Rhythm Pharmaceuticals Presents New Data from Phase 2 and 3 Trials Evaluating Setmelanotide in Multiple Rare Genetic Diseases of Obesity at the 59th Annual ESPE Meeting

-- New subgroup analysis of Phase 3 data show setmelanotide achieved statistically significant weight loss and hunger reduction compared with placebo at 14 weeks in patients with Bardet-Biedl syndrome ---- Efficacy results from complete topline analyses of Rhythm’s Phase 2 Basket Study show weight loss and hunger reduction at three months on therapy in patients with SRC1 or SH2B1 deficiency ---- Data from Phase 2 Basket Study also show clear separation between responders and non-responders in change in weight for adults and in BMI-Z scores for children and adolescents --

BOSTON, Sept. 22, 2021 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company committed to transforming the care of people living with rare genetic diseases of obesity, today presented new data and analyses from phase 2 and 3 trials evaluating setmelanotide at the 59th Annual European Society for Paediatric Endocrinology (ESPE) Meeting, which is being held virtually this week.

The Company and its collaborators delivered three oral presentations and four poster presentations, including:

• a new subgroup analysis of data from the 52-week, Phase 3 trial evaluating setmelanotide in Bardet-Biedl syndrome (BBS) that showed setmelanotide achieved statistically significant weight loss and hunger reduction compared to minimal effect observed with placebo during a 14-week, double-blind treatment period;
• complete topline analyses from the exploratory Phase 2 Basket Trial that showed setmelanotide achieved clinically meaningful weight loss or BMI-Z reduction in 30% (9 of 30) of study participants with obesity due to variants of the SRC1 gene; and
• complete topline analyses from the exploratory Phase 2 Basket Trial that showed setmelanotide achieved clinically meaningful weight loss or BMI-Z reduction in 43% (15 of 35) of study participants with obesity due to variants of the SH2B1 gene, including 16p11.2 chromosomal deletions.

“We know from decades of study that reduced activation of the central melanocortin-4 receptor (MC4R) pathway can lead to early-onset, severe obesity and a pathological hunger known as hyperphagia, which characterize rare genetic diseases of obesity,” said Dr. Jesús Argente, who is an author on all three oral presentations and Professor in the Department of Pediatrics and Pediatric Endocrinology, Universidad Autónoma de Madrid in Spain. “In these trials, treatment with setmelanotide, an MC4R agonist, provided patients across three distinct diseases – BBS, as well as obesity due to SRC1 or SH2B1 deficiency – with clinically meaningful reductions in weight loss and hunger. Together, these data support the potential for further development of setmelanotide for patients with rare genetic diseases of obesity driven by a range of variants in the MC4R pathway.”

“In addition to presenting data from our Phase 2 and 3 trials of setmelanotide, we also presented posters at ESPE describing the gene selection process and the design of our Phase 2 DAYBREAK trial,” said Linda Shapiro, M.D., Ph.D., Chief Medical Officer of Rhythm. “We are excited to share these presentations, which provide further rationale for our planned clinical development strategy. Collectively, these presentations depict setmelanotide’s potential to deliver meaningful benefit – even without change in exercise or diet -- to people with obesity and variants in the SRC1 or SH2B1 gene, both of which are included in our Phase 3 EMANATE trial, and they support our decision to enroll people with obesity and variants in at least one of 31 other genes, all of which have ‘strong’ or ‘very strong’ MC4R pathway relevance, in our Phase 2 DAYBREAK trial. We look forward to initiating both EMANATE and DAYBREAK in the fourth quarter, which will evaluate setmelanotide on top of standard of care dietary and physical activity guidance, as we work to broaden setmelanotide’s reach to many more patients with rare genetic diseases of obesity caused by variants in the MC4R pathway.”

New Subgroup Analysis of Data from Phase 3 Trial in BBSIn a presentation entitled, “Phase 3 Trial of Setmelanotide in Participants with Bardet-Biedl Syndrome: Placebo-Controlled Results,” Dr. Argente presented data from a 14-week double-blind treatment period, which preceded an open-label period that totaled 52 weeks on therapy. Highlights of the data include:

• Patients 12 years old or older treated with setmelanotide (n=14) compared to placebo (n=15) at 14 weeks demonstrated an average:
  • Greater weight loss of 3.8 kg, or 3%, of their baseline body weight (p