A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Pharmacologic Agents in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes

The main purpose of the SYNERGY-OUTCOMES study is to find out whether retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in people with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study will enroll adults who have MASLD based on non-invasive tests (NITs), which indicate they are more likely to develop MALO. Participants will be randomly assigned within a Master Protocol to receive either retatrutide (N1T-MC-RT01), tirzepatide (N1T-MC-TZ01) or placebo. The trial plans to enroll about 4,500 adults and will run for approximately 224 weeks. Participants may have up to approximately 25 to 30 clinic visits throughout the study to monitor their health, complete study procedures, and assess liver function and disease progression.
Once the study is complete, eligible participants may participate in an optional 2-year extension study, in which all participants will receive either retatrutide or tirzepatide, even if they received placebo in the main study.

开始日期2025-10-15

申办/合作机构

Eli Lilly & Co.

NCT06982846

/ Recruiting临床1期

A Randomized, Placebo-Controlled, Parallel Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia

The purpose of this study is to measure the effect of retatrutide versus placebo, administered every week, on time to recovery from hypoglycemia during hypoglycemic clamp in participants with Type 2 Diabetes Mellitus (T2DM) following 16 weeks of treatment.

开始日期2025-06-06

申办/合作机构

Eli Lilly & Co.

NCT06982859

/ Recruiting临床1期

A Phase 1, Investigator- and Participant-Blinded Study to Evaluate the Effect of Retatrutide on α- and β- Cell Function and Insulin Sensitivity in Adult Participants With Type 2 Diabetes Mellitus

The primary objective of Study GZQG is to compare the effect of retatrutide and placebo on total clamp disposition index (cDI) after 28 weeks of treatment.

开始日期2025-06-02

申办/合作机构

Eli Lilly & Co.

100 项与瑞他鲁肽相关的临床结果

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100 项与瑞他鲁肽相关的转化医学

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100 项与瑞他鲁肽相关的专利（医药）

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项与瑞他鲁肽相关的文献（医药）

2025-12-31·Journal of Pharmaceutical Policy and Practice

Compounded glucagon-like peptide-1 receptor agonists for weight loss: the direct-to-consumer market in Colorado

Article

作者: Saseen, Joseph J. ; Dardouri, Mouna ; Moore, Gina D. ; DiStefano, Michael J. ; Nair, Kavita V.

Background:

High prices and other access barriers have contributed to the rise of a market for compounded glucagon-like peptide-1 receptor agonists for weight loss in the United States. This market has not been systematically studied. We conducted a pilot study to assess the prevalence, characteristics, and advertising content of direct-to-consumer providers of compounded glucagon-like peptide-1 products for weight loss in Colorado.

Methods:

We conducted a cross-sectional study of websites advertising compounded glucagon-like peptide-1 products for weight loss in Colorado. Websites were identified using Google searches focused on census-defined statistical areas. Searches were conducted between March 21 and April 12, 2024. Data collected from websites included physical addresses, business type, highest reported staff credential, advertised glucagon-like peptide-1 products, whether businesses referred to Food and Drug Administration approval when describing products, and whether businesses referred to products as 'generic'.

Results:

We identified 93 business websites advertising compounded glucagon-like peptide-1 products for weight loss corresponding to 188 physical locations throughout Colorado. Most businesses were self-categorized as medical/health spas (33/93) or weight loss services (26/93). Advertised products included semaglutide (92/93), tirzepatide (40/93), liraglutide (2/93), and retatrutide (1/93). Advertised combination products included B vitamins (8/93), levocarnitine (1/93), mannitol (1/93), BPC-157 (1/93), and glycine (1/93). Seven websites advertised oral formulations. Additionally, 41/93 websites referred to Food and Drug Administration approval in their descriptions of compounded products and 5/93 referred to products as 'generic'.

Conclusion:

This study identified several instances of unapproved glucagon-like peptide-1 products being compounded and advertised in Colorado. Additionally, 1 product was advertised as compounded with BPC-157, a substance determined by the Food and Drug Administration to be unsafe for compounding. This study also identified numerous examples of misleading claims regarding the regulatory status of compounded glucagon-like peptide-1 products. Regulatory action is needed to ensure the benefits of compounded GLP-1 products outweigh the risks.

2025-12-01·Current Cardiovascular Risk Reports

Triple Agonism Based Therapies for Obesity

Review

作者: Papamargaritis, Dimitris ; Surti, Farhaana ; Goldney, Jonathan ; Hamza, Malak ; Davies, Melanie J

Abstract:

Purpose of the Review:

Glucagon-like peptide 1 (GLP-1) receptor agonists (RA) have transformed obesity and type 2 diabetes (T2D) management. Tirzepatide, the first dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RA approved for both conditions, has paved the way for next-generation incretin-based therapies. Among these, triple agonists targeting GLP-1, GIP, and glucagon receptors represent a promising next step. This review outlines the rationale for their development and summarizes clinical trial data, focusing on retatrutide, the most advanced candidate.

Recent Findings:

Retatrutide is the first triple agonist (acting on GLP-1/GIP/glucagon receptors) with published phase 2 data in people with obesity as well as in people with T2D. Retatrutide achieved up to 24.2% mean weight loss after 48 weeks in individuals with obesity and 16.9% in those with T2D after 36 weeks. In the T2D study, HbA1c improved by 2.2%, with 82% of participants reaching HbA1c ≤ 6.5%. Retatrutide also improved multiple cardiometabolic parameters, including blood pressure, lipids, waist circumference, and liver fat (82% reduction in hepatic steatosis). Gastrointestinal symptoms were the most common side effects; no major safety concerns were observed. A comprehensive phase 3 program is ongoing to evaluate efficacy, safety, and cardiovascular/renal outcomes in people with obesity and/or T2D. Other unimolecular triple agonists and combination regimens involving tirzepatide with additional mono agonists are also in development.

Summary:

Retatrutide, a triple agonist now in phase 3 trials, has the potential to become the most effective pharmacological treatment for obesity while also offering substantial benefits in T2D management and other cardiometabolic risk factors.

2025-12-01·DIABETES OBESITY & METABOLISM

Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study

Article

作者: Kanu, Chisom ; Boye, Kristina S. ; Martin, Corby K. ; Coskun, Tamer ; Williamson, Suzanne ; Hartman, Mark L. ; Poon, Jiat Ling ; Goetz, Iris ; Lou, Jitong

Abstract:

Aims:

To determine whether adults with type 2 diabetes (T2D) treated with retatrutide report greater changes in self‐reported appetite, dietary restraint, and disinhibition compared to placebo or dulaglutide and to examine associations with weight change.

Materials and Methods:

These pre‐specified exploratory analyses examined changes from baseline in Appetite Visual Analogue Scale (VAS) and Eating Inventory (EI) scores after 24 and 36 weeks of once‐weekly treatment with placebo, dulaglutide 1.5 mg, or retatrutide 0.5, 4, 8, or 12 mg in 275 adults with T2D. Changes from baseline with retatrutide were compared to those with placebo and dulaglutide. Post‐hoc correlations between changes in body weight and Appetite VAS/EI scores were also examined.

Results:

Compared with placebo, participants who received retatrutide ≥4 mg reported greater reductions from baseline in overall appetite, hunger, and prospective food consumption (l at Week 24 (all p <0.05)). Differences versus dulaglutide were less consistent. Improvements from baseline versus placebo in EI Perceived Hunger and Disinhibition were greater in participants who received retatrutide 8 and 12 mg at Weeks 24 and 36. Dietary Restraint increased from baseline versus placebo only in participants who received retatrutide 12 mg at Week 36 (all p <0.05). Reductions in Perceived Hunger and Disinhibition, and increases in Dietary Restraint were significantly correlated with reductions in body weight at Week 36 ( r = 0.28, r = 0.36, and r = 0.31, respectively).

Conclusions:

Perceived hunger and tendency to overeat (disinhibition) were reduced with higher doses of retatrutide, compared with placebo. Greater weight reduction was associated with decreased perceived hunger and disinhibition and increased dietary restraint.

Plain Language Summary:

What Is the Context and Purpose of this Research Study?:

Retatrutide is a new treatment currently being developed for people with obesity and people with type 2 diabetes. This study compared the changes in appetite and eating behaviours of adults with T2D who were treated with retatrutide, dulaglutide (an alternative treatment), or placebo (i.e., no treatment).We examined changes in feelings of hunger, satisfaction and fullness, the desire to eat certain types of foods (e.g., sweet, salty or fatty foods), the tendency to overeat (e.g., when stressed), and conscious efforts to limit food intake. We also examined the potential link between changes in appetite or eating behaviours and changes in weight during retatrutide treatment.

What Was Done?:

Adults with type 2 diabetes who participated in this trial completed two questionnaires that measured their eating habits at several time points during the 36‐week period in which they received treatment. The questionnaire responses of people who received retatrutide each week (1–4 different doses) were compared with the responses of people who received no treatment (i.e., placebo) and of people who received dulaglutide treatment. Any potential links between the amount of weight reduction people experienced while receiving treatment during the study and their questionnaire responses were also examined.

What Were the Main Results?:

This study showed that adults with type 2 diabetes who received higher doses of retatrutide reported being less likely to feel hungry or overeat compared to those who received no treatment (i.e., placebo) or those who received dulaglutide. On average, people who experienced greater weight reduction also reported being less hungry and less likely to overeat.

What Is the Originality and Relevance of this Study?:

This is the first study to assess changes in appetite and eating behaviours of adults with type 2 diabetes who received retatrutide. Our results suggest that enhanced modification of eating behaviours with retatrutide may assist with weight reduction in adults with type 2 diabetes.

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项与瑞他鲁肽相关的新闻（医药）

2025-11-10

·E药经理人

礼来霸榜、辉瑞再降，默沙东、BMS承压！全球制药营收TOP10再洗牌

撰文| 张烨静随着Q3财报季走入尾声，全球制药巨头再次迎来“大洗牌”。礼来凭借超过50%的营收增速强势登顶，成为本季度最亮眼的存在；同在GLP-1赛道的诺和诺德，曾于今年H1财报季进入跨国药企营收TOP10榜单，与礼来此刻的霸榜相呼应。相比之下，“昔日霸主”辉瑞却成为TOP10中唯一接连“双降”的企业。强生、默沙东、BMS同样增长乏力，整体呈现疲软态势。尽管几家欢喜几家愁，但一个共同的焦虑摆在多数MNC面前：明星药物专利悬崖、核心产品增长见顶后，该如何寻找“下一个重磅炸弹”？生物制药的竞赛强度正不断升级，一个财报季就是一次洗牌。但不变的是，在这个竞技场上，没有永恒的王者，只有持续的创新者。数据来源：公司财报几家欢喜几家愁整体来看，MNC三季度业绩呈现出几家欢喜几家愁的局面。礼来以超高增速“一骑绝尘”，AZ上半年和Q3均实现双位数增长，艾伯维、诺华和赛诺菲也保持在高个位数的增长，展现出一定的业务韧性。与此同时，辉瑞、BMS是榜单中唯二出现营收下滑的MNC，尤其是辉瑞未能守住2024年的榜首位置，延续业绩下滑趋势。此外，默沙东和强生虽然排名基本保持在原先的水平，但持续面临着增长乏力；罗氏Q3增速有所放缓。先看礼来。回顾近两年TOP10榜单，礼来在2024年仅排第9名，到2025年H1升至第6名，如今的Q3已跃居营收榜首，可谓是一路“超车”。今年前三季度，礼来总营收458.87亿美元，同比增长46%，其中Q3营收176.01亿美元，增速达到54%。尤为亮眼的是，Q3净利润为55.83亿，同比增长475.34%，成长势头极为强劲。 “明星产品”替尔泊肽是礼来的绝对增长引擎。前三季度，替尔泊肽创收248.37亿美元，占总营收的半壁江山，增速更是达到了125%。事实上，早在今年上半年，替尔泊肽就以121.3%的增速实现收入147.34亿美元，与司美格鲁肽的差距缩小到约20亿美元。截至前三季度，双方差距已不到10亿美元。此外，礼来和诺和诺德在GLP-1类药物美国处方量上的占比也进一步拉开：上半年分别为57.0%和42.5%，第三季度变为57.9%和41.7%。值得一提的是，今年最后一个季度，礼来在GLP-1领域仍有进展值得期待。其口服小分子GLP-1药物orforglipron计划于年内递交肥胖适应症相关申请，有望在2026年上市后迅速抢占市场份额，而CGR/GIPR/GLP-1R三靶点药物Retatrutide也将完成首个III期研究。总体来看，礼来将2025全年收入预期从600亿-620亿美元再次上调至630亿-635亿美元。业界预计，替尔泊肽全年营收有望在年底反超司美格鲁肽。阿斯利康在前三季度都实现了双位数增长，总收入432.36亿美元，同比增长11%；Q3总营收151.91 亿美元，同比增长10%。前三季度，阿斯利康五大核心业务版块均实现增长，肿瘤、心血管-肾脏-代谢疾病、呼吸与免疫、疫苗与免疫疗法以及罕见病，分别贡献了185.91亿美元（+16%）、98.09亿美元（+5%）、64.93亿美元（+13%）、8.26亿美元（+2%）、67.52亿美元（+6%）的收入。其中，肿瘤药是AZ的第一大业务板块，占了产品总收入的43%。尤其ADC药物表现突出，其HER2 ADC药物Enhertu (DS-8201)，前三个季度销售额达到35.75亿美元，同比增长31%。另一款靶向TROP2的ADC药物Datroway，于2025年1月获得美国FDA批准上市，8月份也首次在中国获批，前九个月销售达到3800万美元。此外，艾伯维、诺华和赛诺菲都保持在高个位数的增长，整体增速稳健。艾伯维目前位列营收TOP10第四，其前三季度总营收445.42亿美元，同比增长8%，其中Q3收入157.76亿美元，同比增长9.1%。按板块来看，其艾伯维自免、神经科学、肿瘤三大领域均正向增长，前三季度分别收入217.80亿美元（+12.3%）、78.06亿美元（+20.3%）和49.91亿美元（+2.6%）。两款重磅自免药物是艾伯维的增长动力，IL-23单抗Skyrizi（利生奇珠单抗）和JAK1抑制剂Rinvoq（乌帕替尼）前三季度分别创收125.56亿美元（+58.1%）和59.30亿美元（+43.3%）。而曾经的“药王”Humira（阿达木单抗）自2023年失去关键专利保护后，业绩持续下滑。2024年，其销售额为89.93 亿美元，同比下降37.6%。今年前三季度，其销售额为32.94亿美元，同比下降55.0%。诺华排在第七名，公司前九个月净销售额达411.96亿美元，同比增长11%，其中Q3净销售额为139.09亿美元，同比增长7%，净利润39.3亿美元，同比增长25%。值得一提的是，公司前三季度已有10个重磅产品的销售额累计超过10亿美元。诺华的业绩“顶梁柱”是降压药Entresto，该药前三季度创收64.9亿美元，同比增长15%。然而，随着关键专利在2025年7月到期，销售额也逐渐承压，Q3营收为18.7亿美元，同比下降1%。推荐阅读 * AZ超罗氏，礼来追赛诺菲，诺华掉出前五，全球制药营收TOP10洗牌 * 礼来狂飙，诺华爆发，百济首进，全球畅销药TOP50变天！专利悬崖潮来袭尽管礼来、AZ均增长亮眼，但从整体来看，MNC的日子普遍不太好过，辉瑞、BMS、默沙东、强生和罗氏均有不同程度的承压。辉瑞格外受到关注。近期，辉瑞出现了多方面的变动——Q3业绩下滑、砍掉11条管线、百亿美元竞价收购。一边是豪赌、一边是撤退，昔日霸主的短期阵痛和长久焦虑，集中地呈现出来。从业绩上看，辉瑞的困境已经不是“新鲜事”。2025年第一季度，辉瑞总营收已经同比下跌8%。前三季度，辉瑞总营收450.22亿美元，同比下降2%，Q3的营收更是由去年同期的177亿美元降至166.5亿美元，同比下降6%；Q3净利润为35.41亿美元，同比下降21%。凭借新冠疫苗Comirnaty和新冠口服药Paxlovid，辉瑞曾成为全球首个年收入超千亿美元的制药企业。但随着市场消退，这两款产品持续下滑。今年第三季度，Paxlovid收入同比暴跌55%，Comirnaty也下降了20%，辉瑞正面临最陡峭的收入断崖。更深的焦虑在于，辉瑞的多款王牌产品即将迎来专利到期。未来五年内，Eliquis、Prevnar13、lbrance、Xtandi将相继面临仿制药冲击。其中，Eliquis今年Q3贡献了20.03亿美元收入，占辉瑞总收入的13.7%，该药将于2026年率先专利到期。因此，无论是砍掉11条管线，还是百亿竞价收购Metsera，都是辉瑞为应对危机采取的腾挪之举。尤其是对Metsera的收购，被视为辉瑞在GLP-1赛道的“放手一搏”。Metsera处于2b期的GLP-1受体激动剂MET-097i支持每月一次注射，在12周的Ⅱ期试验中，受试者体重减少了11.3%，且副作用有限，极具竞争优势。事实上，辉瑞曾早早布局炙手可热的GLP-1赛道，并且多次表示“肥胖产品是公司应对80亿美元的专利危机的潜力增长点”。但随着管线推进不断受挫，辉瑞三款GLP-1激动剂的研发全部终止，业内一度认为辉瑞全面退出该赛道。直到今年9月22日，辉瑞与Metsera达成初步协议，以每股70美元、总价约73亿美元的价格收购该公司，重新落子GLP-1。然而，同样焦虑与迫切的不只辉瑞。曾在今年9月裁员9000人的诺和诺德，也正在积极寻求解法——10月30日，诺和诺德突然提出每股77.75美元，总价约90亿美元的收购要约，要从辉瑞手里抢下Metsera。诺和诺德同样处于专利悬崖的梦魇之下，司美格鲁肽的核心专利将于2026年3月到期，已有多家仿制药虎视眈眈，替尔泊肽的亮眼表现更是带来一重压力。在“前有标兵、后有追兵”的窘境下，诺和诺德正试图通过收购，巩固自身在代谢领域的优势。诺和诺德入局后，一场颇有火药味的竞价就此开启。两家制药巨头展开多轮竞价，辉瑞将报价提升至每股70美元（总价81亿美元），而诺和诺德则报出每股86.2美元（总价100亿美元）。直到在最后阶段，辉瑞将报价提升至与诺和诺德持平的水平，均为每股86.20美元，总价最高达100亿美元，从而达成交易。事实上，不只辉瑞与诺和诺德：未来五年，全球制药业将迎来最恐怖的专利到期潮，默沙东的Keytruda、强生的Darzalex、罗氏的Ocrevus和Vabysmo、BMS的Eliquis和Opdivo等“重磅药”将陆续走入“悬崖”。其中，默沙东K药（Keytruda）的专利将于2028年到期，Evaluate预测其2030年的销售额将比2024年（295亿美元）下滑近一半。今年前三季度，默沙东制药业务收入432.99亿美元，与去年同期基本持平，而K药的销售额达233.03亿美元，同比增长8%，增势已明显趋缓。 O药（Opdivo）则是BMS最突出的资产。为了延长专利保护期，BMS通过推出新剂型和新适应症开发，成功将O药的专利保护期延长至2028年。此外，BMS的Revlimid将在2026年专利到期。今年前三季度，BMS收入356.92亿美元，同比下降1%，Q3营收122.22亿美元，同比增长3%。其中，Opdivo在2025年前三季度保持稳定增长，收入73.56亿美元，同比增长8%。而Revlimid前三季度收入下滑至23.49亿美元，同比下降47%。行业已再次站在关键的转折点——未来五年，前所未有的专利到期潮将席卷大多数MNC。无论是向内“战略收缩”，还是向外“开拓增量”，站在最真实的焦虑面前，穿越周期、寻找下一个增长极，已成为所有MNC的共识。谁才能在下一次“排位赛”里，继续留在高段位？11月24-26日，2025’第十七届中国医药企业家科学家投资家大会（启思会）将在北京海淀盛大召开。启思会将以“结构性拐点”为价值锚点，与行业精英一起，共探中国医药产业高质量发展的路径。扫码报名获得【2025启思会】参会名额扫码进群了解【2025启思会】更多详情大会咨询参会咨询联系人：Mily 联系电话：15801338547 商务合作联系人：Chen 联系电话：18611165131 媒体咨询联系人：Yuvia 联系电话：18811130861 参展咨询为落实国务院和党中央关于生物医药全产业链创新发展的精神，推动我国生物医药产业迈向全球价值链中高端、实现高水平科技自立自强的重要举措。2025第十七届中国医药企业家科学家投资家大会特别组织“十四五”中国医药产业优质供应商系列活动，邀请相关企业【免费参与】联系人：Wenbo 联系电话：13716707405 一审| 黄佳二审| 李芳晨三审| 李静芝精彩推荐大事件 | IPO | 融资&交易 | 财报季 | 新产品 | 研发日 | 里程碑 | 行业观察 | 政策解读 | 深度案例 | 大咖履新 | 集采&国谈 | 出海 | 高端访谈 | 技术&赛道 | E企谈 | 新药生命周期 | 市值 | 新药上市 | 商业价值 | 医疗器械 | IND | 周年庆大药企 | 竞争力20强 | 恒瑞 | 石药 | 中生制药 | 齐鲁 | 复星 | 科伦 | 翰森 | 华润 | 国药 | 云南白药 | 天士力 | 华东 | 上药创新药企 | 创新100强 | 百济 | 信达 | 君实 | 复宏汉霖 | 康方 | 和黄 | 荣昌 | 亚盛｜康宁杰瑞｜贝达｜微芯｜再鼎｜亚虹跨国药企｜ＭＮＣ卓越｜辉瑞｜AZ｜诺华｜罗氏｜BMS｜默克｜赛诺菲｜GSK｜武田｜礼来｜诺和诺德｜拜耳供应链｜赛默飞｜药明｜凯莱英｜泰格｜思拓凡｜康龙化成｜博腾｜晶泰｜龙沙｜三星启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 中国医药手册

财报

2025-11-10

·FierceBiotech

Eli Lilly pens $1.2B pact with Sanegene to better target metabolic RNA meds

Eli Lilly, which markets the obesity blockbuster Zepbound, has a bulging metabolic portfolio.\n Eli Lilly has penned a research pact worth $1.2 billion in biobucks with SanegeneBio to help pinpoint cardiometabolic RNAi medicines at the correct tissues.The agreement centers around Sanegene’s Ligand and Enhancer Assisted Delivery (LEAD) platform, which the Boston-based biotech touts as a potential way to “generate breakthrough therapies for metabolic diseases that could be administered subcutaneously as infrequently as twice per year.”Sanegene is already working on a clutch of its own metabolic-focused RNA meds, headed up by a clinical-stage angiotensinogen-targeting siRNA for which China’s Innovent has scooped up the Asia rights.Saturday’s deal with Lilly involves Sanegene identifying optimized LEAD-based RNAi molecules for an undisclosed number of metabolic targets, with Lilly taking over each program for IND-enabling studies and beyond.In return, the Big Pharma is initially handing over an upfront payment and making an equity investment in Sanegene. While both amounts were also undisclosed in the biotech’s Nov. 8 release, Sanegene did divulge that the combined total of discovery, development, regulatory and commercial milestone payments it could potentially receive from the deal could reach $1.2 billion.\"Partnering with Lilly represents a strong validation of our innovative and differentiated LEAD platform for tissue-selective delivery of RNAi medicines,” Sanegene CEO Weimin Wang, Ph.D., said in the release.“We look forward to working closely with Lilly, a global leader in innovation for metabolic diseases, to unlock novel approaches for the treatment of metabolic disorders and to advance durable, disease-modifying therapies for patients worldwide,” Wang added. Lilly, which markets obesity blockbuster Zepbound, has a bulging metabolic portfolio including next-gen weight loss drugs like orforglipron and retatrutide.Meanwhile, the pharma has stepped up its RNA therapeutics strategy in recent months, including a $13 million upfront deal with Creyon Bio to develop artificial-intelligence-designed oligonucleotide therapies spanning a “a broad range of diseases.” The pharma also tapped Rznomics for a $1.3 billion biobucks deal centered around using the South Korean biotech’s trans-splicing ribozyme platform to develop a hearing loss therapy.In August 2024, Lilly opened a $700 million R&D center in the Boston Seaport, boosting its RNA and DNA research capabilities. Further back, Lilly has clinched RNA-focused deals with the likes of MiNA Therapeutics and ProQR Therapeutics.

寡核苷酸

2025-11-10

·今日头条

风中凌乱的GLP-1及GLP-1/GIP，入场晚的都会废了。。。

后浪森林研究室 | 洛上洲编辑 | 许佳维诺和诺德的司美格鲁肽及礼来的替尔泊肽示范效应引起全球业界跟从，这一行为在中国生物医药界特别突出。随着司美格鲁肽2026年3月专利期尽，司美格鲁肽生物类似物排队列候上市的名单越来越长，最新排队的已达8家，只等发令枪响，蜂拥而上的局面已可预料。而更多的还在后面，仅仅中国A股及H股涉足GLP-1类似药物的企业就高达45家。礼来卷起的纷争根据礼来最新披露，替尔泊肽前三季度收入248.37亿美元，仅略低于诺和诺德司美格鲁肽的254.62亿美元。要知道，这是一个替尔泊肽与司美格鲁肽Ozempic、Rybelsus、Wegovy三个品牌之战的对垒。大概率讲，2025年全年超越应无悬念。况且礼来自研的GLP-1R/GIPR/GCGR三靶点激动剂Retatrutide（研发代号LY3437943）已在临近终点的路上，它有9项正在全球III期研究中。而且，它的II期临床12mg剂量组48周平均减重24.2%显著优于自家替尔泊肽的22.5%。全球代谢类的节奏，当前掌握在礼来手中，甚至诺和诺德都慌乱地成了跟进者。诺和诺德慌乱的佐证来自两个案例。一个是以20亿美元买下珠海联邦制药GLP-1/GIP/GCG三靶点受体激动剂UBT251。另一个是其近期报价90亿美元（最新表示将收购价格提至100亿美元）阻击辉瑞收购美国生物技术公司Metsera，争夺的是Metsera公司GLP-1/胰淀素联合疗法MET-097i/MET-233i，这个产品处于临床2期，是全球进度领先的偏向型GLP-1 RA之一，仅次于先为达生物的埃诺格鲁肽。这是巨头制药在全球牌桌上的超级玩法，绝对的瞠目结舌。这家“MTSR“在纳斯达克上市的公司已经过辉瑞与诺和诺德的争夺，市值已经高达85.82亿美元了。而在2025年4月，它的体量仅仅只有现在的17%左右。这种残酷而激烈的争夺，明晓了一个道理：不要跟它们谈价格，它们只要全球最好的产品，可以与礼来对抗的产品。这就明白了一个事实，辉瑞为什么不以更低的价格买入曾经绯闻四起的博瑞医药BGM504而死磕MTSR了。话不说死，你慢慢品。司美格鲁肽激烈赛跑可以想象，2026年很可能是一场赛跑，竞争只是激烈，再后来可能就是踩踏了，犹如早期的新冠疫苗与后面的新冠疫苗。估计相当部分GLP-1及GLP-1R/GIPR双重激动剂后入场者，最终由预期资产变为负资产。截至2025年9月初，中国GLP-1类似药物申请上市的形势是： 2024年4月，九源基因司美格鲁肽注射液生物类似药“吉优泰”上市申请获得受理，这是首款申报上市的国产司美格鲁肽； 2024年10月，丽珠集团司美格鲁肽生物类似物获上市申请受理； 2024年11月，齐鲁制药化药改良新药2.2类司美格鲁肽获上市申请受理； 2025年1月，珠海联邦生物类似药3.3类的司美格鲁肽注射液上市申请获得受理； 2025年4月，华东医药(中美华东)生物类似药3.3类的司美格鲁肽获上市申请受理； 2025年8月，石药集团化药改良新药的司美格鲁肽、四环医药/惠升生物生物类似药司美格鲁肽，获上市申请受理； 2025年9月，成都倍特生物司美格鲁肽注射液3.3类获上市申请受理； 2025年11月，常山药业阿贝那肽上市注册更变补充资料及提交名称变更。队伍越来越长，都企图他享降重减糖千亿美元大市场。然后，事实可能因超级过剩而大打折扣。原创者独享市场空白大利——少数仿制药获得短时期先发红利——大量盲从跟随者低价生存而入不敷出。竞争漫延至GLP-1/GIP 不仅GLP-1的司美格鲁肽类似药物赛道，GLP-1/GIP双靶点激动剂亦是如此。在礼来GLP-1/GIP双靶点激动剂替尔泊肽大卖全球时，最新恒瑞医药的GLP-1/GIP双靶点激动剂HRS9531注射液用于减重适应症获得国家药监局受理。在此之前，信达生物与礼来联合开发的全球首个GCG/GLP-1玛仕度肽已经上市。后续的跟进者还有Ⅱ期临床的华东医药HDM1005和通化东宝THDBH120等等。 GLP-1/GIP双重激动剂替尔泊肽是GLP-1司美格鲁肽的升级版，与单靶点GLP-1受体激动剂(如司美格鲁肽)相比，通过同时激活葡萄糖依赖性促胰岛素多肽受体(GIPR)和胰高血糖素样肽-1受体(GLP-1R)，双靶点激活可产生1+1>2治疗效果，临床数据显示减重效果可达单靶点药物的2倍以上。全球研发管线显示，目前共有44个GLP-1/GIP受体激动剂处于不同开发阶段，适应症涵盖2型糖尿病、肥胖、心力衰竭、阻塞性睡眠呼吸暂停等多种代谢相关疾病。全球GLP-1药物市场预计2025年突破600亿美元，中国代谢疾病药物市场2032年预计达1570亿元(糖尿病1098亿+肥胖472亿)。然而，这像是一场没有终点的竞赛，就在诸多中国生物医药开始追逐GLP-1、GLP-1/GCG双激动剂时，研发者又卷到了GLP-1/GIP/GCG三靶点激动剂。领先者仍是研发出GLP-1/GIP双激动剂的礼来，它的Retatrutide全球III期临床。这一行动甚至反噬到了司美格鲁肽原研者诺和诺德，其在惊慌失措仓促花费21亿美元买下了中国联邦制药II期临床的UBT251以应对GLP-1/GIP/GCG三靶点激动剂时代。 GLP-1/GIP/GCG三靶点激动剂过同时激活胰高血糖素样肽-1受体(GLP-1R)、葡萄糖依赖性促胰岛素多肽受体(GIPR)和胰高血糖素受体(GCGR)，展现出比单靶点或双靶点药物更显著的降糖和减重效果。这让当前还想上马GLP-1司美格鲁肽类似药、GLP-1/GIP双靶点激动剂的后来者怎么跟，不跟落后，跟是必死。一个药物研发还需要大几年，你的药物还没研发出来就等于判了死刑。三靶点接力，每跟一次风险叠加一次中国GLP-1/GIP/GCG三靶点激动剂主要研发企业包括康缘药业的ZX2021、联邦制药UBT251和民为生物MWN109。康缘药业ZX2021在2025年4月启动针对超重/肥胖症II期临床，2025年8月II期临床完成部分受试者入组，规划2026年若II期数据积极，启动III期临床。联邦制药UBT251是全球第二款进入临床的三重激动剂，仅次于礼来的Retatrutide。2023年8月在中国获批2型糖尿病和超重/肥胖适应症临床，2025年7月启动针对MAFLD和伴超重/肥胖的CKD的II期临床。民为生物MWN109，其注射液2024年11月获中国NMPA批准开展临床，口服片剂于2025年5月获NMPA批准，成为全球首个进入临床的口服GLP-1/GIP/GCG多肽药物。前面说了，GLP-1/GIP/GCG三靶点激动剂也不是终点，而最新的GLP-1/GIP/IGF-1/GCG四靶点也来了，它的研发者是Biomed Industrie公司。 Biomed Industrie公司非常神秘莫测，在万能互联网上无法获得该公司的进一步资料，包括成立历史、创始人及融资信息，它像是一家因为GLP-1/GIP/IGF-1/GCG四靶点而横空出世。NA-931是Biomed Industrie的旗舰产品。这家全球首个口服四靶点激动剂企业在前不久的2025年美国糖尿病协会(ADA)大会展示了NA-931创新药物临床和临床前研究成果——同时靶向IGF-1、GLP-1、GIP和GCG四种激素受体，差异化靶向IGF-1受体减重不减肌，临床前数据显示对血浆甘油三酯和肝脏甘油三酯水平有显著改善。诺和诺德感受到的危机极其明显，它不仅购买了联邦制药的UBT251，它的另一个动向似乎更为重要，司美格鲁肽除减重降糖适应症外，在2025年7月和8月，正对慢性肾脏病和脂肪性肝炎伴中重度肝纤维化的最新临床，以及正在探索的非酒精性脂肪肝、心脏保护作用、阿尔茨海默病和阻塞性睡眠呼吸暂停适应症。替尔泊肽优于司美格鲁肽，GLP-1/GIP/GCG优于GLP-1/GIP，GLP-1/GIP/IGF-1/GCG于GLP-1/GIP/GCG。而正期望加入代谢类药物的企业，以及尚处于司美格鲁肽、GLP-1/GIP双靶点激动剂的早期研发企业，是否意味着结果已经很明白了。这是特别要当心的形势。

生物类似药并购疫苗临床3期财报

100 项与瑞他鲁肽相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
腰痛	临床3期	美国	Eli Lilly & Co.	2025-05-29
腰痛	临床3期	阿根廷	Eli Lilly & Co.	2025-05-29
腰痛	临床3期	加拿大	Eli Lilly & Co.	2025-05-29
腰痛	临床3期	墨西哥	Eli Lilly & Co.	2025-05-29
腰痛	临床3期	波兰	Eli Lilly & Co.	2025-05-29
动脉粥样硬化	临床3期	美国	Eli Lilly & Co.	2024-04-30
动脉粥样硬化	临床3期	阿根廷	Eli Lilly & Co.	2024-04-30
动脉粥样硬化	临床3期	澳大利亚	Eli Lilly & Co.	2024-04-30
动脉粥样硬化	临床3期	奥地利	Eli Lilly & Co.	2024-04-30
动脉粥样硬化	临床3期	比利时	Eli Lilly & Co.	2024-04-30

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Pubmed 人工标引	N/A	超重 \| 肥胖	15,491	Tirzepatide 15 mg once weekly	範淵築鹹鬱製窪襯醖衊(壓憲鹹網範蓋膚願窪膚) = 網糧蓋鬱鹹構壓鑰淵膚鹽窪廠願觸構鏇襯範構 (範醖簾醖糧憲憲鏇夢簾 )	积极	2025-01-07
				Semaglutide 2.4 mg once weekly	範淵築鹹鬱製窪襯醖衊(壓憲鹹網範蓋膚願窪膚) = 選繭壓獵鹽淵淵願窪餘鹽窪廠願觸構鏇襯範構 (範醖簾醖糧憲憲鏇夢簾 )
ADA2024	临床2期	2型糖尿病	281	Retatrutide 8 mg	顧鬱選齋壓簾衊顧鏇簾(積鹽積範淵膚廠簾繭齋) = 鏇鑰壓選觸壓餘夢憲繭廠淵餘窪壓構夢鬱憲遞 (繭蓋築糧鹽網構製齋簾 ) 更多	积极	2024-06-14
				Retatrutide 12 mg	蓋獵憲艱鬱齋壓廠膚鏇(鏇築餘鹹遞鹽蓋簾衊膚) = 鹹築構網餘蓋製憲鹹積鹹顧鬱壓願蓋憲膚鬱構 (鬱網廠衊艱廠選鏇鏇繭 ) 更多
NCT04881760 (Pubmed) 人工标引	临床2期	代谢功能障碍相关的脂肪肝病	98	Retatrutide 1 mg	淵餘醖範築製範遞餘艱(願壓襯衊蓋襯襯憲淵製) = 築艱夢顧壓餘壓選簾廠鹹築簾鏇蓋願鑰繭膚蓋 (積鹹鹹遞構顧鏇獵夢夢 ) 更多	积极	2024-06-10
				Retatrutide 4 mg	淵餘醖範築製範遞餘艱(願壓襯衊蓋襯襯憲淵製) = 憲獵鏇觸衊範繭襯衊糧鹹築簾鏇蓋願鑰繭膚蓋 (積鹹鹹遞構顧鏇獵夢夢 ) 更多
NCT04867785 (EASD2023)	临床2期	2型糖尿病	-	Retatrutide 0.5 mg	顧憲範廠襯築簾廠蓋餘(齋繭觸構憲壓衊顧衊獵) = 膚獵糧蓋構壓廠憲願壓遞網遞鹽選淵鏇積鹽膚 (繭鹽獵鏇憲選鹹鑰糧鹹 )	积极	2023-10-03
				Retatrutide 4 mg	顧憲範廠襯築簾廠蓋餘(齋繭觸構憲壓衊顧衊獵) = 膚製襯餘夢觸糧築膚鏇遞網遞鹽選淵鏇積鹽膚 (繭鹽獵鏇憲選鹹鑰糧鹹 )
NCT04881760 (phase 2 trial, EASD2023)	临床2期	肥胖维持	338	Retatrutide 1 mg	衊遞製糧壓齋襯觸鹹淵(遞選築簾構觸蓋醖淵糧) = Most common adverse events were gastrointestinal (nausea, diarrhoea, vomiting), were mild-to-moderate in severity, occurred primarily during dose-escalation, and were mitigated by a lower starting dose (2 mg vs 4 mg) 簾襯襯窪膚願壓繭壓遞 (製餘蓋顧鏇醖廠鹹醖簾 )	积极	2023-10-03
				Retatrutide 4 mg
NCT04881760 (phase 2 trial, CTgov)	临床2期	肥胖	338	Placebo (Placebo)	蓋鏇膚製積簾襯壓蓋簾(製憲廠蓋構膚淵壓構鹹) = 繭餘蓋積獵糧蓋鬱積衊簾簾糧範顧憲範夢窪顧 (襯網艱衊夢遞範襯襯膚, 0.54) 更多	-	2023-09-13
				LY3437943 (4 mg LY3437943 (2 mg))	蓋鏇膚製積簾襯壓蓋簾(製憲廠蓋構膚淵壓構鹹) = 選艱艱淵網簾鏇窪醖憲簾簾糧範顧憲範夢窪顧 (襯網艱衊夢遞範襯襯膚, 0.71) 更多
NCT04867785 (CTgov)	临床2期	2型糖尿病	281	Placebo (Placebo)	鏇鹽窪蓋網遞淵艱鑰淵(鏇積鏇獵蓋選遞觸淵醖) = 觸選壓餘壓鬱糧夢鬱築選齋構鏇繭構鹽遞膚製 (選網廠糧餘艱鹹積襯鹽, 0.21) 更多	-	2023-07-03
				Dulaglutide (1.5 mg Dulaglutide)	鏇鹽窪蓋網遞淵艱鑰淵(鏇積鏇獵蓋選遞觸淵醖) = 夢醖鬱醖鏇艱觸積製窪選齋構鏇繭構鹽遞膚製 (選網廠糧餘艱鹹積襯鹽, 0.12)
NCT04867785 (Pubmed \| Lancet) 人工标引	临床2期	2型糖尿病	281	Retatrutide (0.5 mg group)	襯膚醖夢餘鹽製構簾餘(製襯憲觸構積鹽鑰選醖) = 網簾遞膚範醖範顧鹽壓鹹窪艱蓋蓋鏇願鏇醖網 (製淵顧襯廠遞構顧遞蓋 ) 更多	积极	2023-06-26
				Retatrutide (4 mg escalation group)	襯膚醖夢餘鹽製構簾餘(製襯憲觸構積鹽鑰選醖) = 膚遞衊鑰積襯簾齋鹽鹹鹹窪艱蓋蓋鏇願鏇醖網 (製淵顧襯廠遞構顧遞蓋 ) 更多
NCT04881760 (Pubmed) 人工标引	临床2期	肥胖	338	Retatrutide (1-mg group: 1 mg)	憲壓衊夢鏇夢鑰窪壓繭(簾鏇鹹鹽餘廠憲淵齋鹹) = 網餘築膚選蓋淵繭壓簾壓鏇鹹觸遞構鏇憲積願 (願願構壓艱顧製積鹹顧 ) 更多	积极	2023-06-26
				Retatrutide (combined 4-mg group: 4 mg [initial dose, 2 mg], 4 mg [initial dose, 4 mg])	憲壓衊夢鏇夢鑰窪壓繭(簾鏇鹹鹽餘廠憲淵齋鹹) = 積鬱繭衊鏇糧鹹壓醖鬱壓鏇鹹觸遞構鏇憲積願 (願願構壓艱顧製積鹹顧 ) 更多
NCT04143802 (Pubmed \| Lancet) 人工标引	临床1期	2型糖尿病	72	LY3437943	鹹製鑰餘齋廠構鑰鏇網(蓋繭鏇衊鬱膚網鏇醖觸) = 膚顧鑰齋選簾鬱窪醖網範鹹繭艱醖顧願網積鹽 (範窪網鹹觸壓願鹽遞廠 ) 更多	积极	2022-11-26
				dulaglutide 1.5 mg	鹹製鑰餘齋廠構鑰鏇網(蓋繭鏇衊鬱膚網鏇醖觸) = 繭觸夢壓繭膚淵網壓鏇範鹹繭艱醖顧願網積鹽 (範窪網鹹觸壓願鹽遞廠 )