Glucagon

GSK 和波士顿制药（Boston Pharmaceuticals）5月14日宣布双方已达成协议，葛兰素史克将收购波士顿制药公司的子公司BP Asset IX，以获得Efimosfermin的销售权。Efimosfermin是一种III期临床准备就绪的、在研专科药物，用于治疗脂肪性肝病（SLD）。根据协议，葛兰素史克公司将支付12亿美元的预付款，并有可能支付总额达8亿美元的额外里程碑付款。Efimosfermin 是诺华自研的一种新型、每月一次给药的成纤维细胞生长因子 21 (FGF21) 类似物。原文链接：https://www.businesswire.com/news/home/20250513598541/en/GSK-to-acquire-efimosfermin-a-phase-III-ready-potential-best-in-class-specialty-medicine-to-treat-and-prevent-progression-of-steatotic-liver-disease-SLD原文正文Boston Pharmaceuticals, a leading clinical stage biopharmaceutical company developing highly targeted therapies for patients with serious liver diseases, today announced that they have entered into an agreement under which GSK will acquire Boston Pharmaceuticals’ lead asset, efimosfermin alfa. Efimosfermin is a phase III-ready, potential best-in-class, investigational specialty medicine to treat and prevent progression of steatotic liver disease (SLD). Under the agreement, GSK will pay $1.2 billion upfront, with potential for additional success-based milestone payments totalling $800 million.Efimosfermin is a novel, once-monthly fibroblast growth factor 21 (FGF21) analog therapeutic in clinical development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), including cirrhosis, and future development in alcohol-related liver disease (ALD), both forms of SLD. Given efimosfermin’s direct antifibrotic mechanism of action and GSK’s data-driven insights from work in human genetics and disease phenotyping, it has potential to address more advanced stages of SLD and opportunity in combination with GSK’990, a siRNA therapeutic in development for other subsets of patients with SLD.The acquisition of efimosfermin is highly aligned to GSK’s R&D focus on science related to the immune system and is further evidence of the company’s intent to build on its deep understanding of fibrosis and auto-inflammation to develop precision interventions that stop and reverse disease progression.SLD represents an area of significant unmet medical need affecting approximately 5% of the global population with limited therapeutic options for patients.1 SLD, including MASH and ALD, is characterised by the accumulation of fat in the liver (steatosis), with associated inflammation and fibrosis. ALD affects about 26 million patients globally, and together with MASH, is the leading cause of liver transplant in the US, representing a significant burden and cost on healthcare utilisation.1,3 Substantial and disproportionate costs are associated with end-stage liver disease. Interventions that reduce moderate-to-advanced fibrosis to prevent progression of cirrhosis, liver cancer, hospitalisations and transplant could save the US healthcare system between $40 - 100 billion over the next two decades.4Recent data from a phase II trial of efimosfermin, designed to assess the efficacy and safety of a monthly subcutaneous dose in participants with biopsy-confirmed moderate-to-advanced (F2 or F3) MASH, showed that efimosfermin rapidly and significantly reversed liver fibrosis and stopped its progression, with a manageable tolerability profile. These data suggest potentially greater fibrosis improvement compared to that seen with other therapeutic approaches and with benefit expected independent of background glucagon-like peptide-1 (GLP-1) therapy. In addition, efimosfermin could offer triglyceride reduction and improved glycaemic control, important considerations for MASH patients who frequently face cardiometabolic co-morbidities. Efimosfermin’s unique properties, including low immunogenicity and an extended half-life, also offer the potential for a monthly dosing regimen and improved patient convenience. Full data from the trial was presented at the American Association for the Study of Liver Diseases (AASLD) Meeting in November 2024.5Tony Wood, Chief Scientific Officer, GSK said: “The FGF21 class has shown some of the most exciting data in MASH including first-in-disease evidence of cirrhosis reversal, and efimosfermin has the potential to define a new standard-of-care with its monthly dosing and tolerability profile. Efimosfermin will significantly expand our hepatology pipeline and provide us the opportunity to develop a new potential best-in-class medicine with first launch expected in 2029. It complements GSK‘990, also in development for ALD and MASH, offering GSK options to develop both monotherapy and potential combinations to improve patient outcomes.”Elias Zerhouni MD, Chair of the Board, Boston Pharmaceuticals, said: “I am very proud of today’s agreement with GSK, a company I know and admire, and of the outstanding work of the Boston Pharmaceuticals team led by Sophie Kornowski. Notably, this would not have been possible without the impressive, sustained and long-term strategic commitment to leading edge science and biotechnology ventures of the Bertarelli family, which led to the development of our Efimosfermin alfa as a potential best-in-class therapy in its therapeutic field. We are delighted that GSK, a global leader, recognized Efimosfermin’s potential to address a growing global public health concern and unmet medical need. Together, we look forward to Efimosfermin alfa’s ongoing journey to become a best-in-class treatment for patients with SLD.”Sophie Kornowski Pharm D, Chief Executive Officer, Boston Pharmaceuticals said: “Today marks a pivotal moment for Boston Pharmaceuticals and Efimosfermin alfa, as we begin a new chapter with GSK, a global organization with proven expertise in liver disease, and a shared commitment to patients. Our accomplishments were made possible thanks to the dedicated Boston Pharmaceuticals team, who focused on our mission to develop Efimosfermin with a great sense of urgency. I am especially grateful to Ernesto Bertarelli for his unflinching support and the commitment of his expertise over the last few years."The addition of efimosfermin further strengthens GSK’s hepatology pipeline of specialty medicines aimed at addressing both viral (chronic hepatitis B) and steatotic (SLD) drivers of fibrotic liver diseases.Financial considerationsUnder the terms of the agreement, GSK will acquire BP Asset IX, Inc., a subsidiary of Boston Pharmaceuticals, to access efimosfermin. GSK will pay up to $2 billion of total cash consideration, comprising an upfront payment of $1.2 billion and up to $800 million in success-based milestone payments. GSK will also be responsible for success-based milestone payments as well as tiered royalties for efimosfermin owed to Novartis Pharma AG.GSK will account for the transaction as a business combination. This transaction is subject to customary conditions, including applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the US.For GSK, Evercore Partners International LLP is acting as exclusive financial advisor and Cleary Gottlieb Steen & Hamilton LLP as legal counsel.For Boston Pharmaceuticals, Centerview Partners LLC is acting as exclusive financial advisor and Sullivan & Cromwell LLP as legal counsel.About efimosfermin alfaEfimosfermin is an investigational, once-monthly subcutaneous injection of a long-acting variant of FGF21 that is designed to regulate key metabolic pathways to decrease liver fat, ameliorate liver inflammation, and reverse liver fibrosis in patients with MASH. Efimosfermin is currently in trials for moderate to advanced fibrosis, including cirrhosis and is not available for prescription anywhere in the world.About Boston PharmaceuticalsBoston Pharmaceuticals is a clinical-stage biopharmaceutical company that leverages an experienced and committed drug development team to advance a portfolio of highly differentiated therapies that may address important unmet medical needs in serious liver diseases. Boston Pharmaceuticals is a portfolio company of B-Flexion, a private, entrepreneurial investment firm which manages the combined funds and investments associated with the Bertarelli family and also partners with sophisticated capital to meet the shared goal of delivering exceptional value over the generations, while also contributing positively to society.About GSKGSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.References1 Global Burden of Disease Study 2017 Cirrhosis collaborators. 20202 Allen et al. Postgraduate Medicine. 2024, Vol 136, No. 3, 229–245.3 Younossi et al. Hepatol Commun. 2023 Dec 22;8(1):e03524 Wallace, Carolyn et al. Journal of Hepatology, Volume 0, Issue 05 Hepatology (2004) Late-Breaking Abstract Supplement p28-30 TLM2024LBA_20241115A.pdf

近日，华东医药股份有限公司（以下简称“公司”）控股子公司浙江道尔生物科技有限公司（以下简称“道尔生物”）自主研发的全球首创（First-in-class）的靶向成纤维细胞生长因子21受体（Fibroblast growth factor 21 receptor，FGF21R）、胰高血糖素受体（Glucagon receptor，GCGR）和胰高血糖素样肽-1受体（Glucagon-like peptide-1 receptor，GLP-1R）的长效三重激动剂DR10624在新西兰治疗肥胖合并高甘油三脂血症的Ib/IIa期临床研究结果在荷兰阿姆斯特丹举办的2025年欧洲肝病研究学会年会（EASL Congress 2025）上首次发布。研究结果“DR10624, a First-In-Class, FGF21 Receptor (FGF21R)/Glucagon Receptor (GCGR)/GLP-1 Receptor (GLP-1R) Triple Agonist Rapidly and Significantly Reduced Liver Fat in Obese Subjects With Modest Hypertriglyceridemia: A 12-Week Randomized, Placebo-Controlled, Double-Blind, Multi-Center Trial”入选了大会的最新突破（Late-Breaker），展示了DR10624在肥胖合并高甘油三酯血症受试者中取得的关键研究数据。DR10624 Ib/Ⅱa期临床试验情况DR10624的Ib/Ⅱa临床试验是在新西兰开展的一项随机、双盲、安慰剂对照、多次给药剂量递增的研究。主要纳入标准为：（1）年龄为18至70岁（含界值），男性或女性；（2）筛选期BMI在30-45kg/m2范围内（含界值）；（3）筛选时空腹甘油三酯≥150 mg/dL （1.7 mmol/L），且＜500 mg/dL （5.7 mmol/L）。每个队列筛选合格的受试者按照5：1的比例接受DR10624或等体积安慰剂的皮下注射给药，给药频率为每周一次，连续给药12周。主要有效性终点为肝脏脂肪含量（Liver Fat Content，LFC）较基线变化、空腹甘油三脂（TG）较基线变化等。研究共纳入49例受试者，DR10624组41例，安慰剂组8例。所有受试者接受DR10624的各剂量组与安慰剂组间年龄、性别、体重、BMI和空腹甘油三酯水平相对均衡。DR10624在受试者中展现出优异的降低肝脏脂肪的药效。治疗12周后，DR10624的各剂量组（12.5 mg、25 mg、50 mg和75 mg剂量滴定组）的肝脏脂肪含量较基线相对降幅分别为51.9%、77.8%、79.0%和75.8%，显著高于安慰剂组的26.3%。图： 与基线相比，第85天肝脏脂肪相对变化（%）在基线肝脏脂肪含量≥8%的受试者中，DR10624的各剂量组（12.5 mg、25 mg、50 mg和75 mg剂量滴定组）的LFC较基线相对降幅分别为58.3%、83%、89.2%、和87.2%，显著高于安慰剂组的27.2%。表：基线＞8%的受试者在接受12周治疗后LFC的变化（通过MRI-PDFF评估）对于肝脏脂肪含量相对降低50%这一指标（LFC相对降低50%在临床一般认为可以大概率取得脂肪肝炎的组织学缓解，即MASH resolution），DR10624的各剂量组（12.5 mg、25 mg、50 mg和75 mg剂量滴定组）中实现LFC相对降低≥50%的受试者比例分别为66.7%、88.9%、100%和85.7%。在基线肝脏脂肪含量≥8%的受试者中，DR10624所有治疗组（n=19）有94.7%在第12周实现LFC相对降低≥50%，而安慰剂组（n=6）这一比例为16.7%。DR10624在受试者中还展现出显著的降低血脂的药效。与安慰剂相比，所有DR10624治疗组的空腹甘油三酯（TG）较基线降幅均具有统计学显著性。第12周时，DR10624各剂量组（12.5 mg、25 mg、50 mg和75 mg剂量滴定组）的甘油三酯较基线相对降幅分别为31.32%、58.89%、70.16%和55.19%，而安慰剂组仅为6.94%。在50 mg和75 mg剂量滴定组中，与安慰剂相比，受试者的极低密度脂蛋白胆固醇（VLDL-C）、总胆固醇（TC）、非高密度脂蛋白胆固醇（non-HDL-C）均呈现统计学显著降低。DR10624在受试者中还展现出较好的降低胰岛素抵抗的药效。临床试验中使用胰岛素抵抗指数（HOMA-IR）来检测受试者胰岛素敏感性的变化。在第12周时，DR10624的50 mg和75 mg剂量滴定组的受试者的HOMA-IR较基线相对变化分别为-42.7%和-35.9%，而安慰剂组为+5.77%。安全性方面，DR10624在本研究中耐受性良好，未发生与研究药物相关的严重不良事件，且导致治疗终止的治疗相关不良事件发生率较低。上述Ib/IIa期临床研究数据显示，DR10624在临床每周给药一次、连续给药12周后，可实现具有临床意义的肝脏脂肪含量降低的药效，并在血脂谱改善和胰岛素敏感性提升方面展现出具有统计学意义的显著改善的疗效，使得受试者获得综合性的代谢获益。在新西兰完成的这项Ib/IIa期临床研究结果进一步验证了DR10624治疗重度高甘油三脂血症（SHTG），代谢功能障碍相关脂肪性肝病/代谢相关脂肪性肝炎（MASLD/MASH）等疾病的潜力。DR10624研发及注册情况DR10624为道尔生物自主研发的一款长效三靶点激动剂，其为靶向FGFR1c/Klothoβ（FGF21R）、GLP-1受体（GLP-1R）和GCG受体（GCGR）的候选创新蛋白药物。DR10624由N端靶向GLP-1R/GCGR的嵌合肽段与工程化改造的IgG1 Fc融合，并在Fc的C末端融合重组的FGF21突变体。DR10624注射液目前正在中国开展治疗合并肝纤维化高风险的代谢相关脂肪性肝病以及代谢合并酒精相关脂肪变性肝病II期临床研究，并于2025年4月完成首例受试者入组。与此同时，此前在中国已启动的另一项DR10624治疗重度高甘油三酯血症的II期临床研究已完成全部患者入组，预计2025年第三季度获得揭盲后的顶线结果。此外，DR10624用于2 型糖尿病和体重适应症的中国临床试验申请也先后获批。声明1、本新闻旨在分享公司（或合作伙伴）研发工作的前沿进展资讯，非广告用途，相关信息并非针对患者，仅供医疗卫生专业人士参考使用；2、本新闻稿中内容不涉及对任何药品和/或适应症作推荐；3、本新闻稿中涉及的信息仅供参考，具体信息以公司在深圳证券交易所发布的文件为准。公司新闻稿和公告不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。若您想了解具体疾病诊疗信息，请遵从医生或其他医疗卫生专业人士的意见或指导；4、本新闻稿中涉及的产品包装仅供参考，具体请以实际为准；5、截至本文发布，DR10624注射液尚未被国家药品监督管理局批准上市；6、本新闻稿中可能会包含某些前瞻性表述。这些表述本质上具有相当风险和不确定性。在使用“预期”、“相信”、“预测”、“期望”、“打算”及其他类似词语进行表述时，凡与本公司有关的，均属于前瞻性表述。本公司并无义务不断地更新这些预测性陈述。这些前瞻性表述是基于本公司管理层在做出表述时对未来事务的现有看法、假设、期望、估计、预测和理解。这些表述并非对未来发展的保证，会受到风险、不确性及其他因素的影响，有些是超出本公司的控制范围，难以预计。因此，受我们的业务、竞争环境、政治、经济、法律和社会情况的未来变化及发展的影响，实际结果可能会与前瞻性表述所含资料有较大差别。本公司、本公司董事及雇员代理概不承担 (a) 更正或更新本网站所载前瞻性表述的任何义务;及 (b) 若因任何前瞻性表述不能实现或变成不正确而引致的任何责任。