Rhythm Pharmaceuticals Presents New Data from Phase 3 Trial Evaluating Setmelanotide in Patients with Bardet-Biedl Syndrome

Rhythm Pharmaceuticals, Inc. recently announced the presentation of new data supporting the potential for setmelanotide to treat the early onset obesity, hyperphagia, and metabolic impairment associated with Bardet-Biedl syndrome (BBS). In addition, the company announced cumulative safety data from across the setmelanotide clinical development program. These data were presented at the Pediatric Endocrine Society (PES) 2022 Virtual Annual Meeting, held April 28-May 1.

The company and its collaborators delivered one oral presentation and three e-poster presentations, including:

• New data from the 52-week Phase 3 trial evaluating setmelanotide in patients with BBS, which demonstrate that setmelanotide improved body weight measures, as well as total HDL and LDL cholesterol and triglyceride levels, with no changes in blood pressure or heart rate;
• New data from the 52-week Phase 3 trial specific to adolescents and children with BBS, which show that setmelanotide treatment was associated with clinically meaningful reductions in body mass index (BMI), BMI-Z scores, and percent of the 95^th BMI percentile (%BMI₉₅);
• New results from a study based on in-depth interviews conducted with BBS patients and caregivers enrolled in either Rhythm’s Phase 2 Basket Trial or Phase 3 BBS pivotal trial, which suggest that setmelanotide treatment reduced patients’ hyperphagia, body weight, and obsessive focus on food, resulting in substantially improved general health and emotional well-being; and
• Cumulative safety data from across 561 participants treated in Rhythm’s 16 Phase 1, 2, or 3 clinical trials of setmelanotide in healthy volunteers and people with obesity due to rare genetic variants, which demonstrate that setmelanotide was generally well tolerated.

“The new data presented at PES reinforce setmelanotide’s potential to be a safe and effective precision therapy, which can deliver meaningful benefit to people living with BBS, reducing hyperphagia, weight, and comorbid factors of the metabolic syndrome, while also improving emotional well-being,” said Linda Shapiro, MD, PhD, Chief Medical Officer of Rhythm. “As we prepare for a potential US approval in BBS later this quarter, we are encouraged by these new data and look forward to sharing them with the health care community, as we continue efforts to educate about BBS, the patient and caregiver experience, and the need for treatment.”

Andrea Haqq, MD, MHS, Professor, Department of Pediatrics, Division of Pediatric Endocrinology/Metabolism at the University of Alberta, delivered an oral presentation titled, Impact of Setmelanotide Treatment on Lipid Parameters and Vital Signs in Patients with Bardet-Biedl Syndrome in a Phase 3 Trial.

“Due to their early onset, severe obesity and hyperphagia, people living with BBS are at a high risk of comorbid metabolic syndrome,” said Dr. Haqq. “The data presented at PES suggest for the first time that the benefits of setmelanotide treatment go beyond weight and hunger reduction, affecting lipid parameters that are known to play important roles in increasing the likelihood that patients develop ischemic heart disease, stroke, and chronic kidney disease. These results highlight the potential for setmelanotide to address the major health ramifications associated with rare genetic diseases of obesity, and further support its advancement as a precision therapy for BBS.”

The pivotal Phase 3 trial included 31 response-evaluable patients aged 7 years old or older with BBS. Patients’ fasting lipid profiles were assessed before study initiation and after 52 weeks of therapy; weight and vital signs were assessed throughout the trial. As previously disclosed, data from this Phase 3 trial show that treatment with setmelanotide was associated with significant reductions in body weight and hunger.

This presentation included new data specific to patients’ lipid parameters and vital signs. Following one year of setmelanotide treatment, the mean percent changes in total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were -6.1%, 5.3%, -7.8% and -9.6%, respectively. No systematic changes in blood pressure or heart rate were identified.

Robert Haws, MD, Marshfield Clinic Research Institute, presented an e-poster titled, Setmelanotide Treatment in Pediatric and Adolescent Patients with Bardet-Biedl Syndrome and Severe Obesity, which provided additional data specific to adolescents and children enrolled in Rhythm’s Phase 3 clinical trial. As previously disclosed, patients younger than 18 years of age with BBS (n=16) had a mean reduction in BMI-Z score of 0.8.

This presentation included new data specific to patients’ BMI and %BMI₉₅, which show that pediatric patients with BBS had a mean reduction in BMI of -3.36kg/m² (-9.50%) and a mean change in %BMI₉₅ of -17.3.

In an e-poster entitled, Patient and Caregiver-Reported Experiences of Hyperphagia in Bardet-Biedl Syndrome Before and During Setmelanotide Treatment, Claire Ervin, MPH, Senior Director, Patient-Centered Outcomes Assessment at RTI Health Solutions, presented qualitative data from 19 interviews conducted with BBS patients and caregivers who participated in Rhythm’s Phase 2 Basket Trial and Phase 3 BBS pivotal trial.

Prior to setmelanotide treatment, all participants described their hunger, or their child’s hunger, as all-consuming, and noted a negative impact on daily life, including difficulties with concentration, decrements in emotional and physical well-being and impaired relationships. All participants experienced or observed notable reductions in hunger during treatment with setmelanotide. This led to a decrease in food-seeking behaviors, weight loss, and better health. All participants reported improvements in how they felt – physically and/or emotionally – and generally reported high levels of satisfaction with treatment.

Jesús Argente, MD, PhD, Professor in the Department of Pediatrics and Pediatric Endocrinology, Universidad Autónoma de Madrid in Spain, presented an e-poster titled, Clinical Safety Summary of Setmelanotide in Healthy Volunteers with Obesity and Patients with Rare Genetic Diseases of Obesity, which detailed safety data from across 16 Phase 1, 2 or 3 clinical trials of setmelanotide.

As of March 8, 2021, 561 people, including 228 otherwise healthy volunteers with obesity and 308 patients with rare genetic diseases of obesity, had received at least one dose of setmelanotide, with 24% of patients receiving treatment for at least six months and 17% of patients for one year. Data suggest that setmelanotide was generally well tolerated, with a mostly consistent safety profile across age, sex, ethnicity, race, and clinical diagnosis.

All Rhythm’s presentations from PES will be available on the Publications and Presentations section of its website: https://www.rhythmtx.com/publications/.

Rhythm is a commercial-stage biopharmaceutical company committed to transforming the treatment paradigm for people living with rare genetic diseases of obesity. Rhythm’s precision medicine, IMCIVREE (setmelanotide), was approved in November 2020 by the US FDA for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to POMC, PCSK1 or LEPR deficiency confirmed by genetic testing and in July and September 2021, respectively, by the European Commission (EC) and Great Britain’s Medicines & Healthcare Products Regulatory Agency (MHRA) 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. IMCIVREE is the first-ever FDA-approved and EC- and MHRA-authorized therapy for patients with these rare genetic diseases of obesity. The company submitted a supplemental New Drug Application (sNDA) to the FDA, which was accepted for filing in November 2021 and is currently assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 16, 2022, for the treatment of obesity and control of hunger in adult and pediatric patients six years of age and older with Bardet-Biedl Syndrome (BBS) or Alström syndrome. A Type II variation application to the European Medicines Agency seeking regulatory approval and authorization for setmelanotide to treat obesity and control of hunger in adult and pediatric patients 6 years of age and older with BBS also is under review. 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.