Rhythm Pharmaceuticals has announced that the US Food and Drug Administration (FDA) has approved an expanded indication for IMCIVREE (setmelanotide) to treat patients living with acquired Hypothalamic Obesity (HO), a rare disease characterised by accelerated and sustained weight gain caused by an injury to the hypothalamus or hypothalamic dysfunction. IMCIVREE is indicated to reduce excess body weight and maintain reduction long term in adults and paediatric patients aged four years and older with acquired HO.

“IMCIVREE is now the first and only FDA-approved therapy for acquired HO, offering a targeted approach that addresses the underlying biology of this disease and meets a critical unmet need for patients who previously had no treatment options. This is a transformative milestone for Rhythm and reinforces our commitment to bringing meaningful therapies to patients living with rare MC4R pathway diseases,” said David Meeker, MD, Chairman, Chief Executive Officer (CEO) and President, Rhythm.

The MC4R pathway is responsible for controlling physiological functions such as energy expenditure, hunger and weight regulation. Acquired HO most frequently follows tumours and their treatment or other hypothalamic injury or dysfunction. Based on analysis of the literature, tumour registries and claims data, Rhythm estimates there are approximately 10,000 people living with acquired HO in the US.

“Having a therapy for individuals and families affected by acquired hypothalamic obesity has the potential to be transformational. We’ve seen first-hand the devastating impact acquired Hypothalamic Obesity has on patients’ and families’ lives, including relentless hunger and accelerated and sustained weight gain. IMCIVREE offers hope and a path forward for thousands of patients who have long been without options,” said Amy Wood, Executive Director and Founder, Raymond A Wood Foundation.

The approval is supported by the positive pivotal phase-III TRANSCEND trial of setmelanotide in 142 patients with acquired HO. The global study met its primary endpoint, with a statistically significant -18.4 percent placebo-adjusted reduction in Body Mass Index (BMI). For the primary endpoint of mean BMI change from baseline, study participants on setmelanotide therapy (n=94) achieved a -15.8 percent reduction compared with a +2.6 percent increase among patients on placebo (n=48) at 52 weeks (p<0.0001). Setmelanotide was generally well tolerated in the phase-III trial. The most common adverse events (affecting >20 percent of participants) were skin hyperpigmentation, nausea, vomiting and headache.

“Setmelanotide has shown effectiveness in targeting the underlying biology of acquired HO. Patients treated with setmelanotide experienced meaningful reductions in BMI and hunger, demonstrating the therapy’s ability to deliver clinically significant outcomes in both children and adult patients. Acquired HO is a severe disease that requires early and proactive management. With the availability of IMCIVREE, physicians can offer a targeted therapy," said Ashley Shoemaker, MD, MSCI, Associate Professor of Paediatrics, Paediatric Endocrinology, Vanderbilt Health.

IMCIVREE (setmelanotide) is also approved in the US and Europe in adult and paediatric patients aged two years and older with syndromic or monogenic obesity due to Bardet-Biedl Syndrome (BBS) or Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency.