Rhythm Pharmaceuticals Announces Publication of Results from Phase 3 Clinical Trial of IMCIVREE (setmelanotide) in Bardet-Biedl Syndrome

Rhythm Pharmaceuticals, Inc. recently announced that previously disclosed results from a Phase 3 clinical trial that evaluated IMCIVREE (setmelanotide), an MC4R agonist, in patients with Bardet-Biedl syndrome (BBS) have been published in the peer-reviewed journal The Lancet Diabetes and Endocrinology. The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.

“Hyperphagia, which is a pathological hunger, and early-onset, severe obesity place a significant burden on both patients living with BBS and their families,” said Prof. Andrea M. Haqq, MD, Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta. “The results from this pivotal Phase 3 clinical trial – the largest and longest interventional study ever conducted in BBS – showed patients with BBS achieved clinically significant weight loss, reductions in hunger and improvements in health-related quality of life, all of which are highly meaningful to patients with BBS and their caregivers.”

Based on these pivotal Phase 3 data, IMCIVREE was approved as the first therapy for chronic weight management in adult and pediatric patients 6 years of age and older with BBS in the US and European Union (EU). BBS is a rare genetic disease that affects approximately 1,500-2,500 people in the US and 2,500 people in the EU and UK. People living with BBS may experience insatiable hunger, also known as hyperphagia, and severe obesity beginning early in life. BBS may also be associated with cognitive impairment, polydactyly, renal dysfunction, hypogonadism and visual impairment.

Rhythm’s multicenter Phase 3 trial (NCT03746522) enrolled patients ≥6 years old with obesity and BBS or Alström syndrome (N=38). Patients were randomized 1:1 to receive up to 3mg of daily subcutaneous setmelanotide or placebo in a 14-week double-blind period, followed by open-label setmelanotide for 52 weeks of treatment total. The primary endpoint was the proportion of patients ≥12 years old in the full analysis set achieving ≥10% weight reduction after 52 weeks. Hunger and safety were also assessed.

As previously disclosed, treatment with setmelanotide resulted in significant weight and hunger reductions after one year of treatment among patients with BBS. The primary endpoint was achieved by 32.3% (95% confidence interval (CI), 16.7%, 51.4%; p=0.0006) of patients ≥12 years old, all of whom were patients with BBS. None of the responders were patients with Alström syndrome.

Data highlights among patients with BBS (n=32) after 52 weeks of setmelanotide include:

• Fifteen (15) patients ≥18 years achieved a mean (SD) percent reduction in BMI of -9.1% (6.8%; 95% CI, −13.4%, −4.8%);
• Fourteen (14) patients <18 years achieved a mean (SD) change in BMI Z score of −0.8 (0.5; 95% CI, −1.0, −0.5), and 12 patients (85.7%) achieved ≥0.2-point reduction in BMI Z; and
• Fourteen (14) patients ≥12 years who reported hunger scores achieved reduction of -30.5% in maximal hunger score.

The safety profile observed in this study was consistent with that observed with setmelanotide in previous clinical trials in patients with other rare MC4R pathway diseases. Skin hyperpigmentation (n=23; 60.5%) was the most common adverse event (AE). Two patients experienced serious AEs, neither of which was considered related to setmelanotide treatment.

“With early, significant and sustained weight reduction demonstrated in our Phase 3 trial, we were able to secure approvals in the United States and European Union and deliver the first treatment for obesity in patients with BBS,” said David Meeker, MD, Chair, President and Chief Executive Officer of Rhythm. “We look forward to leveraging the publication of these trial results to drive continued momentum, as we work toward our goal of bringing a new option to people who are living with this rare genetic disease around the world, while also targeting additional rare MC4R pathway diseases with our broad ongoing clinical development program.”

Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases. Rhythm’s precision medicine, setmelanotide, is approved by the US FDA for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). The European Commission (EC) has authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. The UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare genetic diseases of obesity and is leveraging the Rhythm Engine and the largest known obesity DNA database — now with approximately 45,000 sequencing samples — to improve the understanding, diagnosis and care of people living with severe obesity due to certain genetic deficiencies. Rhythm’s headquarters is in Boston, MA.