Imcivree (setmelanotide) / Rhythm Pharma - LARVOL DELTA

Resolution of chronic idiopathic urticaria with setmelanotide in a patient with Bardet-Biedl Syndrome: A case report. (PubMed, Obes Pillars) - "Adjunct phentermine 18.75 mg daily was later added to optimize appetite control. Setmelanotide produced durable remission of refractory CIU in a patient with BBS, suggesting MC4R agonism may exert immunomodulatory effects beyond weight regulation. This finding underscores the broader potential of precision therapies for rare obesity syndromes to reveal new mechanisms of inflammation control."

Journal • Bardet–Biedl Syndrome • Chronic Spontaneous Urticaria • Dermatology • Developmental Disorders • Genetic Disorders • Immunology • Inflammation • Inherited Retinal Dystrophy • Obesity • Ophthalmology • Renal Disease • Urticaria • BBS9 • MC4R

Efficacy of Semaglutide in Pediatric Patients With Bardet-Biedl Syndrome and Alström Syndrome. (PubMed, JCEM Case Rep) - "While setmelanotide, a melanocortin-4 receptor agonist, may be an effective therapy for obesity in these conditions (especially BBS), its cost limits accessibility for many patients. We describe two pediatric cases (one with BBS and another with AS) demonstrating significant metabolic improvements with semaglutide, a glucagon-like peptide-1 receptor agonist. These observations suggest that some cases of BBS and AS may be treated with semaglutide."

Journal • Alstrom Syndrome • Bardet–Biedl Syndrome • Genetic Disorders • Inherited Retinal Dystrophy • Obesity • Ophthalmology • Pediatrics • LEP

Survey of Drugs Induced Skin Pigmentation (Hyper and Hypo Pigmentation). (PubMed, Clin Cosmet Investig Dermatol) - "Minocycline (ROR 115.66) and setmelanotide (ROR 1506.82) showed high RORs for hyperpigmentation, while triamcinolone (ROR 37.20) and ribociclib (ROR 60.20) were strongly linked to hypopigmentation. Several drugs, including dupilumab, tretinoin, and clobetasol, exhibited bidirectional pigmentary modulation...These findings emphasize the importance of early recognition and dermatologic monitoring during prolonged therapy. Considering the odds ratio and analysis results, the drugs found to be associated with hyperpigmentation or hypopigmentation warrant further investigation."

Journal

Cardiometabolic Results From a Phase 3 Trial of Setmelanotide in Acquired Hypothalamic Obesity (Rhythm Press Release) - "Jennifer Miller, M.D., University of Florida Division of Endocrinology, Department of Pediatrics in the College of Medicine, was the lead author on a poster that showed setmelanotide treatment was associated with significant improvement across most cardiometabolic parameters and proteomic biomarkers. Results showed improvements across nonambulatory blood pressure, lipid levels, and hematologic and chemistry parameters."

P3 data • Hypothalamic Injury-associated Obesity

Dr. Roth delivered an oral presentation detailing previously disclosed results from a post-hoc analysis of Phase 3 TRANSCEND data of setmelanotide in patients with acquired hypothalamic obesity who received concomitant GLP-1 therapy during the trial. (Rhythm Press Release) - "-27.1% (p<0.0001) mean placebo-adjusted difference in BMI reduction in patients (n=9) treated with setmelanotide and GLP-1 therapy concurrently compared with GLP-1 therapy and placebo (n=6); and -19.0% (p<0.0001) mean placebo-adjusted difference in BMI reduction in patients treated with setmelanotide (n=72) compared with placebo (n=33); none of these patients were on GLP-1 therapy during the trial....The results from interviews with 14 trial participants and 16 caregivers of trial participants younger than 12 showed that patients consistently reported meaningful and beneficial changes in hunger, weight, energy levels, and physical activity with setmelanotide therapy."

P3 data • Hypothalamic Injury-associated Obesity

Efficacy of Setmelanotide in Patients With Acquired HO Previously or Concurrently on GLP 1 Therapy (OBESITY WEEK 2025) - P3 | "The response to setmelanotide observed in pts receiving prior and/or concurrent GLP1-RAs highlights the improved benefit of other pharmacologic interventions once the deficit in MC4R signaling has been corrected. These data add to the available evidence demonstrating that setmelanotide represents a promising treatment option for patients with aHO aged ≥4 y."

Clinical • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity • MC4R

Case Report: Setmelanotide and Urticaria Resolution in Bardet-Biedl Syndrome (OBESITY WEEK 2025) - "She also had a history of chronic idiopathic urticaria (CIU) resistant to dual antihistamine therapy, necessitating daily use of diphenhydramine and cetirizine. This case demonstrates the resolution of chronic idiopathic urticaria with the use of setmelanotide in a patient diagnosed with BBS. BBS is primarily caused by mutations in genes essential for ciliary function, leading to impaired cellular signaling pathways, particularly those involved in development and metabolism. This dysfunction results in a range of clinical manifestations due to disrupted intercellular communication, but is not typically associated with inflammatory or dermatologic conditions."

Case report • Clinical • Bardet–Biedl Syndrome • Chronic Spontaneous Urticaria • Dermatology • Genetic Disorders • Immunology • Inherited Retinal Dystrophy • Obesity • Ophthalmology • Urticaria • BBS9 • KIDINS220

Cardiometabolic Results From a Phase 3 Trial of Setmelanotide in Acquired Hypothalamic Obesity (OBESITY WEEK 2025) - P3 | "Setmelanotide treatment was associated with a significant improvement in cardiometabolic parameters, underscoring the broadly encompassing benefits and impacts of setmelanotide treatment on metabolic health. These cardiometabolic data add to the available evidence of robust, clinically significant, and consistent response to setmelanotide treatment in patients with aHO, suggesting the promising potential of setmelanotide as a treatment option for this patient population."

P3 data • Cardiovascular • Genetic Disorders • Hypothalamic Injury-associated Obesity • Metabolic Disorders • Obesity • LEP

Patient- and Caregiver-Reported Experience With Acquired Hypothalamic Obesity in the TRANSCEND Trial (OBESITY WEEK 2025) - P3 | "This substudy confirms the positive treatment benefits and meaningfulness of improvements associated with setmelanotide in patients with aHO. These results are highly supportive of the Phase 3 TRANSCEND efficacy outcomes seen with setmelanotide."

Clinical • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

Frequency of Genetic Variants Associated With Obesity Among Patients Pursuing Weight Loss Treatment (OBESITY WEEK 2025) - "While monogenic gene variants associated with obesity are rare, identifying these mutations is increasingly justified due to the development of mutation-specific therapies such as setmelanotide, a melanocortin-4 receptor (MC4R) agonist... As there continues to be significant variations in response to clinical treatments for obesity, our findings suggest that genetic testing can provide insight to potential targeted therapies for many patients, possibly improving treatment outcomes."

Clinical • Bardet–Biedl Syndrome • Genetic Disorders • Inherited Retinal Dystrophy • Leptin Receptor Deficiency Obesity • Obesity • Ophthalmology • CEP290 • LEP • PCSK1 • PLXNA1

Craniopharyngioma - What's next. (PubMed, Pituitary) - "Therapeutic interventions such as dextroamphetamine and other centrally acting stimulants, along with glucagon-like peptide-1 receptor (GLP-1R) agonists, and setmelanotide have shown potential in promoting weight reduction. Bariatric surgery has also demonstrated efficacy; however, the use of irreversible surgical techniques in pediatric populations remains ethically and legally contentious. This report summarizes perspectives of future research and clinical progress in diagnostics, treatment, and follow-up of patients with craniopharyngioma."

Journal • Brain Cancer • Cardiovascular • CNS Tumor • Genetic Disorders • Hypothalamic Injury-associated Obesity • Metabolic Disorders • Obesity • Oncology • Pediatrics

Rhythm Pharmaceuticals Announces FDA Extension of Review Period for IMCIVREE (setmelanotide) for Patients with Acquired Hypothalamic Obesity (GlobeNewswire) - "On Nov. 6, the FDA notified the Company that the Prescription Drug User Fee Act (PDUFA) goal date has been extended from December 20, 2025 to March 20, 2026. The FDA in October requested additional sensitivity analyses of clinical efficacy data from Rhythm’s Phase 3 pivotal trial in acquired hypothalamic obesity. No new data were requested. The additional information has been deemed a ‘major amendment,’ which allows for additional time for the FDA to review."

PDUFA • Hypothalamic Injury-associated Obesity

Rhythm Pharmaceuticals Announces Public Reimbursement for IMCIVREE (setmelanotide) in Canada in Five Provinces and Under the Federal Non-Insured Health Benefits Program (GlobeNewswire) - "IMCIVREE now publicly covered for weight management due to Bardet-Biedl syndrome (BBS) in Ontario, Alberta, British Columbia, Saskatchewan, Nova Scotia and under NIHB."

Reimbursement • Bardet–Biedl Syndrome • Obesity

Today, Rhythm announced that four abstracts have been accepted for presentation – one oral presentation and three posters – at the Obesity Society’s Annual Meeting at ObesityWeek 2025 this week in Atlanta, GA (GlobeNewswire)

Clinical data • Hypothalamic Injury-associated Obesity

Anticipated Upcoming Milestones (GlobeNewswire) - "Receive a decision from the FDA on our sNDA (anticipated to be received by the PDUFA goal date of December 20, 2025) for setmelanotide in conditions associated with acquired hypothalamic obesity; Complete enrollment in the Phase 1, Part C trial evaluating the weekly, MC4R agonist RM-718 in patients with acquired hypothalamic obesity in the first quarter of 2026; Announce topline data in the 12-patient Japanese cohort of the setmelanotide Phase 3 trial in acquired hypothalamic obesity in the first quarter of 2026; Announce topline data in the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases in the first quarter of 2026; Complete enrollment in the setmelanotide Phase 3 trial substudy in congenital hypothalamic obesity in the first half of 2026; and Pending further feedback from U.S. and European regulatory agencies, initiate a pivotal Phase 3 trial evaluating bivamelagon in acquired hypothalamic obesity in 2026."

Clinical data • New P3 trial • PDUFA • Trial status • Hypothalamic Injury-associated Obesity • Obesity

Rhythm Pharmaceuticals Reports Third Quarter 2025 Financial Results and Business Update (GlobeNewswire) - "Revenue from global sales of IMCIVREE (setmelanotide) was $51.3 million for the third quarter of 2025. This marks an increase of 6% on a sequential basis from the second quarter of 2025, primarily driven by growth in patients and sales of IMCIVREE for the treatment of patients with BBS. In the third quarter of 2025, revenue of $38.2 million, or 74% of product revenue, was generated in the United States, an increase of 19% on a sequential basis."

Sales • Obesity

Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration. (PubMed, JAMA Ophthalmol) - "Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion. In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Genetic Disorders • Macular Degeneration • Metabolic Disorders • Obesity • Ophthalmology • Retinal Disorders

Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Cataract Development. (PubMed, Am J Ophthalmol) - "GLP-1RA use was associated with a significantly reduced risk of age-related cataract compared to OWLD use and no pharmacologic treatment. These findings support the need for randomized prospective trials and mechanistic studies to better understand this observed association."

Journal • Cataract • Genetic Disorders • Metabolic Disorders • Obesity • Ophthalmology

A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756) (clinicaltrials.gov) - P3 | N=39 | Recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | Trial completion date: Jan 2027 ➔ Sep 2027 | Trial primary completion date: Jan 2027 ➔ Sep 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

A Study of Setmelanotide in Patients With Prader-Willi Syndrome (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | Trial completion date: Jan 2026 ➔ Oct 2027 | Trial primary completion date: Jan 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Obesity • Prader–Willi syndrome

Case Report: Improvement in cognitive functioning following setmelanotide initiation in a patient with Bardet-Biedl syndrome. (PubMed, Front Endocrinol (Lausanne)) - "One month following treatment initiation, the patient not only endorsed reduced appetite, but also demonstrated a significant improvement in cognitive and affective functioning, as noted in her mental status exam and her performance on the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) tests, when compared to results prior to starting setmelanotide. Although previous studies have reported improved quality of life measures in patients with BBS following setmelanotide initiation, this is the first report of improved cognitive and affective functioning following initiation of the medication, highlighting the need to assess the effects of setmelanotide beyond the metabolic domain in patients with BBS."

Journal • Bardet–Biedl Syndrome • Diabetes • Genetic Disorders • Inherited Retinal Dystrophy • Metabolic Disorders • Obesity • Ophthalmology • Type 2 Diabetes Mellitus • LEP

Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases. (PubMed, Diseases) - "Among them, α-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Atopic Dermatitis • CNS Disorders • Depression • Dermatitis • Dermatology • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Major Depressive Disorder • Melanoma • Metabolic Disorders • Multiple Sclerosis • Obesity • Ocular Inflammation • Oncology • Ophthalmology • POMC-null Obesity • Psychiatry • Reperfusion Injury • Respiratory Diseases • Rheumatology • Sarcoidosis • Scleroderma • Sexual Disorders • Solid Tumor • Systemic Sclerosis • Type 2 Diabetes Mellitus • Uveitis • LEP • LEPR

Pharmacotherapy for Obesity: Recent Updates. (PubMed, Clin Pharmacol) - "We start by focusing on the non-incretin anti-obesity medications orlistat, phentermine, phentermine-topiramate, and naltrexone-bupropion. We also highlight setmelanotide for heritable obesity. The mechanism of action and comparative efficacy of the GLP-1 receptor agonists liraglutide and semaglutide are reviewed...Additional incretin targets in the pipeline include dual co-agonists to glucagon and GLP-1 receptors, triple agonists targeting glucagon, GLP-1 and GIP, novel GLP-1 agonists, oral formulations of GLP-1 agonists, and amylin agonists. Finally, we provide best practices for adjuncts to pharmacologic treatments of obesity, monitoring efficacy of obesity treatments, and adjusting medication regimens for providers."

Journal • Review • Genetic Disorders • Obesity

Late Breaking Abstract - Obstructive sleep apnoea in Bardet-Biedl syndrome (ERS 2025) - "OSA is common in children with BBS, underscoring the need for routine sleep assessment and diagnostics. Those with severe obesity or specific genotypes may be at higher risk. Setmelanotide offers a potential alternative to surgery or NIV, with promise in reducing long-term disease burden."

Late-breaking abstract • Bardet–Biedl Syndrome • Cardiovascular • Inherited Retinal Dystrophy • Obesity • Obstructive Sleep Apnea • Ophthalmology • Pediatrics • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Leptin and Leptin Resistance in Obesity: Current Evidence, Mechanisms and Future Directions. (PubMed, Endocr Connect) - "Alternative strategies, such as melanocortin-4 receptor (MC4R) agonists (e.g., setmelanotide) for LRD treatment, are very promising. Future directions include enhancing leptin sensitization, combining leptin with other drugs, and exploring partial leptin reduction to mitigate compensatory responses during weight loss. The review emphasizes the complexity of leptin resistance and the necessity of targeted approaches in obesity therapy."

Journal • Genetic Disorders • Inflammation • Leptin Receptor Deficiency Obesity • Lipodystrophy • Metabolic Disorders • Obesity • LEP • LEPR