Setmelanotide Acetate

BMI显著下降！突破性疗法获FDA优先审评资格 Rhythm Pharmaceuticals宣布，美国FDA已受理其药品setmelanotide的补充新药申请（sNDA），用于治疗继发性下丘脑性肥胖，并授予优先审评资格。该申请的PDUFA目标日期为2025年12月20日。与此同时，欧洲药品管理局（EMA）也已受理该药品扩展适应症的监管申请。Setmelanotide是一种黑皮质素-4受体（MC4R）激动剂，此前已获FDA与EMA批准，用于治疗由Bardet-Biedl综合征及POMC、PCSK1或LEPR基因缺陷导致的肥胖。该疗法曾获FDA授予突破性疗法认定，用于治疗下丘脑性肥胖。 本次扩展适应症申请主要基于关键临床3期试验TRANSCEND的积极结果。这是一项全球性研究，纳入120例继发性下丘脑性肥胖患者。试验达到主要终点：setmelanotide治疗组患者在52周时平均身体质量指数（BMI）较基线下降16.5%，而安慰剂组则上升3.3%，两组间差异具有高度统计学意义（p<0.0001）。经安慰剂校正后，治疗组患者BMI降低幅度达19.8%，显示出显著且具有临床意义的疗效。 创新眼药水达3期试验主要终点！上市申请即将递交 Nicox宣布，其创新一氧化氮（NO）释放型比马前列素滴眼液NCX 470 0.1%在Denali临床3期试验中达到了主要终点。在这项涵盖696例开角型青光眼或眼压过高患者的研究中，每日一次NCX 470给药在降低基线眼压（IOP）方面，与标准治疗相比，达到非劣效性。结果显示，NCX 470的眼压下降幅度为7.9至10.0 mmHg，而标准治疗为7.1至9.8 mmHg。在预设的次要疗效分析中，NCX 470在六个时间点中的五个时间点在数值上表现出优势，并在其中三个时间点达到统计学显著差异（p<0.05），尽管未能获得整体统计学上的优效性。 该结果与该药物在2022年成功完成的首个3期临床试验Mont Blanc一致，进一步确认了NCX 470在降低眼压方面的疗效，为后续的监管申报奠定了坚实基础。公司表示，这一数据支持其计划于2026年上半年向美国FDA递交的新药申请（NDA）。 3.5亿美元！Kite收购体内细胞疗法公司 日前，Kite宣布达成协议，将以总额高达3.5亿美元收购Interius BioTherapeutics。Interius是一家专注于体内CAR疗法开发的生物技术公司。此次收购将进一步丰富Kite在细胞治疗领域的专业能力，通过引入Interius的体内整合平台，进一步强化Kite在创新疗法领域的布局。 与传统CAR-T疗法需经历细胞采集、改造及回输的繁琐流程不同，Interius的平台可直接在患者体内生成CAR-T细胞，且仅需一次静脉输注即可完成治疗，并无需预处理化疗或复杂的细胞操作。这一“现货型”且个体化的治疗方式有望实现更持久的疗效。平台的模块化架构不仅可快速应用于不同疾病领域，还能在生产规模上具备灵活性，为无法接受现有细胞疗法、尤其是病情进展迅速的患者带来新的治疗机会。 参考资料： [1] Nicox Announces Positive Results from the NCX 470 Phase 3 Denali Trial in Glaucoma Patients. Retrieved August 22, 2025 from  https://www.nicox.com/wp-content/uploads/EN_NCX470DenaliToplineAugust2025_PR_FINAL.pdf [2] Rhythm Pharmaceuticals Announces FDA Acceptance of sNDA for Setmelanotide in Acquired Hypothalamic Obesity. Retrieved August 22, 2025 from https://www.globenewswire.com/news-release/2025/08/20/3136704/0/en/Rhythm-Pharmaceuticals-Announces-FDA-Acceptance-of-sNDA-for-Setmelanotide-in-Acquired-Hypothalamic-Obesity.html [3] Kite to Acquire Interius BioTherapeutics to Advance In Vivo Platform. Retrieved August 22, 2025 from https://www.businesswire.com/news/home/20250820272168/en/Kite-to-Acquire-Interius-BioTherapeutics-to-Advance-In-Vivo-Platform 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

– U.S. Food and Drug Administration accepts sNDA for filing with priority review; sets PDUFA goal date of December 20, 2025 — – European Medicines Agency accepts and validates submission for Type II variation MAA for setmelanotide to treat acquired hypothalamic obesity – – Company to host “Commercial Readiness for Acquired Hypothalamic Obesity,” event for investors and analysts on Wednesday, September 24, in Boston – BOSTON, MA, USA I August 20, 2025 I Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the company’s supplemental New Drug Application (sNDA) for setmelanotide seeking approval for the treatment of conditions associated with acquired hypothalamic obesity. The FDA has granted Priority Review of the sNDA and assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 20, 2025. Additionally, the European Medicines Agency (EMA) has confirmed validation of the Type II variation submission to the Marketing Authorization Application (MAA) for setmelanotide for the same indication. The application review began on August 16, 2025, by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the European Commission (EC) regarding potential approval. Setmelanotide is a melanocortin-4 receptor (MC4R) agonist, previously approved as IMCIVREE ® by the FDA, the EMA, and UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) for obesity due to Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiencies. “Taken together, these important milestones represent a crucial step in our urgent mission to bring forward the first approved treatment for patients with acquired hypothalamic obesity,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “Treatment approaches indicated for general obesity offer limited long-term efficacy for patients living with acquired HO, who face unique challenges including reduced energy expenditure and increased hunger or hyperphagia specifically resulting from MC4R pathway impairment due to hypothalamic injury. We’re committed to working closely with regulators to make setmelanotide available to the patient community as quickly as possible.” The sNDA and Type II Variation are supported by statistically significant and clinically meaningful data from the pivotal Phase 3 TRANSCEND trial of setmelanotide in 120 patients with acquired hypothalamic obesity. Topline results from TRANSCEND, the largest and longest randomized, placebo-controlled trial in acquired hypothalamic obesity to date, were presented in an oral session at the Endocrine Society’s Annual Meeting in April 2025. The global study met its primary endpoint, with a statistically significant -19.8% placebo-adjusted reduction in body mass index (BMI). For the primary endpoint of mean BMI change from baseline, study participants on setmelanotide therapy (n=81) achieved a -16.5% reduction compared with a +3.3% increase among patients on placebo (n=39) at 52 weeks (p<0.0001). Adult patients (age 18 and older; n=49) achieved a -19.2% placebo-adjusted BMI reduction at 52 weeks, and pediatric patients (younger than age 18; n=71) achieved a -20.2% placebo-adjusted BMI reduction at 52 weeks. Setmelanotide was generally well tolerated in the TRANSCEND study. The most common treatment-emergent adverse events (affecting >20% of participants) were nausea, vomiting, diarrhea, injection site reaction, skin hyperpigmentation and headache. Commercial Readiness for Acquired Hypothalamic Obesity Rhythm will host “Commercial Readiness for Acquired Hypothalamic Obesity,” an event for investors and analysts on Wednesday, September 24, 2025, from 8:30 a.m. to 11:30 a.m. ET in Boston, MA to review U.S. launch plans. The event will also feature insights from leading physicians about the urgent need to treat patients with acquired hypothalamic obesity. A live webcast of the event will be available under “Events and Presentations” in the Investor Relations section of the Rhythm Pharmaceuticals website at https://ir.rhythmtx.com/ . The archived webcast will be available on Rhythm Pharmaceuticals’ website approximately two hours after the event and will be available for 30 days following the event. About the Phase 3 TRANSCEND Trial The global, randomized, double-blind, placebo-controlled Phase 3 TRANSCEND trial evaluated the efficacy and safety of setmelanotide in patients with acquired hypothalamic obesity. A total of 120 patients aged 4 years and older were randomized 2:1 to either a daily subcutaneous injection of setmelanotide or placebo. The primary endpoint was mean percent change in body mass index (BMI) from baseline after 52 weeks of treatment. Secondary endpoints assessed daily hunger, hyperphagia (extreme unsatisfied drive to consume food), weight, quality of life, and safety and tolerability. A supplemental cohort of 12 Japanese patients remains ongoing with completion and topline data anticipated in the first quarter of 2026. About Acquired Hypothalamic Obesity Acquired hypothalamic obesity is a rare form of obesity that occurs following physical injury or structural abnormality of the hypothalamus with MC4R pathway disruption and other functional impairment. The MC4R pathway is responsible for controlling physiological functions such as energy expenditure, hunger and weight regulation. Acquired hypothalamic obesity most frequently follows the growth or treatment of craniopharyngioma, astrocytoma or other hypothalamic-pituitary tumors. Additional causes of injury may include traumatic brain injury, stroke or inflammation. Due to impairment of the MC4R pathway, patients experience reduced energy expenditure and increased hunger or hyperphagia, leading to accelerated and sustained weight gain most commonly beginning within six to 12 months following injury. Rhythm estimates there are 5,000 to 10,000 people living with acquired hypothalamic obesity in the U.S. and 3,500 to 10,000 people living with acquired hypothalamic obesity in the EU. About Rhythm Pharmaceuticals Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE ® (setmelanotide), an MC4R agonist is approved by the FDA to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency. Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists bivamelagon and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide Indication In the United States, setmelanotide is indicated to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). In the European Union and the United Kingdom, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. In the European Union and the United Kingdom, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Please see the full Prescribing Information for additional Important Safety Information. About Rhythm Pharmaceuticals Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE ® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the FDA to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency. Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists bivamelagon and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. SOURCE: Rhythm Pharmaceuticals