Rhythm's Imcivree Shows Significant Weight Loss in Patients with Hypothalamic Obesity
• Rhythm Pharmaceuticals' setmelanotide (Imcivree) demonstrated a 16.5% reduction in body weight compared to a 3.3% gain with placebo in patients with hypothalamic obesity over 52 weeks of treatment.
• The Phase 3 TRANSCEND trial results position Imcivree to potentially become the first approved therapy for obesity caused by brain injury, with regulatory submissions planned for Q3 2025.
• Imcivree works by targeting the melanocortin-4 receptor pathway, differentiating it from GLP-1 obesity drugs like Wegovy and Zepbound, and expanding Rhythm's presence in specialized obesity treatment markets.
Rhythm Pharmaceuticals Regains Global Control of IMCIVREE by Reacquiring Rights in China
• Rhythm Pharmaceuticals has terminated its 2021 licensing agreement with RareStone Group Ltd., reacquiring rights to IMCIVREE (setmelanotide) in mainland China, Hong Kong, and Macau for $6.3 million.
• The reacquisition aligns with Rhythm's global strategy as the company prepares for topline data readout from its Phase 3 trial in acquired hypothalamic obesity in Q2 2025, with studies conducted across North America, Europe, and Japan.
• IMCIVREE, an MC4R agonist, is currently approved in the US and Europe for treating obesity in patients with specific genetic conditions including Bardet-Biedl syndrome and certain genetic deficiencies.
Setmelanotide Receives Orphan Drug Designation in Japan for Hypothalamic Obesity Treatment
• Rhythm Pharmaceuticals' setmelanotide has received orphan drug designation from Japan's Ministry of Health for the treatment of acquired hypothalamic obesity, a rare condition affecting an estimated 5,000-8,000 patients in Japan.
• Setmelanotide, a melanocortin-4 receptor agonist, is currently being evaluated in a global Phase 3 trial with topline data expected in Q2 2025, potentially offering the first therapy targeting the underlying biology of this disease.
• The designation follows similar status in Europe, strengthening Rhythm's global strategy to address significant unmet medical needs for patients with hypothalamic obesity caused by brain tumors, traumatic injury, stroke, or inflammation.
Rhythm Pharmaceuticals Announces Positive IMCIVREE® Sales and Pipeline Advancements
• Rhythm Pharmaceuticals reports preliminary unaudited net revenues of approximately $42 million for Q4 2024 and $130 million for full year 2024 from global IMCIVREE® sales.
• Topline data from the Phase 3 trial of setmelanotide in acquired hypothalamic obesity (HO) is expected in the first half of 2025.
• A new Phase 2 trial exploring setmelanotide in Prader-Willi syndrome (PWS) is planned to commence in the first quarter of 2025.
• Enrollment is completed in the Phase 3 EMANATE trial substudies for genetically-caused MC4R pathway diseases, with topline data anticipated in H1 2026.
Jefferies Initiates Coverage on Rhythm Pharmaceuticals with Bullish Outlook on Obesity Drug Pipeline
Jefferies has initiated coverage of Rhythm Pharmaceuticals with a Buy rating and an $80 price target, citing strong potential in the hypothalamic obesity market. The firm projects potential peak sales growth from $500M to $3B, with particular optimism around the company's second-generation drugs that have patent protection extending into the 2040s.
Novo Nordisk's Cagrilintide/Semaglutide Combo Shows Superior Weight Loss in Phase III Trial
• A fixed-dose combination of cagrilintide and semaglutide led to greater weight loss at 68 weeks compared to either drug alone or placebo in the REDEFINE 1 trial.
• The FDA expanded the indication for setmelanotide (Imcivree) to include children as young as 2 years with specific types of genetic obesity.
• Palatin Technologies reported that 71% of patients with type 2 diabetic nephropathy achieved a significant reduction in urine protein in a phase IIb study with bremelanotide.
FDA Expands Setmelanotide Approval to Include Children Aged 2-5 with Rare Obesity Forms
• The FDA has expanded the approval of setmelanotide (Imcivree) to include children aged 2 to 5 years with rare genetic forms of obesity.
• The expanded indication is based on the VENTURE phase 3 trial, which demonstrated significant BMI reduction in young children with POMC, LEPR deficiencies, and Bardet-Biedl syndrome.
• Setmelanotide is the first precision medicine to target the MC4R pathway, addressing the root cause of hyperphagia and obesity in these rare genetic conditions.
• The most common adverse events observed in clinical trials were mild to moderate, including skin hyperpigmentation and injection site reactions.
FDA Gears Up for Year-End Decisions on Novel Therapies for Rare Diseases and Cancer
• The FDA is set to decide on Ionis Pharmaceuticals' olezarsen for familial chylomicronemia syndrome (FCS), a rare genetic disease, by December 19, following positive Phase III results.
• Lexicon Pharmaceuticals awaits the FDA's decision on sotagliflozin as an adjunct therapy for type 1 diabetes by December 20, despite concerns raised by an advisory committee.
• AstraZeneca and Daiichi Sankyo's Dato-DXd for non-squamous NSCLC is under FDA review, with a decision expected by December 20, based on Phase III data showing progression-free survival benefits.
• Neurocrine Biosciences anticipates FDA decisions on crinecerfont for congenital adrenal hyperplasia (CAH) by December 29 and 30, potentially marking the first new treatment in 70 years.
Lisocabtagene Maraleucel Shows Promise in Relapsed/Refractory Lymphomas
• Lisocabtagene maraleucel (liso-cel) demonstrates efficacy and safety in second-line treatment of relapsed/refractory large B-cell lymphoma (LBCL), aligning with pivotal trial outcomes.
• The TRANSCEND FL trial indicates liso-cel achieved a significant overall response rate in relapsed/refractory marginal zone lymphoma (MZL), meeting the primary endpoint.
• Five-year data from TRANSCEND-NHL-001 underscore the curative potential of liso-cel in third-line LBCL, showing a 38% overall survival rate.
• Real-world data supports liso-cel's effectiveness across diverse LBCL patient subgroups, reinforcing its role as a standard-of-care treatment option.
Setmelanotide Shows Promise in Reducing Obesity in Young Children with Rare Genetic Deficiencies
• A Phase 3 trial of setmelanotide in children aged 2-5 with BBS, POMC, PCSK1, or LEPR deficiency demonstrated clinically meaningful reductions in BMI Z-score.
• 83% of patients achieved a ≥0.2-point reduction in BMI Z-score after 52 weeks of treatment with setmelanotide, indicating significant weight management benefits.
• Caregivers reported a 91% reduction in patient hunger compared to baseline, alongside a reduced sense of personal burden, highlighting improved quality of life.
• Setmelanotide was generally well-tolerated, with no new safety signals, supporting its potential as a targeted therapy for early-onset obesity in this population.
Setmelanotide Shows Promise in Reducing Obesity in Young Children With Rare Genetic Deficiencies
• A Phase 3 trial of setmelanotide in children aged 2-5 years with Bardet-Biedl syndrome or POMC, PCSK1, or LEPR deficiency demonstrated clinically meaningful reductions in BMI Z-score.
• 83% of patients achieved a ≥0.2-point reduction in BMI Z-score after 52 weeks, with a mean percent change in BMI from baseline of -18%.
• Caregivers reported a 91% reduction in patient hunger compared to baseline, alongside a reduced personal burden.
• Setmelanotide was generally well-tolerated, with no new safety signals and common adverse events including skin hyperpigmentation and vomiting.
Rhythm Pharmaceuticals HR Chief Sells Shares Amid Positive Clinical and Financial Outlook
• Rhythm Pharmaceuticals' HR chief, Pamela Cramer, sold $585,940 worth of stock under a pre-established trading plan, while also exercising stock options.
• The company reported a 48% year-over-year increase in global net revenue in Q3 2024, driven by sales of IMCIVREE, and anticipates Phase III data for acquired hypothalamic obesity in early 2025.
• Rhythm is advancing its clinical programs, expecting to complete enrollment in multiple trials by year-end and initiate dosing for new indications in early 2025.
• Despite not being profitable over the last twelve months, Rhythm Pharmaceuticals boasts impressive gross profit margins and strong stock performance, with a 133.08% price increase over the past year.
Rhythm Pharmaceuticals Reports Strong Q3 2024 Driven by IMCIVREE Sales, Advances Hypothalamic Obesity Program
• Rhythm Pharmaceuticals reported a 48% year-over-year increase in global net revenue, reaching $33.3 million in Q3 2024, driven by IMCIVREE sales for Bardet-Biedl Syndrome (BBS).
• The company is advancing its clinical programs, with topline data from a Phase III trial for acquired hypothalamic obesity expected in the first half of 2025.
• A PDUFA date for expanding IMCIVREE's label to include children ages two to six is set for December 26, 2024, potentially expanding the patient opportunity.
• Rhythm anticipates sufficient cash to fund operations into 2026, with reduced operating expense guidance for 2024.
GLP-1 Receptor Agonists Spearhead Obesity Treatment Advancements
• Semaglutide (WEGOVY) marked the resurgence of GLP-1R agonists for obesity treatment, gaining FDA approval in June 2021 and achieving blockbuster status with $7.73 billion in sales by 2023.
• Tirzepatide (ZEPBOUND), a GIPR/GLP-1R co-agonist, and setmelanotide (IMCIVREE), an MC4R agonist, have expanded the therapeutic landscape for obesity, addressing different mechanisms of action.
• Obesity, a chronic disease affecting millions globally, heightens the risk of type 2 diabetes, heart disease, and certain cancers, emphasizing the need for safe and effective anti-obesity medications.
September 2024: FDA Actions Span Diabetes, Neurology, and Rare Diseases
• The FDA approved Embecta's tubeless patch pump for insulin delivery in adults with type 1 and type 2 diabetes, offering a 300-unit reservoir based on patient feedback.
• Sparsentan (Filspari) received full FDA approval to slow kidney function decline in adults with primary IgA nephropathy (IgAN), based on positive Phase 3 PROTECT study data.
• Approvals for arimoclomol (Miplyffa) and levacetylleucine (Aqneursa) mark the first specific treatments for neurological symptoms of Niemann-Pick disease type C (NPC).
• Dupilumab (Dupixent) gained approval for COPD, chronic rhinosinusitis with nasal polyps, and was submitted for label expansion for adult growth hormone deficiency.
FDA Grants Priority Review for Setmelanotide sNDA in Young Children with Rare Genetic Obesity
• The FDA has accepted Rhythm Pharmaceuticals' sNDA for setmelanotide, seeking approval for children aged 2-6 with obesity due to Bardet-Biedl syndrome or POMC/LEPR deficiency.
• The sNDA is supported by Phase 3 trial data showing a 3.04 mean reduction in BMI-Z score and an 18.4% mean reduction in BMI with setmelanotide treatment.
• The FDA has granted Priority Review with a PDUFA goal date of December 26, 2024, potentially offering a precision therapy for young patients with rare MC4R pathway diseases.
• Setmelanotide is currently approved for patients 6 years and older with specific genetic obesity conditions, and this expansion could positively affect younger children and their families.
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