Rhythm Pharmaceuticals announces five presentations at ESPE 2024

Rhythm Pharmaceuticals (RYTM) announced the presentation of new, real-world data that showed four pediatric patients with acquired hypothalamic obesity or congenital hypothalamic obesity achieved greater than5% weight reduction at three months on setmelanotide, a melanocortin-4 receptor agonist. These data were among five Rhythm-related presentations delivered during the 62nd annual meeting of the European Society for Paediatric Endocrinology in Liverpool, England. 3-month real-world setmelanotide hunger and weight outcomes in four French pediatric patients with acquired or congenital hypothalamic obesity: The presentation includes results from four case reports of patients less than18 years old, two with acquired hypothalamic obesity and two with congenital hypothalamic obesity, at month three on setmelanotide therapy: Congenital hypothalamic obesity: Female, age 15, with septo-optic dysplasia as cause of hypothalamic obesity, achieved a body weight decrease of 9.6% from baseline at month 3 and BMI-Z score change from 3.1 at baseline to 2.8; Male, age 9, with pituitary stalk interruption syndrome as cause of hypothalamic obesity, achieved a body weight decrease of 5.2% from baseline at month 3 and BMI-Z score change from 3.7 at baseline to 3.5; Acquired hypothalamic obesity: Male, age 13, with acquired hypothalamic obesity related to craniopharyngioma resected at age 9, achieved a body weight decrease of 5.6% from baseline at month 3 and 9.5% weight reduction at month 6, and BMI-Z score change from 3.7 at baseline to 3.4 at month six of setmelanotide therapy; and Male, age 13, with acquired hypothalamic obesity related to radiotherapy for juvenile pilocytic astrocytoma, achieved a body weight decrease of 8.3% from baseline at month 3 and BMI-Z score change from 3.1 at baseline to 2.8. These patients were treated with setmelanotide at four different hospitals in France under a pre-marketing, early-access authorization program. All four patients remain on therapy, as of November 15, 2024, and there were no new safety signals observed. Also today, Rhythm announced plans for a new, 34-week substudy designed to evaluate setmelanotide in 39 patients with congenital hypothalamic obesity aged 4 years and older. Rhythm is seeking approval from the U.S. Food and Drug Administration for the independent substudy for congenital hypothalamic obesity as a protocol amendment to the Company’s ongoing Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity. Rhythm anticipates enrolling the first patients with congenital hypothalamic obesity in the first quarter of 2025. The substudy in congenital hypothalamic obesity is independent from Rhythm’s pivotal Phase 3 trial in acquired hypothalamic obesity. The Company remains on track to disclose topline data from that pivotal trial in the first half of 2025. In a poster entitled, “Evaluating Setmelanotide Treatment for 12 Months in Pediatric Age Groups With Rare Melanocortin-4 Receptor Pathway-Related Obesity: Efficacy in Weight Reduction and Safety Outcomes,” presenters highlighted the importance of early intervention in young patients with rare MC4R pathway diseases. A cross-sectional analysis of 50 patients aged 2 to 17 years with rare MC4R pathway diseases who participated in one of five different clinical trials of setmelanotide was presented showing that patients regardless of age achieved clinically meaningful weight reductions, and that children between 2 and 5 years old achieved a greater absolute BMI Z reduction. Additionally, the Company delivered three oral presentations based on analyses of more than 5,000 sequencing samples from the Company’s European genetic testing program for individuals with suspected rare MC4R pathway diseases, Rare Obesity Advanced Diagnosis or ROAD. Genetic testing of individuals with early-onset obesity can help improve disease etiology understanding and identify patients who may benefit from specialized care. Highlights from these three presentations included: 1.74% of individuals tested carried a biallelic variant in one of 22 tested genes related to Bardet-Biedl syndrome and the frequency in Turkey was 5.82%, potentially due to consanguinity rates; 22.5% of tested individuals with early-onset obesity carried a variant classified as pathogenic, likely pathogenic or of unknown significance of one or more genes closely associated with MC4R pathway function: SIM1, SEMA3 family, PLXNA family, POMC, PCSK1, LEPR, SH2B1 and NCOA1; and 4.9% of tested individuals carried a biallelic or heterozygous pathogenic, likely pathogenic or VUS variant in one or more of these genes: ALMS1, BBS, MAGEL2, PHIP, or TBX3 genes. These genes are associated with certain debilitating syndromes.