Efimosfermin alfa

设为【★星标】⭐了解更多养肝护肝知识 代谢功能障碍相关脂肪性肝炎（MASH）是一种日益严峻的全球健康问题。 这种疾病源于肝脏内脂肪的异常堆积，继而引发持续的炎症反应、肝细胞损伤，并最终导致肝纤维化。随着病程的推进，患者进展为肝硬化、肝功能衰竭甚至肝癌的风险显著升高。 然而，长期以来，针对MASH的有效治疗手段极为匮乏，临床对新疗法的需求迫在眉睫。 在此背景下，成纤维细胞生长因子21（FGF21）因其在调节能量代谢、改善脂肪变性和抗炎方面的多重生物学效应，成为MASH药物研发的热门靶点。 近日，国际顶级医学期刊《柳叶刀》发表了一项关于新型FGF21类似物的2期临床研究成果，为该领域注入了新的希望。 研究聚焦 靶向代谢与纤维化的创新疗法 本次研究的主角是一种名为 Efimosfermin alfa 的在研药物。 作为一种长效FGF21类似物，它被设计为每月仅需皮下注射一次，旨在通过模拟人体自身的FGF21功能，调节多条关键的代谢通路，从而达到减少肝脏脂肪堆积、缓解炎症并逆转肝纤维化的目的。 凭借其出色的药代动力学特性和治疗潜力，该药被业界视为潜在的“同类最佳”（best-in-class）候选药物。 临床试验设计 严谨验证安全性与有效性 这项发表在《柳叶刀》上的研究是一项多中心、随机、双盲、安慰剂对照的2期临床试验，旨在评估Efimosfermin alfa在目标患者群体中的疗效与安全性。 受试者人群：研究共招募了84名经肝活检确诊为MASH，且伴有2期（F2）或3期（F3）肝纤维化的患者。入组标准严格，要求患者年龄在18至75岁之间，体重指数（BMI）不低于27 kg/m²。 分组与治疗：患者被按照1：1的比例随机分配至两组。试验组（43人）接受每4周一次、剂量为300mg的Efimosfermin alfa皮下注射；对照组（41人）则接受等频率的安慰剂注射。整个治疗周期为24周。 关键数据解读 肝脏组织学与影像学的双重获益 研究结果显示，Efimosfermin alfa在多个关键疗效终点上均展现出优于安慰剂的显著效果： 肝纤维化逆转与MASH缓解 纤维化改善：在第24周，试验组中有45% 的患者实现了肝纤维化至少改善一个等级，且MASH没有出现恶化，而安慰剂组这一比例仅为21%，组间差异具有统计学意义（P=0.038）。这表明该药物具备直接逆转纤维化进程的潜力。 MASH缓解：在实现MASH缓解（即炎症消退）且纤维化未恶化的患者比例上，试验组更是达到了68%，远超安慰剂组的29%（P=0.002），显示出强大的抗炎活性。 肝脏脂肪含量的显著下降 脂肪分数大幅降低：通过MRI-PDFF技术评估，在第28周时，试验组中肝脏脂肪含量相对降低超过50%的患者比例高达50%，而安慰剂组仅为6%（P＜0.001）。 肝脏脂肪正常化：更令人鼓舞的是，试验组有32% 的患者实现了肝脏脂肪的完全正常化（脂肪含量≤5%），而安慰剂组仅有3%（P=0.003）。 安全性评估 耐受性良好，未见严重不良事件 在安全性方面，Efimosfermin alfa表现出了良好的耐受性： 不良事件 试验组和安慰剂组的不良事件发生率分别为67%和55%。绝大多数为轻中度，最常见的是胃肠道反应（如恶心、腹泻和呕吐）。 严重不良事件 试验组报告了两例严重不良事件（胃炎和胆道绞痛），但经研究者评估，其中胃炎事件与治疗药物无关。研究期间未发生3级及以上严重不良事件，也无死亡病例。 研究结论指出，在24周的治疗期内，Efimosfermin alfa的安全性特征与其他FGF21类似物基本一致，未发现新的安全性信号，也未对患者的生命体征或实验室指标产生具有临床意义的负面影响。 前景展望 迈向更大规模的临床验证 综上所述，这项2期临床研究证实，每月一次的Efimosfermin alfa在治疗伴有中重度肝纤维化的MASH患者时，不仅能够显著改善肝脏脂肪变性、炎症和纤维化，而且具备良好的安全性和耐受性。 《柳叶刀》刊发的这项研究为Efimosfermin alfa的后续开发提供了强有力的数据支持。它不仅在关键的肝脏组织学终点上取得了突破，更在影像学替代指标上展现了压倒性的优势。 目前，该药物的疗效和安全性仍需在更大规模、更长随访周期的3期临床试验中进行进一步验证，但其展现出的潜力无疑为全球数以亿计的MASH患者带来了一种全新的、极具前景的治疗选择。 四川省脂肪肝高血脂健康管理中心 随着脂肪肝发病率的逐年上升，这一健康问题已成为社会关注的焦点。 为积极应对这一趋势，四川华西肝病研究所正式成立了“四川省脂肪肝高血脂健康管理中心”，致力于为脂肪肝和高血脂患者提供全方位的健康管理服务。 中心集治疗、预防与健康知识普及于一体，开通便捷的问询与就诊绿色通道，并为患者量身打造系统化的健康管理方案，旨在实现对脂肪肝的有效防控，切实回应广大患者的健康需求，提供科学、全面的专业支持。 点击相应图片了解专利疗法 为积极响应国家政策，切实满足人民群众对肝脏健康的需求，四川华西肝病研究所特此免费开放线上问诊通道，为广大市民提供专业、系统的肝健康筛查与咨询服务。 有疑问请点击原文链接在线咨询，欢迎大家的评论区留言！ 声明：本内容仅为医学科普信息，不作为任何医疗指导。请在诊疗过程中务必遵循专业医生的建议和指导！本文部分内容及图片来自网络，如有侵权，请联系删除！ 关注以下平台了解更多资讯 点击关注 官方微博账号 点击了解 更多肝病特色治疗 点击查看 更多肝病科普视频 点“阅读原文”了解更多

iStock, Volodymyr Kryshtal After last year’s ‘stampede’ for FGF21 assets, the focus for the metabolic dysfunction-associated steatohepatitis space has shifted toward differentiated approaches, such as THR-β agonists and combination treatments, that seek to mirror the commercial success of Madrigal’s Rezdiffra. Before Madrigal’s Rezdiffra, the quest for a cure for metabolic dysfunction-associated steatohepatitis was a veritable graveyard for drug developers. However, the 2024 approval of that first drug for the inflammatory liver disease demonstrated to the pharma industry that the feat was possible. Not only that, but Madrigal proved it could be lucrative. In November 2025, the company announced in its third-quarter financial update that Rezdiffra had generated revenues of $287 million, just six quarters after its launch. Altogether, the product has amassed $817 million in revenue for its maker. This commercial success has not gone unnoticed, with three Big Pharma acquisitions in the MASH space in 2025, all worth billions of dollars. GSK began the rush in May by acquiring the investigational FGF21 analog efimosfermin alfa from Boston Pharmaceuticals for $1.2 billion upfront. Then, in September, Roche snapped up 89bio and another FGF21 analog pegozafermin for around $3.5 billion. Novo Nordisk followed weeks later with a $5.2 billion deal for Akero Therapeutics . The spate of acquisitions—all focused on FGF21 analogs—was centered on the success of Akero Therapeutics’ efruxifermin, which, in January 2025, showed positive long-term data in a mid-stage trial. “I think that really set off the stampede because there were very few FGF21 assets in development,” Edward Nash, managing director at Canaccord Genuity, told BioSpace . “This caused a big pharma reaction of, ‘Wait a minute, we need one of those too because we have a metabolic franchise and we need to be able to compete, especially given the data seen to date in the FGF21 space.’” This, alongside the approval of Novo Nordisk’s GLP-1 weight-loss blockbuster Wegovy for MASH, has led to the market opening up, and now, more companies want in, Nash said. All of this activity means the overall MASH landscape has changed significantly in the past year . With the key FGF21 developers off the market, there is an increased focus on the other assets in the field’s late-stage pipeline. Here are four candidates, each with differentiated mechanisms of action, that Big Pharma companies could have in their sights in 2026. Policy FDA Approves Madrigal’s Rezdiffra as First MASH Therapy Madrigal Pharmaceuticals’ Rezdiffra (resmetirom) is the first-ever approved therapy for metabolic dysfunction-associated steatohepatitis—a decision experts say could signal a sea change in treatment of the disease. March 14, 2024 · 6 min read · Jill Neimark Inventiva Homes In On Potential Next Oral MASH Drug Inventiva’s upcoming Phase III readout for pan-PPAR agonist lanifibranor is “the biggest event in the MASH space” this year, according to Nash. “It’s been a long trial, and it’s been long-awaited by the Street,” he said. “Depending on the data, [Inventiva] could definitely become another takeover candidate.” The French biotech is now solely focused on lanifibranor after halving its workforce and stopping all preclinical research not related to the drug to help fund its development in February 2025. This singular focus will help push the drug through its Phase III trial, with Inventiva poised to publish topline results from the NATiV3 trial in the second half of 2026. With these data expected, “lanifibranor could potentially be the next oral therapy approved for the treatment of patients with MASH,” CEO Frederic Cren said in a statement in April 2025. Lanifibranor is an oral small molecule that activates three peroxisome proliferator-activated receptor (PPAR) isoforms. Through the activation of these isoforms, Inventiva aims to address the key drivers of the disease, including inducing anti-fibrotic, anti-inflammatory and beneficial metabolic changes. In the NATIVE Phase IIb trial , reported in June 2020, lanifibranor achieved statistically significant MASH resolution and fibrosis improvement, with 42% of patients who received a 1200 mg dose seeing fibrosis improvement vs. 24% of placebo comparators after 24 weeks. The path to this year’s Phase III readout has not been straightforward for Inventiva. In February 2024 , the company voluntarily suspended screening and enrollment of patients in NATiV3 after a patient exhibited severely elevated aminotransferase levels. Now, Inventiva expects the results from NATiV3, if positive, to form the basis for a submission for regulatory approval. Viking Still Up For Grabs Viking Therapeutics has long attracted significant interest from Big Pharma. With pipeline assets that target both obesity and MASH, analysts have marked the biotech as one likely to draw suitors. For MASH, the company is developing VK2809, an oral thyroid hormone receptor-beta (THR-β) agonist. In the Phase IIb VOYAGE trial , VK2809 demonstrated a 37%-55% mean reduction in liver fat, with up to 75% of patients reaching MASH resolution without fibrosis worsening, according to data released in November 2024. In addition to these outcomes, the drug also demonstrated lipid-lowering effects and minimal side effects, Brian Lian, CEO of Viking, told BioSpace in an email. The overall body of evidence for VK2809 makes it “highly competitive” against both marketed products and drug candidates for MASH, he added. While Lian has previously stated that Viking would be open to partnering on the asset and confirmed that the company is still exploring partnering opportunities—he previously said that having a partner is not mandatory in order to bring the product to the market. Earnings MASH, Metsera Deals Send Analysts Marauding to Viking Viking Therapeutics CEO Brian Lian is watching the growth of interest in MASH and obesity but prepared to go it alone. October 23, 2025 · 6 min read · Annalee Armstrong Altimmune Open to Partnering Pemvidutide But Could Go It Alone Altimmune’s pemvidutide stands apart from others in the MASH pipeline due to its ability to preserve lean muscle mass, as well as ensuring MASH resolution and weight loss, a company spokesperson told BioSpace in an email. Pemvidutide is a weekly injectable GLP-1/glucagon dual receptor agonist that last month received the FDA’s Breakthrough Therapy Designation for MASH. This follows the November release of Phase IIb data from Altimmune’s IMPACT study, which showed that 52% of patients achieved MASH resolution without worsening of fibrosis, as well as improvements to liver fat content and weight loss. Altimmune is in a similar position to Viking, as both companies have the data to progress their drugs into Phase III, but may not begin those trials until they can find a partner, Nash said. “These two companies are all in on obesity, and that treatment area is already a big enough nut to crack,” he added. “To try to do that and run a MASH trial at the same time, I think you’re going to get a lot more bang for your buck if your molecule is differentiated in obesity.” The Altimmune spokesperson countered this, however, saying that independently bringing the asset forward in MASH is a “legitimate path forward.” However, they also noted that Altimmune remains open to any opportunity “that adds value, including partnerships.” Sagimet Looks to Combo FASN Inhibitor For Optimum Effect Like pemvidutide, Sagimet Biosciences’ denifanstat, an oral, once-daily fatty acid synthase (FASN) inhibitor that blocks the production of new fat in the liver, holds FDA Breakthrough Therapy Designation in MASH. Unlike Altimmune, however, Sagimet is not considering pursuing a Phase III trial alone, according to Nash. Instead, the California-based company is looking to cement its drug as a validated part of a combination therapy. In line with this, Sagimet released data in December from a Phase I trial that featured denifanstat paired with Rezdiffra, the current market leader. The trial showed that the combination was well-tolerated, and Sagimet plans to advance denifanstat into Phase II efficacy trials for MASH patients with F4 fibrosis. The combined treatment could boost fibrosis reduction more than Rezdiffra alone, Nash said. This type of combination approach is likely to be the future of MASH treatments because the disease is multifactorial, he added, with the main two targets being liver fat and fibrosis. So far, the marketed drugs— Rezdiffra and Wegovy—and the investigational pipeline have not proven outstanding at hitting both of these targets, making a combination treatment approach logical, Nash said. It seems the same could be true for the companies themselves, with partnering and M&A the likeliest outcome for the smaller players in the MASH landscape. “It’s hard to be successful as a standalone company,” Nash said. “There’s usually only one company when that happens, like Madrigal. I think we’re going to have one, maybe two biotechs, that can do it—after that, it’s going to be Big Pharma taking them in and developing them.”