered the extension study after four months on Imcivree as part of the main study, 10 completed 2.5 years of treatment.
Overall, the clinically meaningful reductions in BMI observed in the main study were maintained over time. BMI decreased by a mean of 16.4% after 2.5 years of treatment with Imcivree. BMI Z-score, which compares a child’s BMI to that of others their age, decreased by 1.6 points, and %BMI95, which measures a child’s BMI relative to the 95th percentile (the technical cutoff for obesity), decreased by 34.2 percentage points.
Long-term treatment with Imcivree led to “robust and sustained reductions across age-related weight measures in pediatric patients with aHO,” the researchers wrote. Side effects were consistent with what had already been reported, confirming “the long-term efficacy and safety of [Imcivree] in patients with aHO.”
