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Rhythm Pharmaceuticals is pursuing approval for its rare obesity disorder drug Imcivree in acquired hypothalamic obesity after it showed a 19.8% weight loss in a Phase III trial.
The Boston-based biopharma reported positive topline data from the pivotal TRANSCEND trial, which evaluated Imcivree (setmelanotide), a subcutaneous melanocortin-4 receptor (MC4R) agonist, in patients with acquired hypothalamic obesity for 52 weeks. Acquired hypothalamic obesity is a rare form of obesity caused by damage to the hypothalamus, resulting in rapid weight gain among other health complications.
The placebo-controlled, double-blind, randomised trial (NCT05774756) met its primary endpoint of reduction in body mass index (BMI) in both adult and paediatric patients versus placebo. In the study, there was a 19.8% placebo-adjusted reduction in BMI, with a 16.5% reduction from baseline for all patients treated with Imcivree compared to a 3.3% BMI increase in patients on placebo. Of the patients treated with Imcivree, 83% achieved a BMI reduction of 5% or greater at 52 weeks.
Rady Children's Hospital-San Diego's paediatric endocrinologist Dr Susan Phillips said: “Acquired hypothalamic obesity is a serious disease resulting from damage to the hypothalamus, often due to brain tumours or their treatment or certain other injuries resulting in accelerated weight gain, hyperphagia and reduction in energy expenditure.
"There is an urgent need for effective treatments as current approaches, including lifestyle interventions and pharmacotherapy intended for general obesity, have shown limited effectiveness in achieving long-term, durable weight loss.”
Clinically meaningful improvements were also observed across key secondary endpoints including a 1.4 placebo-adjusted mean reduction in the weekly average of the daily maximal hunger score for patients 12 years old or older.
No new safety signals were observed in the study, with the therapy remaining generally well-tolerated. The most common treatment-emergent adverse events (AEs) were nausea, vomiting, diarrhoea, injection site reaction, headache and skin hyperpigmentation. No serious AEs leading to study discontinuation were reported.
As a result of the positive topline data, Rhythm is aiming to file for regulatory approval for Imcivree in acquired hypothalamic obesity to both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in Q3 2025.
Imcivree has already gained approval from the FDA in 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. In Europe and the UK, Imcivree is approved for patients aged two and older with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency.