Selonsertib

Not content with navigating Rezdiffra’s trajectory to blockbuster territory, Madrigal Pharmaceuticals has spent 2026 shopping for a range of drugs that the company hopes could work alongside its metabolic dysfunction-associated steatohepatitis (MASH) trailblazer. Madrigal kicked off the year paying $50 million to Pfizer for the rights to a DGAT2i inhibitor, before spending $60 million the following month on six preclinical siRNA programs from China’s Ribo Life Science and its Swedish subsidiary Ribocure Pharmaceuticals that Madrigal wants to use to silence genes implicated in MASH. The company explained at the time that both deals were aimed at securing therapies that could be combined with Rezdiffra. The biopharma was back at the dealmaking table in May, paying $25 million upfront to Arrowhead Pharmaceuticals for a phase 1-stage RNA interference therapeutic that had previously been rejected by Johnson & Johnson. Early clinical data had suggested the asset could reduce liver fat in a mutation found in 30% of MASH patients, including high prevalence in Hispanic populations. Combined with a preclinical GLP-1 agonist licensed from China’s CSPC Pharmaceutical for $120 million upfront last year, Madrigal now has a diverse array of MASH assets coming up behind Rezdiffra. So what’s the strategy behind this rapid pipeline expansion? “The question early on was what mechanisms we wanted,” Madrigal CEO Bill Sibold told Fierce in an interview at the company’s office in Waltham, Massachusetts. “My answer was: we want all of them,” Sibold continued. “We want anything that makes sense mechanistically or has proven already to have an effect on MASH.” It’s a sign of just how much Rezdiffra has changed the game since being approved as the first-ever treatment for MASH in 2024. Before that point, Sibold said he had counted 23 drugs across the industry that had failed to treat the fatty liver disease previously known as nonalcoholic steatohepatitis (NASH). This rollcall of failure meant MASH had become “the graveyard of drug development,” lumped in with other difficult-to-treat conditions like sepsis and lupus, he remembered. The disease occurs when fat builds up in the liver, causing inflammation and eventually cell death. It is the leading cause of liver transplants for women and the second biggest cause for men in the U.S. “Industry had been really interested in this area for a long time, but nobody could crack the nut,” Sibold said. Many companies tried and failed to find a breakthrough. Gilead’s ASK1 inhibitor selonsertib and its LOXL2 enzyme-targeting simtuzumab both flopped in the clinic, as did Genfit’s dual PPAR alpha/delta agonist elafibranor and Conatus Pharmaceuticals' pan-caspase inhibitor emricasan. Rezdiffra’s origins go back to Roche. Madrigal founder Rebecca Taub, Ph.D., left the Swiss pharma’s metabolic unit to work for VIA Pharmaceuticals, which licensed the thyroid hormone receptor (THR)-β agonist. Madrigal assumed the rights to that agreement when it was founded in 2011 and continued to develop the therapy. Sibold remembers getting a call from a recruiter about the Madrigal CEO position in 2023 while he was president for North America at Sanofi, having helped launch immunology blockbuster Dupixent. “There's no way I'm going to leave this to go to that,” he remembers of his initial reaction to the offer. But as Sibold dug into the company, educating himself on the trials and the science behind its lead asset, he became convinced that this was a unique opportunity to make a special impact. The year after Sibold joined up, Madrigal had secured Rezdiffra’s historic FDA approval. As well as the company's headquarters in West Conshohocken, Pennsylvania, the company now also has an office in Massachusetts—which Fierce visited—as well as an international outpost in Switzerland. “There were so many Big Pharma companies trying to solve [MASH], and this little Pennsylvania company of very few people had the tenacity, the guts and the grit to get there,” Sibold said. Madrigal reported $958.4 million in annual net sales for the drug in 2025. By the second quarter of this year, Rezdiffra was bringing in $364.3 million, equivalent to year-over-year growth of 71%. Sibold told Fierce that it wasn’t always this way. Early on, a MASH advocate told him: “We didn't know whether to believe you at first because it seemed like such a huge hill to climb that you guys didn't even have an approved product. But you are doing exactly what you said you would do.” After establishing itself as the market leader in MASH, what’s next? Does the company stay in its lane, expand into immunology targets or look at new indications? For Sibold, the answer lies in Madrigal’s five-word purpose: leading the fight against MASH. The biopharma wants to continue working with the MASH community it has come to know so well to build out its pipeline with more effective and comprehensive treatments for different subpopulations. Rather than generate data and hope to get bought by a bigger fish, Sibold said he is planning for an independent and sustainable company 10 to 20 years down the line. His vision is for MASH treatments to grow like other specialty markets, such as rheumatoid arthritis, psoriasis or inflammatory bowel disease, with dozens of products that generate tens of billions of dollars in annual sales. “We feel like MASH will emerge like that, and as a result, we want to have the portfolio of products that can best help all or subpopulations of patients,” Sibold said. Unlike a Big Pharma, where MASH may be one of a myriad of indications being focused on, Sibold suggested Madrigal's strength comes from the fact it is committed to the disease. This approach is reflected in trial enrollment and feedback, he said. “The community values expertise, and I think we've made a conscious decision to be experts in MASH,” he said. “Through expertise comes insight into what might be the next best mechanism, or the next best mechanism to combine with your current mechanism, or the best way to design the next trial.” Because reducing liver fat is so important to preventing or treating MASH, GLP-1s are moving into the space and posing a potential threat. Last year, Novo Nordisk’s Wegovy was approved to treat MASH, and some people have warned Sibold that Madrigal could be crushed by GLP-1s in the future. Instead, the CEO insisted more activity in the space is a good thing for Madrigal. “It's great to have another company who's putting resources into diagnosis, awareness and treatment,” he said. “There are some patients that are getting Wegovy, but it is helping to grow the market. It's not to our detriment.” But other Big Pharmas are circling. Last year saw GSK acquire the FGF21 analog efimosfermin from Boston Pharmaceuticals for $1.2 billion upfront, while Roche picked up a similar drug called pegozafermin as part of its $3.5 billion buyout of 89bio . Madrigal may be looking to become the MASH version of what Vertex Pharmaceuticals has achieved in cystic fibrosis, but that doesn’t mean Sibold and his team couldn’t eventually broaden their focus. “Would we look at other diseases? Yes. We would in time, or if the biology takes us there,” he told Fierce. But for now, the company is leaning into MASH specialization, developing relationships with patient groups, clinicians and researchers while raising Rezdiffra’s profile and growing a specialized portfolio of complementary therapies. “It's been fun. It's making a difference. It's helping patients,” Sibold said. “This is as good as it gets.

一款全球稀缺的抗肝纤维化大单品，正在重新被市场认识。 全球尚未有抗肝纤维化对症西药获批上市，THR-β激动剂Resmetirom虽然只获批了NASH/MASH适应症，却凭借“有抗纤维化疗效”这一卖点实现了商业化的快速起量。 但鲜有人注意到，在中国市场，百洋医药同样有一款中成药产品填补这一临床空白。 拆解百洋医药，可以发现处方药板块近年增速最快的品种是甘纤乐（扶正化瘀），2025年单年收入7.42亿元，同比增长17.53%，多年复合增速保持双位数。 不同于以往市场熟悉的迪巧这类OTC品牌业务，甘纤乐背后是另一套完全不同的价值逻辑：中药保护独家品种+循证壁垒TOP级的抗肝纤维化药物+抗肝纤维化品类份额第一。 很多人对中成药的印象是缺少扎实的临床证据，而甘纤乐用二十年循证积累、覆盖近4000名患者的研究数据，已经把价值逻辑和品种的稀缺性摆在了台面上。 从百洋医药目前120亿出头的市值可以看出，市场对百洋的认知仍然锚定“OTC钙剂龙头迪巧”的商业化平台公司形象上。自百洋医药收购百洋制药后，甘纤乐已成为公司自有品种，但在资本市场的定价中，这个品类冠军的价值几乎被完全忽视，其余创新管线品种的潜在价值同样未得到市场关注。 01 独家品种的坡长雪厚：西药全军覆没的赛道 + 7%渗透率 目前，全球还没有专门针对乙肝肝纤维化获批的西药。 这并不是“没人尝试去做”，而是“做不出来”。 过去几年，多家国际药企曾尝试突破肝纤维化治疗，但均以失败告终：吉利德的Selonsertib（ASK1抑制剂）三期失败；Intercept的奥贝胆酸因安全性问题被FDA拒批；法国Genfit的Elafibranor三期达不到终点直接放弃。至于2024年获批的Resmetirom，它针对的是NASH/MASH（代谢相关脂肪肝的纤维化），并不覆盖乙肝相关肝纤维化。 为什么做不出来？核心难点有三：一是肝纤维化的病理机制极其复杂，涉及多条信号通路交叉，单靶点策略很难奏效；二是临床金标准需要肝穿刺活检，患者招募困难、试验周期长、成本高昂；三是在抗病毒治疗已经压低了基础事件率的背景下，叠加新药的增量获益空间很难跑出统计学显著。 这种局面意味着什么？甘纤乐的竞争格局根本不是“中药 vs 西药”的纸面比较，而是“最高循证支持的药物 vs 完全空白”的品类独占。 再看市场基数。中国约7500万乙肝感染者，其中慢乙肝患者约2000-3000万人，在一项抽样研究中约38%存在显著性肝纤维化。据中康和IQVIA数据显示，2025年国内抗纤产品市场销售额已达24亿元，复合增速约16.8%。弗若斯特沙利文预计，到2031年国内抗肝纤维化治疗药物市场规模将达到8亿美元。 但巨大市场的核心矛盾在于：目前乙肝患者中使用抗纤药物的人数占使用抗病毒药的人数，仅约7%，93%的患者尚未接受抗纤治疗。 渗透率之所以这么低，是因为临床实践主要聚焦于“抗病毒”单药治疗。抗病毒药物（恩替卡韦、替诺福韦等）能阻断病毒复制，减轻新的肝损伤，但无法逆转已经形成的纤维化。打个比方：抗病毒是“扑灭明火”，抗纤维化是“清除余烬”，两者缺一不可。 未来，渗透率提升几乎是确定性的。2025年9月，国家疾控局联合多部门共同制定《中国防治病毒性肝炎行动计划(2025—2030年)》，要求至 2030年，慢性乙肝患者诊断率达80%及以上、治疗率80%，而中国当前仅24%和15%，基数放大空间巨大。更关键的是，乙肝背景下的肝纤维化若不干预，沿“肝炎→肝硬化→肝癌”链条进展的风险将大幅上升，每年或将有大量患者进展到肝癌。而“抗病毒+抗纤维化”的双抗治疗正在成为新的临床标准，甘纤乐早在2009年就最早提出并践行了这一理念。 按中性测算逻辑来看：抗纤维化品类渗透率实现翻倍，甘纤乐就是20亿规模品种。这是一个教科书式的长坡厚雪增长公式。 02 甘纤乐，坚不可破的临床证据链 在抗肝纤维化领域，甘纤乐的核心优势并非“中药身份”，而是其长期积累形成的循证体系。 甘纤乐拥有从“逆转纤维化”到“降低肝癌风险”的多重完整证据链，这在中成药品种中几乎独一无二。 第一重：十二五重大专项RCT——肝穿金标准证明“真能逆转纤维化、肝硬化” 甘纤乐疗效证据的基石，是一项由国家“十二五”科技重大专项支持的多中心RCT。研究在全国20家中心入组了648例慢乙肝肝硬化代偿期患者，一组用恩替卡韦+扶正化瘀（双抗组），一组只用恩替卡韦（单抗组），治疗48周。最关键的设计在于，治疗前后都做了肝穿刺病理分期，直接看组织学变化，而不是只看超声或血清学这类替代指标。 结果很清楚，双抗组的肝纤维化、肝硬化逆转率比单抗组高出14.6个百分点。这一高等级临床证据标准揭示了，在抗病毒的基础上加用甘纤乐，可以真正逆转肝纤维化、肝硬化，而不仅仅是改善几项血清学指标。 第二重：2020年北京地坛医院队列——首次证明“能降低肝癌风险” 如果说RCT证明了“逆转纤维化/肝硬化”，那接下来的问题是：这最终能不能转化为降低肝癌风险？2020年北京地坛医院发表的一项回顾性队列研究首次回答了这个问题。 研究纳入842例乙肝肝硬化患者，其中270例接受甘纤乐联合抗病毒治疗，572例仅接受抗病毒，用倾向评分匹配消除混杂后形成每组259例，观察了5年数据发现：联合组患者肝癌累计发生率只有10.0%，而对照组高达23.2%，联合用药组降低肝癌风险56.9%。 更有意思的是剂量-反应关系：用药12-36个月的患者HR （Hazard Ratio，风险比）降到0.28，用药超过36个月的患者HR只有0.04，几乎把肝癌风险压到了接近零。而且不管患者肝功能分级处于什么阶段，获益都是一致的。 第三重：2024年全国20中心多中心队列——大规模独立验证“实锤” 单中心的结果虽然亮眼，但其证据强度说服力有限。而甘纤乐2024年发表的一项多中心研究，给出了确定性更强的回答。 这一次，研究跨越8年时间（2013-2021），覆盖全国20家医院，初筛近1800例患者，匹配后每组231例。5年肝癌发生率：联合组9.8% vs 对照组21.8%，用药超过36个月的患者HR=0.216（P<0.01），和地坛医院的发现高度吻合。 这项研究还回答了一个关键的机制问题：两组患者的病毒学应答率（乙肝DNA转阴率）没有显著差异。这说明联合组肝癌风险的降低，不是因为“碰巧这组人病毒控制得更好”，这意味着获益确实来自抗纤维化本身，而非间接的抗病毒效应。 第四重：唯一在美国FDA完成II期临床的肝病类中成药 甘纤乐完成美国II期临床的意义，不仅在于试验结果本身，更在于它证明甘纤乐的制造工艺、质量控制和安全性达到了FDA体系可接受的水平。对于一款中成药来说，这是极高的门槛认证，为其“药品”而非“保健品”的定位提供了国际监管层面的背书。 从RCT证明逆转纤维化→两项大样本长随访队列证明降低肝癌风险→FDA质量体系认可，甘纤乐这样完备临床证据链，估计在国内中成药品种中找不到第二个。 更关键的是，政策东风在助推甘纤乐这样的好药。近期国务院批复了《中医药振兴发展“十五五”规划》（2026年7月10日发布），明确“加快推进中医药现代化”。甘纤乐恰恰是“循证中药”的标杆案例，其证据等级远超一般中成药品种。在顶层对中药现代化高度重视的政策东风下，这类拥有扎实临床数据的品种有望获得更优先的推广资源和医保支持，加速市场渗透。 03 为什么说甘纤乐价值被忽视？ 国内市场对独家、稀缺的中药品种历来给予较高估值溢价。片仔癀当前TTM PE约30倍，历史峰值曾达60-70倍；九典制药凭借独家品种2021-2023年平均PE在25倍以上。 （中药行业上市公司估值对比图） 与大部分处于业绩下行、估值收缩阶段的中药企业不同，百洋医药的甘纤乐正处于大展拳脚的上升期。甘纤乐2016年7月首次获批中药二级保护，2025年11月保护期延长至2030年7月，后续有望进一步延续。 过去，市场将甘纤乐这个品种包裹在百洋医药OTC品牌的业务体系内，导致投资者未能洞悉其独立价值。 基于乙肝患者中使用抗纤中药的患者渗透率提升的保守、中性和乐观三种假设情形，假定利润率为25%、给到PE估值倍数为15倍-25倍，对应保守和中性情形收入分别为10-12亿和18-20亿，对应业务估值50-75亿和67.5-75亿。 目前百洋医药总市值约130亿。即便按极度保守的15倍行业市盈率估算中性情景，仅甘纤乐一个品种的独立价值就接近公司整体市值的50-60%。 这意味着什么？百洋医药其它资产组合：迪巧（年收入20亿的进口钙品类第一品牌）、纽特舒玛（进口纯乳清蛋白第一品牌，2025年增速39.65%）、创新投资布局（ZAP-X放疗机器人、北海康成、华昊中天、思合基因、济坤医药等肿瘤、抗纤维化赛道），这一揽子既有成熟品种稳定贡献利润、又有大量创新前沿品种的资产包集合，当前隐含估值仅在50-60亿之间。 对于一个既有稳定贡献现金流的品牌产品，又有多个创新投资标来说，这显然存在严重的市场价值错配。 不过，估值催化正在密集到来，仅甘纤乐就有：国家重大专项的参与、“十五五”中医药规划的政策东风、甘纤乐每个季度持续验证的双位数增速等催化，还不算公司其他创新资产未来的一系列里程碑。当市场渗透率从7%开始加速抬升，市场始终要对甘纤乐这个稀缺品种独立定价。 结语：最好的价值发现，往往藏在市场认知的错配里。 百洋医药正从商业化平台向创新转型，现阶段管线转化成效仍有待持续验证，甘纤乐则为公司开辟了一条差异化成长主线：西药全球空白的赛道里的品类冠军、7%渗透率的结构性提升、在中成药中独一无二的循证证据链条、以及国家重大专项的最新加持。 这不是一个概念，而是一个有数据、有壁垒、有增速验证的“隐形冠军”。而百洋医药作为背后的操盘手，其也终将会迎来真正的价值发现。 信息来源：瞪羚社 往期推荐 ! 免责声明 “汇聚南药”公众号所转载文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请在留言栏及时告知，我们会在24小时内删除相关信息。 本平台不对转载文章的观点负责，文章所包含内容的准确性、可靠性或完整性提供任何明示暗示的保证。  喜欢的点个“看一看”和"喜欢"吧 不然微信推送规则改变，有可能每天都会错过我们哦~