Boston, Massachusetts, August 11, 2026
Rhythm Pharmaceuticals announced that the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has expanded the marketing authorization for IMCIVREE® (setmelanotide) to include the treatment of obesity and control of hunger in adults and children 4 years of age and older with acquired hypothalamic obesity (HO) caused by hypothalamic injury or impairment. The MHRA also granted orphan drug designation to IMCIVREE for acquired HO, marking an important regulatory milestone for patients living with this rare neuroendocrine disorder.
IMCIVREE Gains Expanded UK Authorization
Acquired hypothalamic obesity is a rare and complex condition associated with injury or impairment of the hypothalamus, which can disrupt biological pathways responsible for regulating hunger, energy balance and body weight. The condition frequently develops following the growth or treatment of hypothalamic-pituitary tumors, including craniopharyngioma and astrocytoma, although traumatic brain injury, stroke, inflammation and anatomical abnormalities can also contribute. Patients may experience rapid and sustained weight gain, excessive hunger and reduced energy expenditure, creating significant long-term health and quality-of-life challenges. Rhythm Pharmaceuticals estimates that approximately 10,000 people in Europe are living with acquired hypothalamic obesity. IMCIVREE is designed to address the underlying biology of obesity associated with impaired melanocortin-4 receptor (MC4R) pathway signaling. The treatment previously received UK marketing authorization in 2021 for patients with obesity and hunger associated with POMC, PCSK1 or LEPR deficiency and was expanded in 2022 to include patients with Bardet-Biedl syndrome (BBS). In 2024, the authorization was further expanded to include children as young as two years old for certain approved indications. The latest MHRA decision adds acquired hypothalamic obesity to the UK treatment landscape.
TRANSCEND Trial Supports Regulatory Decision
The expanded authorization was supported by results from the Phase 2 and Phase 3 TRANSCEND clinical trials evaluating setmelanotide in acquired hypothalamic obesity. The global 120-patient TRANSCEND study achieved its primary endpoint, demonstrating a statistically significant 19.8% placebo-adjusted reduction in body mass index (BMI) at Week 52. Patients receiving setmelanotide achieved a mean BMI reduction of 16.5%, compared with a 3.3% increase among patients receiving placebo, with the difference reaching statistical significance at p<0.0001. Adult participants achieved a 19.2% placebo-adjusted BMI reduction, while pediatric participants achieved a 20.2% reduction. Patients receiving treatment also experienced reductions in hunger, while setmelanotide was generally well tolerated. The TRANSCEND findings were recently published in The New England Journal of Medicine, further supporting the clinical evidence behind the regulatory decision. The company reported that the most common treatment-emergent adverse events affecting more than 20% of participants included nausea, vomiting, diarrhea, injection-site reactions, skin hyperpigmentation and headache.
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Expanded Access Advances Rare Disease Treatment
The UK authorization provides healthcare professionals with an approved treatment option for eligible patients with acquired hypothalamic obesity, a population that previously had no approved therapies in the UK for this condition. The regulatory decision also strengthens the development of targeted approaches that address specific biological mechanisms underlying rare forms of obesity rather than general weight-management pathways. Rhythm Pharmaceuticals plans to work with the United Kingdom’s National Health Service (NHS) to finalize guidance concerning coverage of IMCIVREE for acquired hypothalamic obesity. The latest authorization expands the potential patient population for setmelanotide, an MC4R agonist being developed by Rhythm for rare neuroendocrine diseases. The company is also advancing a broader clinical development program involving setmelanotide and investigational MC4R agonists, including bivamelagon and RM-718, while continuing research into treatments for additional rare diseases. The UK decision therefore represents both a significant regulatory milestone for IMCIVREE and another step in expanding targeted therapeutic options for patients with rare obesity disorders.
Source: Rhythm Pharmaceuticals press release
