Setmelanotide Acetate

本文承接降糖减重专题【连载一】GLP-1浪潮下的代谢变局【连载一】 在解析了GLP-1的浪潮后，本期我们将聚焦中枢轴，为您拆解MC4R与Amylin赛道的最新破局之路。 03 中枢轴 CNS & Satiety 1 MC4R 黑皮质素4受体（MC4R）是一种G蛋白偶联受体，参与调节能量稳态、食欲和性功能。MC4R由α-促黑素细胞激素（α-MSH）激活，在代谢过程中发挥关键作用，并与人类某些类型的肥胖症相关。在小鼠模型中，MC4R已被证明可以调节摄食行为、代谢、生殖等功能。 [1] GLP-1 receptor pathway [2] 从机制层面来看，MC4R的信号传导远比简单的“开关”复杂。除了经典的Gs蛋白-cAMP通路外， β -arrestin信号通路和钙离子（Ca 2+ ）调节也深度参与其中，这种多维度的信号网络为药物开发提供了巨大的潜力，同时也带来了挑战。 [2] 然而，MC4R领域的魅力正在于其信号传导的双向可逆性： 激动剂（ agonists）: 通过“激活”受体（如模拟内源性 α -MSH），传递饱腹感信号，从而抑制食欲、增加能量消耗并减轻体重。 反向激动剂/拮抗剂（Inverse Agonists/Antagonists）：通过“阻断”受体或抑制其本底活性（如模拟内源性AgRP），传递饥饿信号，从而刺激食欲、降低代谢并增加体重。 尽管机制明确，但MC4R的药物研发之路曾充满坎坷。十多年前，多家跨国制药巨头的相关项目均因副作用等挑战而折戟沉沙。随着Rhythm Pharmaceuticals的率先突破，这一领域迎来了转机。 2020年，其MC4R激动剂Imcivree（通用名：Setmelanotide）成功上市，成为FDA批准的首个用于慢性体重管理的精准疗法。Imcivree旨在直接解决由黑皮质素-4（MC4）受体通路基因缺陷引起的肥胖根本原因。此外，其第二代口服药物bivamelagon在获得性下丘脑肥胖症中也取得了积极的二期临床数据，极大地重燃了整个领域的研发热情。 如今，Superluminal Medicines、Congruence Therapeutics等初创公司正蓄势待发，计划将其MC4R靶向药物推入临床阶段。正如Superluminal首席执行官Cony D’Cruz所言，Rhythm的成功“出色地验证了这一领域”，不仅为后来者降低了生物学风险，更使他们能够更专注于平台技术的创新与新药的深度开发。 2 Amylin/CALCR 胰淀素（amylin）是由37个氨基酸组成的饱腹感多肽激素，存储在胰腺β细胞中，当营养物质输送到小肠时，胰淀素将与胰岛素一起被β胰腺细胞释放到分泌到血液中，和胰岛素水平同步升高和降低。 胰淀素具有抑制胃排空、控制食欲的功能，并且能够抑制胰高血糖素的分泌，这在维持血糖水平方面具有重要作用。它的分泌会随着血糖水平的变化而进行调节。当血糖水平升高时，胰淀素的分泌增加，这有助于降低血糖水平；而在血糖降低时，胰淀素的分泌则会减少。 胰淀素的这些代谢调节功能均是由胰淀素受体 (Amylin receptors, AMYRs) 介导完成的，因此，这类受体成为了治疗糖尿病和肥胖症的重要药物靶标。 胰淀素受体是一类特殊的蛋白异二聚体，由降钙素受体（CALCR/CTR）和受体活性修饰蛋白（RAMPs）形成的复合物。RAMPs是一系列I型单跨膜蛋白，它们与G蛋白偶联受体形成异源二聚体，分为三种亚型：RAMP1，RAMP2和RAMP3。这三个RAMP具有相似的基本结构，但氨基酸序列中只有约30%的同一性。CALCR和RAMP1形成的复合物AMY1，CALCR和RAMP2形成的复合物AMY2，CALCR和RAMP3形成的复合物AMY3。[3] 与GLP-1类药物相比，Amylin在减重过程中能显著提升肌肉保留率，减少肌肉流失，实现“减脂少减肌”的效果，同时胃肠道耐受性更好。这一机制使 AMY/CALCR 靶点成为糖尿病及肥胖症治疗的重要药物靶标，也为新一代减重与代谢调节疗法提供了科学依据。 胰淀素的疾病关联 在2型糖尿病中，胰淀素不仅是胰岛素的“搭档”，更是病理进程的关键参与者。其核心关联在于胰岛淀粉样蛋白沉积——这是2型糖尿病的典型病理特征。由胰淀素异常折叠形成的淀粉样纤维会在胰岛内积聚，这种沉积物具有细胞毒性，会直接损伤β细胞膜、诱导β细胞凋亡。这不仅导致功能性β细胞数量减少，还会破坏胰岛微环境，进一步加剧胰岛素分泌不足与血糖失控。 除了在胰腺内的作用，胰淀素受体的核心组分CALCR（降钙素受体）在其他疾病中也扮演着重要角色。在骨骼系统中，CALCR是调控骨代谢的关键受体，主要介导降钙素对破骨细胞的抑制作用，从而抑制骨吸收、维持骨密度，其基因多态性与骨质疏松症的易感性密切相关。此外，CALCR与RAMPs蛋白形成的异二聚体（如AMY1受体）在神经系统中分布广泛，与偏头痛及神经性疼痛的信号传导密切相关，拓展了其在代谢以外的治疗领域价值。[3,4] 针对代谢疾病治疗领域的多元化靶点需求，吉满生物构建了高度定制化的产品矩阵：针对MC4R、AMY等相关肥胖和糖尿病靶点的药物，我们推出一系列细胞系产品，为代谢类疾病新药研发过程助力。（详情咨询吉满客服：18916119826） Amylin/CALCR竞争格局 放眼整个行业，越来越多的药企将 Amylin 视为 GLP-1 之外的下一个增长极。诺和诺德、礼来、罗氏等巨头纷纷抢滩布局,在研管线覆盖Amylin类似物、AMYR激动剂、AMYR/GLP-1R双重激动剂、AMYR/CALCR双重激动剂等多元路径。 Amylin/CALCR主要管线及竞争格局 [4-7] 普兰林肽仍是唯一上市药物，诺和诺德领跑临床管线，其在Amylin领域进行了多维度布局，涵盖药物研发、临床试验及联合疗法探索。 去年底，其公告宣布已向 FDA 递交每周一次注射用 CagriSema (GLP-1 + Amylin联合疗法)的新药申请，配合低热量饮食和增加体育锻炼，用于减轻肥胖或超重成人患者的体重，并长期维持体重减轻的效果，尤其适用于伴有至少一种体重相关合并症的患者。如果获得批准，CagriSema 将成为首个注射用 GLP-1 受体激动剂和胰淀素类似物复方制剂。 此外，诺和诺德今年陆续启动Amycretin的多项三期临床试验，覆盖减重、2型糖尿病、阻塞性睡眠呼吸暂停（OSA）及骨关节炎等多项适应症的三期临床试验。[5-6] 礼来推出迭代的偏向性Amylin类似物 ELoralintide  ，也启动针对顽固性肥胖\肥胖、肥胖合并二型糖尿病、OSA的三期临床。 而国内药企也在加速布局 Amylin 赛道，其中博瑞医药BG1812进展最为领先。临床前数据显示，BG1812在饮食诱导的肥胖大鼠模型中展现出强效减重效果，且与BG0504（GLP-1/GIP激动剂）联用时，减重协同作用显著。11月4日，博瑞医药在Clinicaltrials.gov网站上注册了Amylin类似物BGM1812的美国一期临床试验，加速迈入全球竞争节奏。[8] 03 总结 MC4R与Amylin作为代谢领域极具潜力的两大靶点，正引领着新一代降糖减重疗法的革新。MC4R激动剂通过模拟α-MSH激活中枢饱腹信号，直接从源头调节能量稳态，其双向调节机制（激动剂抑食、拮抗剂增食）为精准治疗不同类型的肥胖症提供了理论基础。 与此同时，Amylin靶点凭借其独特的“减脂少减肌”优势及对胃排空的调节作用，正成为GLP-1之外的强力补充，诺和诺德通过CagriSema联合疗法及新一代多靶点激动剂Amycretin的密集布局，正将适应症从单纯减重拓展至2型糖尿病、阻塞性睡眠呼吸暂停及骨关节炎等复杂代谢共病领域。 这一波创新浪潮不仅验证了GLP-1与Amylin多靶点协同以及MC4R精准调控在提升减重效率与改善代谢指标上的优越性，更标志着代谢治疗正迈向更精细化、个性化的全新时代。 吉满生物代谢类疾病的靶向药研发平台 肥胖和2型糖尿病（T2D）仍然是一个紧迫的全球健康危机。与此同时，多个与能量代谢、胰岛素分泌、食欲调控等作用机制紧密相关的靶点，在药物研发中同样扮演着关键角色，共同构成了这一领域的完整机制拼图。 合规基石与研发加速双驱动 我们已成功获得HEK293、Jurkat E6.1、CHO-K1 等细胞商业使用授权，提供全面的溯源文件，赋能合作伙伴从临床前开发到IND/BLA 阶段进行合规研究，帮助客户规避法律风险并加速商业化进程。 1 靶点相关细胞系：适用于药物功能筛选、活性评价、药效学研究及信号通路验证 2 高活性重组蛋白：满足结合分析、筛选及免疫研究需求 3 高特异性抗体： 提供经严格验证的抗体产品，支持流式细胞术、免疫组化、Western Blot、ELISA 等多种检测应用，确保实验结果准确可靠 全靶点覆盖的精准工具体系 针对代谢疾病治疗领域的多元化靶点需求，吉满生物构建了高度定制化的产品矩阵：针对GLP-1、GIP、GCG、MC4R、AMY、ActRII及其他相关肥胖和糖尿病靶点的药物，我们推出一系列细胞系、抗体和蛋白产品，为代谢类疾病新药研发过程助力。（详情咨询吉满客服：18916119826） MC4R产品及数据展示 数据展示 GM-C41294 H_MC4R Reporter HEK-293 Cell Line分别使用a-MSH、Setmelanotide验证结果 使用a-MSH药物的cAmp验证结果 本产品经α -MSH 与 Setmelanotide严格的功能实测，结果显示细胞对药物响应准确、信号传导通畅，高效助力药物筛选与活性评价。 AMY产品及数据展示 部分数据展示 GM-C26533 H_CALCR RAMP3(AMY3) Reporter CHO-K1 Cell Line使用Amylin稳定性验证结果 细胞传代至少27代后，信号响应仍然稳定 使用Calcitonin药物验证结果 使用Amylin药物cAmp验证结果 使用Calcitonin药物cAmp验证结果 本产品经 Calcitonin 与 Amylin类似物严格的功能实测，细胞对药物响应准确，功能活性稳定、结果可靠。 联系我们 吉满生物(Genomeditech)成立于2011年，是专业从事生物科技服务和前沿技术研发的高新技术企业。吉满生物专注为生物药开发赋能，自主创立了国内知名的细胞系品牌-DDXCELL，目前已布局近400个热门靶向药靶点，超1500株现货单克隆细胞系，涵盖GPCR、细胞因子、免疫检查点、TAA等多领域，做到进口细胞的国产替代。此外，吉满生物还可在药物研发进程中提供一系列抗体、蛋白产品，旨在为客户提供高效的研发工具和解决方案! 扫码咨询 扫码找现货  参考资料 [1]https://en.wikipedia.org/wiki/Melanocortin_4_receptor [2]Fatima MT, Ahmed I, Fakhro KA, et al. Melanocortin-4 receptor complexity in energy homeostasis,obesity and drug development strategies. Diabetes Obes Metab. 2022 Apr;24(4):583-598. [3] Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.Dahl, Kirsten et al.The Lancet, Volume 406, Issue 10499, 149-162. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2825%2901185-7/abstract [4] https://en.wikipedia.org/wiki/Amylin [5]https://www.novonordisk.com/science-and-technology/r-d-pipeline.html [6]https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916470 [7]https://metsera.com/pipeline/ [8]Home | ClinicalTrials.gov

BOSTON, May 06, 2026 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced that David Meeker, M.D., Chairman, President and Chief Executive Officer, will participate in a fireside chat at the upcoming Bank of America Global Healthcare Conference on Wednesday, May 13 at 3:00 p.m. PT in Las Vegas. The fireside chat will be webcasted and available under “Events & Presentations” in the Investor Relations section of the Company’s website at . A replay of the webcast will be available on the Rhythm website for 30 days following the presentation. 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 U.S. Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 4 years and older with acquired hypothalamic obesity, 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. The European Commission (EC) has authorized setmelanotide for the treatment of obesity and control of hunger in patients 4 years of age and above with acquired hypothalamic obesity. 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 adults and pediatric patients aged 4 years and older with acquired hypothalamic obesity, 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 confirmed by genetic testing 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. Limitations of Use Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign Other types of obesity not related to acquired HO, BBS, or POMC, PCSK1 or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity. Important Safety Information CONTRAINDICATIONS Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. WARNINGS AND PRECAUTIONS Disturbance in Sexual Arousal: Spontaneous penile erections and increased frequency of penile erections in males have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention. Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE. Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation occurred in the majority of IMCIVREE-treated patients. IMCIVREE may also cause development of new melanocytic nevi or darkening of pre-existing nevi. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions. Acute Adrenal Insufficiency with Acquired HO: Patients with acquired HO and secondary adrenal insufficiency reported serious adverse reactions related to acute adrenal insufficiency in 5% of IMCIVREE-treated patients and no placebo-treated patients. In patients with secondary adrenal insufficiency, monitor for clinical signs of acute adrenal insufficiency. Sodium Imbalance in Patients with Acquired HO and Central Diabetes Insipidus: Patients with acquired HO and concomitant central diabetes insipidus (DI)/arginine vasopressin (AVP) deficiency reported hyponatremia in 6% of IMCIVREE-treated patients and 2% of placebo-treated patients and hypernatremia in 5% of IMCIVREE-treated patients and 4% of placebo-treated patients. Monitor serum sodium levels with changes in fluid intake and hydration status. Adjust the doses of concomitant therapies for DI/AVP deficiency as needed. ADVERSE REACTIONS Most common adverse reactions (incidence ≥20% in at least 1 indication) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONS Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at 1-800-FDA-1088 or . See section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe. Please see the full Prescribing Information for additional Important Safety Information. Forward-looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the safety, efficacy, potential benefits of, and clinical design or progress of any of our products or product candidates at any dosage or in any indication; our participation in upcoming events and presentations, including at the upcoming Bank of America Global Healthcare Conference, including the content, date and timing of any of the foregoing. Statements using words such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks, uncertainties and other important factors, including those discussed under the caption “Risk Factors” in Rhythm’s Quarterly Report on Form 10-Q for the three months ended March 31, 2026, and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contacts: David Connolly Head of Investor Relations and Corporate Communications Rhythm Pharmaceuticals, Inc. 857-264-4280 dconnolly@rhythmtx.com Kate Walsh Director, Corporate Communications Rhythm Pharmaceuticals, Inc. (857) 264-4280 kwalsh@rhythmtx.com