Rhythm(RYTM)2025-02-26 12:02Financial Performance - Preliminary unaudited net revenues from global sales of IMCIVREE were approximately 130 million for FY 2024, representing a 26% quarter-over-quarter increase from Q3 2024[8][10]. - 74% of Q4 2024 revenues and 73% of FY 2024 revenues were generated from the U.S. market[10]. - The company plans to report fourth quarter and full year 2024 financial results in late February 2025[10]. Clinical Trials and Development - The ongoing Phase 3 trial for setmelanotide in acquired hypothalamic obesity is expected to report topline data in H1 2025[8][21]. - Enrollment in the supplemental Japanese cohort of the Phase 3 trial for setmelanotide has been completed[8]. - Rhythm Pharmaceuticals is advancing clinical development for setmelanotide in Prader-Willi syndrome and genetically-defined MC4R pathway diseases[6][8]. - The company is driving life-cycle management with bivamelagon and RM-718, with plans to initiate a new Phase 2 trial for setmelanotide in Prader-Willi syndrome in Q1 2025[6][8][21]. - Rhythm Pharmaceuticals has completed enrollment in two substudies in the Phase 3 EMANATE trial for genetically-caused MC4R pathway diseases[8]. - The Phase 3 Hypothalamic Obesity Trial has completed enrollment, with data expected in H1 2025[51]. - Enrollment for the Phase 3 EMANATE trial was completed in Q4 2024, with topline data expected in H1 2026[78]. - The ongoing SIGNAL trial is a 14-week Phase 2 open-label trial evaluating Bivamelagon in patients with hypothalamic obesity, with enrollment expected to complete in Q1 2025[68]. - A 34-week substudy in congenital hypothalamic obesity is expected to begin enrollment in Q1 2025, leveraging the existing Phase 3 trial infrastructure[61]. - The company plans to initiate an exploratory Phase 2 trial of setmelanotide for Prader-Willi syndrome (PWS) in Q1 2025, targeting up to 20 patients aged 6 to 65 years[92]. Treatment Efficacy - Setmelanotide achieved a mean percent reduction in BMI of -17.7% from baseline at Month 12[37]. - All patients in the study experienced a decrease in obesity severity, with three out of eleven pediatric patients achieving normal weight at one year[42]. - In a real-world study, the mean BMI reduction was -5.6% at Month 1 and -12.8% at Month 3 for adult patients with acquired hypothalamic obesity[49]. - In the DAYBREAK Phase 2 trial, a mean BMI change of -12.4% was observed from baseline among 32 patients on continuous setmelanotide therapy, with 84% achieving or maintaining a >5% BMI reduction[85]. - The DAYBREAK trial's primary endpoint is the proportion of patients achieving a BMI reduction of ≥5% from baseline in response to setmelanotide at the end of Stage 1[81]. - The company reported that 27 out of 32 patients on setmelanotide achieved or maintained a >5% BMI reduction, with a p-value of 0.001 indicating statistical significance[85]. - The pediatric baseline BMI for participants in the DAYBREAK trial was recorded at 2.5 (SD: 0.3), with a range of 1.83 to 2.97[82]. - The company reported positive real-world data from a French early-access program, indicating Setmelanotide may be an effective treatment for congenital hypothalamic obesity[55]. Market Potential and Unmet Needs - The estimated U.S. prevalence of hypothalamic obesity is approximately 29,000 patients, with a significant unmet medical need[17][27]. - The EMANATE trial aims to address a potential market of over 6,000 patients with heterozygous POMC/PCSK1 deficiency and 4,000 with heterozygous LEPR deficiency[76]. - Setmelanotide is being developed for congenital hypothalamic obesity, which has no approved therapies and an estimated prevalence of over 1,000 patients in the U.S. and Europe[54]. - The U.S. prevalence of Bardet-Biedl syndrome (BBS) is estimated to be between 4,000 and 5,000 patients, with a similar number in Europe[101]. - IMCIVREE, the first FDA- and EMA-approved therapy for BBS, has shown steady growth in net product revenues since its launch, reaching 298.4 million as of September 30, 2024, to fund operations into 2026[19]. - The company is actively expanding its market presence in the U.S. and Europe, with ongoing patient identification efforts and genetic sequencing data to support its initiatives[101].