Retatrutide

创新药管线出海，股价却遭大跌，二级市场那么不讲道理？ 2025年3月24日，联邦制药宣布与诺和诺德达成出海协议。后者获得前者GLP-1/GIP/GCG（GGG）受体激动剂UBT251的大中华区外全球权益，前者获得2亿美元预付款、18亿美元里程碑金额，以及一定比例的销售分成。 本应皆大欢喜，联邦制药股价却于次日下跌12%。利好变为利空，不少散户直呼“看不懂”、“炒短线变成了炒洋芋（穷了Orz）”。 “利多”变“利空” 不是“20亿美元交易”不够吸引人，而是联邦制药发布了2024年全年报。2024年，联邦制药全年营收约137.59亿元，同比增长0.1%。 其中，中间体、原料药、制剂业务分别上升1.8%、下降0.5%及下降5.9%，分部溢利同比分别上升5.9%、下降9.8%及下降47.0%。中间体与原料药属于联邦制药的传统业务，构成了公司营收大头。而制剂业务的大幅下滑，主要与国家集采导致的价格下调有关。 此外，2024年联邦制药的制剂产品研发费用同比增长了26.6%，达5.772亿元。近几年，联邦制药布局了近20项1类新药，自免、眼科、抗感染和内分泌等多个领域。其中，UBT251便是其创新标杆之一。 简单而言，就是年报停滞抵消了GLP-1出海的想象空间。 联邦制药是一个颇有年头的公司，1990年成立，2007年香港上市。与多数本土老牌药企类似，最初通过中间体、原料药起家，后续转型做起了制剂业务，包括人用抗生素类、胰岛素类、动保等板块。 这家药企的特点就是基本盘稳固，营收能力也较为稳健，特别是近年来随着胰岛素业务的增长（国内市场与甘李、通化东宝或为同在第一梯队）。2022年以来，联邦制药股价一直呈上升趋势，此次纵然有20亿美元交易铺垫，股价依旧大跌，可能是获利盘叠加年报停滞再叠加恐慌盘所致。 图片来源：雪球 值得一提的是，或许市场仍将联邦制药视为原料药企业，估值并不高，截止日前公司港股市值不过300亿元，尤其是对比港股上市药企与多数Biotech，联邦制药的盈利能力较为可观的情况下。 早有“定数”的出海交易 此次交易，早有定数。虽然现在下定论，像是“马后炮”。 当诺和诺德下一代CagriSema（司美格鲁肽+Amylin类似物cagrilintide的复方制剂）三期数据读出时，这笔交易便有了达成的前提条件。 药时代在《36周减重22%！又一重磅GLP-1产品公布临床结果，2025年还有哪些减重产品值得期待？》一文中提到，诺和诺德面对礼来替尔泊肽施压，可用的底牌中高剂量Wegovy”与“CagriSema”双双市场未达预期，外加司美格鲁肽被纳入美国Medicare新一轮价格谈判，诺和诺德需要“找补”，需要继续卷。 此外，礼来手中除了已上市的替尔泊肽，GGG三重激动剂Retatrutide对诺和诺德的“威胁”最大，该药物是替尔泊肽的迭代产品，疗效或更优，48周减重幅度达24.2%。据不完全统计，全球布局GGG三重激动剂的药企并不多，目前进入临床在研共5款。 图片来源：创药网 礼来的Retatrutide已在全球开展9项三期临床；韩美的HM15211/efocipegtrutide在MASH的二期临床，HM15275单药在一期临床；民为生物的MWN109也在临床一期；然后就是联邦制药的UBT251，已完成一期研究并与近期开展了II期研究（减重与降糖）。 其中，韩美GLP-1类药物的技术路径存在风险。此前，韩美与礼来、勃林格殷格翰、赛诺菲、强生的多项合作均以失败告终。鉴于此，2020年默沙东引进韩美GLP-1/GCG双靶点激动剂HM12525A的权益，预付款仅1000万美元，且主攻非酒精性脂肪性肝炎（NASH）领域。 然后，UBT251脱颖而出。一是临床数据不错，早期DIO小鼠模型研究显示，UBT251的总体减重效果不亚于礼来的Retatrutide；1a期数据显示，1.0~4.5mg剂量范围内，受试者体重较基线明显下降，最大降低幅度（Emax）平均值范围 为-3.19~-4.80kg，明显优于安慰剂组；1b期数据显示，在最高剂量组中（1mg/3mg/6mg），完成试验的受试者平均体重较基线下降15.1%，而安慰剂组受试者的平均体重较基线增加1.5%。 图片来源：华创证券医药团队（2024-12-21） 二是联邦制药估值偏低，其创新管线估值或许存在较大的“压价”空间。 最后，就是UBT251中美两地临床可以同步开展。目前，UBT251已在中国获批开展针对成人2型糖尿病、超重或肥胖、代谢相关脂肪性肝病（MAFLD）和慢性肾脏病（CKD）的临床试验，并在美国获批开展针对成人2型糖尿病、超重或肥胖以及慢性肾脏病（CKD）的临床试验。 所以说，这笔交易早有定数。当初，礼来用替尔泊肽头对头司美格鲁肽；现在，诺和诺德选择用UBT251对标Retatrutide，直接“硬刚”。 小结： GLP-1无疑是划时代的靶点，其代谢领域地位，等同于肿瘤领域的PD-1，因此该靶点内卷严重。 在一众MNC中，礼来、诺和诺德呈双寡头格局半分天下；罗氏、安进尝试再卷一卷多靶点；默沙东另辟蹊径，寻找其他差异化适应症；阿斯利康选择与CVRM（心血管、肾脏及代谢）业务线的其他管线做联合用药…… 大家都在“卷”，但各有各的卷法。而MNC的一举一动，无疑将对国内药企产生巨大影响，无论是竞品公司的商业活动，亦或是看似不相关的临床数据读出。 参考资料： 1.联邦制药官网 2.雪球 3.【迷雾01】联邦制药 3933——Novo Nordisk大跌的最大受益者？（TruTheMist） 4.一图看清GLP-1RA减重数据20241221（华创新药） 5.GLP-1/GCG/GIP三重受体激动剂研究进展（创药网） 6.其他公开资料 图片来源：pixabay 481款！2024年FDA孤儿药认证大爆发！中国排名第二 2025-03-24 阿斯利康2025中国宏图：不止和铂，还有...... 2025-03-22 股价暴跌41%！Elevation终止石药ADC的海外开发 2025-03-21 版权声明/免责声明 本文为原创文章。 本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。 文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。 如有任何问题，请与我们联系。 衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击这里，查看更多精彩!

Novo Nordisk is expanding its prospects in obesity and other metabolic disorders by securing rights to an early-clinical engineered peptide whose effects comes from activating three receptors — the same three targets hit by a next-generation weight drug in development by rival Eli Lilly. According to deal terms announced Monday, Novo Nordisk is paying United Biotechnology $200 million up front for global rights to its drug, UBT251. United Biotechnology retains rights to the molecule in China, Hong Kong, Macau, and Taiwan. The Gaungdong, China-based company could receive up to $1.8 billion in milestone payments, plus royalties from sales if Novo Nordisk commercializes UBT251. Novo Nordisk has the market’s top-selling obesity drug in Wegovy, a product whose main ingredient is a peptide engineered to mimic the hormone that activates the GLP-1 receptor. R&D efforts across the pharma industry are trying to expand this approach to multiple targets. Novo Nordisk’s pipeline includes clinical-stage drugs that hit two targets. UBT251 gives the Danish pharmaceutical giant a once-weekly injection that hits three: GLP-1, GIP, and glucagon. According to Novo Nordisk and United Biotechnologies, preclinical testing of this long-acting peptide showed potent activity on all three receptors. presented by Health Tech The 5 Best Software to Buy for Managing a Spa Franchise Choosing the right software translates directly into better client management, operational efficiency and growth for your spa franchise. Discover which tool is best for your business. By Meevo Under United Biotechnology, UBT251 recently completed double-blind, placebo-controlled Phase 1b clinical trial in China. The 12-week study enrolled 36 participants randomly assigned to three different dose groups. In the highest dose group, the companies said the weight of those who completed the trial decreased by an average 15.1% from baseline. By comparison, the average weight in the placebo group increased 1.5% from baseline. The companies said the most common adverse events were gastrointestinal, which is consistent with other obesity medications. These events were characterized as mild to moderate in severity. “The addition of a candidate targeting glucagon, as well as GLP-1 and GIP, will add important optionality to our clinical pipeline, as we look to develop a broad portfolio of differentiated treatment options that cater to the diverse needs of people living with these highly prevalent diseases,” Martin Holst Lange, executive vice president for development at Novo Nordisk, said in a prepared statement. “We look forward to building on United Biotechnology’s scientific work and further exploring the potential best-in-class properties of UBT251 across cardiometabolic disease indications.” In China, UBT251 is being developed for type 2 diabetes, overweight or obesity, metabolic dysfunction-associated fatty liver disease, and chronic kidney disease. The drug is cleared to enter clinical testing in the U.S. in type 2 diabetes in adults, overweight or obesity, and chronic kidney disease. Lilly’s candidate to activate the GLP-1, GIP, and glucagon receptors is an engineered peptide named retatrutide. Acknowledging the caveats that come with cross-trial comparisons, Phase 2 results of this weekly injectable drug showed an average 17.5% reduction in body weight from baseline measured after 24 weeks. After 48 weeks, the average weight reduction was 24.2%. Sponsored Post A Data-Driven Guide to Patient Access Success A new report from Relatient, A Data-Driven Guide to Patient Access Succes, highlights how focusing on data accuracy and relevance can enhance the performance of healthcare practices. By Relatient Novo Nordisk’s deal for the United Biotechnology drug gives it another try at drugging three targets in single metabolic drug. In a note sent to investors, William Blair analysts noted that the pharma giant discontinued development of a triple agonist for chronic weight management in 2020 due to the company’s clinical success from pairing Wegovy and cagrilintide, a peptide engineered to target the amylin receptor. Also, the triple agonist did not reach the desired target profile. Mid-stage data posted by Lilly’s retatrutide in 2023 revived interest in obesity drugs that hit three targets, the William Blair analysts said. But retatrutide’s results also showed more severe and frequent adverse events compared to approved drugs, such as Lilly’s own Zepbound. These side effects include higher measures of hypersensitivity, antidrug antibodies, and cardiac arrhythmia. Retatrutide’s results to date leave an opportunity for companies developing triple-acting obesity drugs to differentiate on safety. That said, William Blair believes dual-acting obesity drugs offer the broadest clinical utility. Triple agonists could benefit patients with high body mass indexes. Retatrutide is expected to post preliminary data in obesity and type 2 diabetes in 2026. There are other companies developing drugs that hit GLP-1, GIP, and glucagon receptors to trigger weight loss. Kailera Therapeutics launched last fall with $400 million and four in-licensed Jiangsu Hengrui Pharmaceuticals drug candidates, including one that hits those three targets. The pipeline of Metsera, which raised $275 million from its IPO last month, includes a long-acting peptide engineered to bind to and activate the three targets. Novo Nordisk Expands Discounted Wegovy Price to Brick-and-Mortar Pharmacies When Novo Nordisk earlier this month unveiled a discounted price for Wegovy available to eligible patients who order through a new online pharmacy, the drugmaker said this lower price would expand “in the near future” to those who use traditional pharmacies. That change is happening now. Novo Nordisk said Monday that all cash-paying patients who use Wegovy will be able to obtain the once-weekly injectable obesity drug from brick-and-mortar pharmacies for $499 per month, the same price for the drug through its new NovoCare online pharmacy, which ships the drug directly to patients’ homes. That price is a steep discount from the $1,349 list price for a month’s supply of the drug, a product administered in single-use, pre-filled injection pens. The new lower cash price for Wegovy covers all doses of the drug. As with the online offering, discounted Wegovy is available to uninsured patients who pay cash for their medicines as well as insured patients whose coverage does not include obesity drugs. Novo Nordisk said this updated offer replaces a previous savings offer that provided Wegovy to cash-paying patients for $650 per month. Patients who are enrolled in Medicare or Medicaid are ineligible for these offers. Novo Nordisk’s launch of lower-cost Wegovy followed Eli Lilly’s direct-to-consumer move with its obesity drug, Zepbound. Last summer, Lilly announced eligible cash-paying patients could obtain Zepbound through the company’s digital health platform, LillyDirect. The discounted offerings for cash-pay patients give both Lilly and Novo a way to keep market share from going to compounding pharmacies. Compounding pharmacies may sell their version of a marketed drug when that product is in shortage. Compounded drugs are not tested in clinical trials, nor are they approved by the FDA. With the FDA recently declaring shortages resolved for Zepbound and Wegovy, compounding pharmacies must stop selling their versions of these drugs, though they may continue to offer compounded drug if a patient needs a dose level unavailable in a branded product. Compounders are suing the FDA, claiming that shortages persist and the agency’s declarations that the shortages are over were done without due process. Both Lilly and Novo contend that offering their respective drugs directly to patients can avoid what they say are the safety risks of compounded drugs. But the new discounted prices for Wegovy and Zepbound are still higher than the prices of compounded versions.