Pegozafermin

▎药明康德内容团队编辑 Boston Pharmaceuticals今天宣布了一项2期试验的积极结果，该研究评估了每月一次的长效人类成纤维细胞生长因子21（FGF21）类似物efimosfermin alfa（BOS-580）对具有F2/F3期肝纤维化的代谢功能障碍相关脂肪性肝炎（MASH）患者的疗效与安全性。分析显示，BOS-580的治疗可显著改善肝纤维化≥1级，且MASH不会恶化，并且在24周内MASH缓解且肝纤维化不会恶化。详细数据将在美国肝病研究协会（AASLD）肝脏会议当中公布。根据此积极结果，该公司预计于2025年将临床项目推进到后期开发阶段。 MASH曾名为非酒精性脂肪性肝炎（NASH），是代谢功能障碍相关脂肪性肝病（MAFLD）的晚期形式。MASH是导致肝脏相关死亡的主要原因之一，对全球卫生系统造成日益加重的负担。此外，MASH患者，特别是那些具有更多代谢风险因素（高血压、合并2型糖尿病）的患者，心血管不良事件的风险增加，发病率和死亡率也相应提高。一旦MASH发展为显著的肝纤维化（F2和F3阶段），患者产生不良肝损伤结果的风险急剧上升。据统计，全球有超过2.5亿MASH患者，且预计到2030年，晚期患者数量将翻倍。研究显示，在超重或肥胖人群中，超过三分之一个体同时患有MASH。MASH患者在疾病早期通常症状不明显，甚至无明显症状，这常导致诊断延迟。与普通人群相比，MASH患者进展为晚期肝病（包括肝癌）的风险更高。 这次所公布的试验是一项随机、双盲、安慰剂对照的2期研究（N=84），旨在评估试验24周，在活检确诊的F2或F3纤维化MASH患者中，每月一次皮下注射300毫克BOS-580的疗效和安全性。 图片来源：123RF 关键疗效分析显示，45.2%的药物组患者在无MASH恶化的情况下获得≥1级的肝纤维化改善，而安慰剂组这一比例为20.6%（p=0.038）。有67.7%的药物组患者在无肝纤维化恶化的情况下实现MASH缓解，而安慰剂组这一比例为29.4%（p=0.002）。此外，38.7%的药物组患者实现MASH缓解并获得≥1级的肝纤维化改善，安慰剂组在此一数值上为17.6%（p=0.066）。 接受BOS-580治疗的患者在研究期间表现出纤维化生物标志物的快速显著改善，肝损伤和肝脏脂肪的非侵入性标志物显著减少。患有2型糖尿病受试者的糖化血红蛋白（HbA1c）水平也有显著且具临床意义的改善。在24周的治疗期间，接受BOS-580治疗的患者因不良事件而停药的比率低，患者发生胃肠道副作用和注射部位反应的总体发生率亦低。 ▲试验疗效结果摘要（图片来源：参考资料[1]） 目前BOS-580的2期临床开发计划正在继续进行，包括针对F2和F3患者的开放标签延长期研究，提供额外的24周治疗以评估长期安全性和疗效，并进一步验证BOS-580的低免疫原性。 BOS-580是一种每月一次皮下注射的长效人类FGF21变体，通过调节代谢通路来降低肝脂肪、改善肝损伤和炎症，并逆转MASH患者的肝纤维化。BOS-580在哺乳动物细胞中制造，具有类似人类的糖基化特性。目前该疗法正在开展针对MASH的2期临床试验。在早期的2a期12周临床研究中，BOS-580展现良好的安全性特征，并显示出在统计学上显著降低患者的肝脂肪含量、肝损伤标志物和纤维化标志物，同时改善患者的代谢生物标志物。 ▲在之前公布的2a期试验中，MASH患者在接受BOS-580治疗12周后在晚期脂肪肝纤维化代谢组学复合生物标志物上获得改善（图片来源：参考资料[2]） MASH疗法的开发是近年来产业关注的领域。今年3月，美国FDA加速批准Madrigal Pharmaceuticals药品Rezdiffra（resmetirom）联合饮食和运动，治疗患有中重度肝纤维化的MASH成人患者。根据新闻稿，这是获得FDA批准的首款MASH疗法，标志着该领域的一项重要里程碑。 这个月初，诺和诺德（Novo Nordisk）宣布其减重疗法Wegovy（semaglutide，司美格鲁肽）在ESSENCE关键临床3期试验中，与安慰剂相比，可显著缓解MASH患者的肝纤维化并实现脂肪性肝炎消退。诺和诺德预计将于2025年上半年向美国和欧盟监管单位递交Wegovy用于治疗MASH的监管申请。Sagimet Biosciences则在今年10月宣布，其在研口服FASN小分子抑制剂denifanstat用于治疗MASH的临床2b期试验FASCINATE-2的结果发表于《柳叶刀》子刊The Lancet Gastroenterology & Hepatology。结果显示，denifanstat在疾病活动、MASH缓解和肝纤维化方面均实现了具有统计学显著性和临床意义的改善，支持这一疗法进入3期临床试验。 同样专注于MASH的还有89bio公司。去年9月，其所开发的FGF21类似物pegozafermin用于治疗MASH的2b期试验结果登上《新英格兰医学杂志》，分析显示，有37%的15 mg pegozafermin治疗组患者的MASH得到缓解，此数值在安慰剂组仅有2%，该疗法用于治疗MASH的3期试验已经启动。而Akero Therapeutics的在研药品efruxifermin（EFX）用于治疗MASH的3期试验也已经开展。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Boston Pharmaceuticals to Announce Positive Phase 2 Data on Efimosfermin Alfa (BOS-580) in F2/F3 MASH During Late-Breaking Oral Presentation at AASLD 2024, The Liver Meeting®. Retrieved November 15, 2024 from https://www.businesswire.com/news/home/20241115839453/en/Boston-Pharmaceuticals-to-Announce-Positive-Phase-2-Data-on-Efimosfermin-Alfa-BOS-580-in-F2F3-MASH-During-Late-Breaking-Oral-Presentation-at-AASLD-2024-The-Liver-Meeting%C2%AE [2] BOS-580, a long-acting FGF21 analogue, treatment shows beneficial changes in the circulating lipidome and improves MASEF score in patients with phenotypic metabolic dysfunction-associated steatohepatitis in a Phase 2a randomized, placebo-controlled, 12-week study. Retrieved November 15, 2024 from https://static1.squarespace.com/static/639a279aa2f7e15993210ea2/t/66e1d2827634e51ef9149505/1726075523483/WED-220+BOS-580+Part+A+Lipidomics+EASL+2024+Poster+5.9.24+Final.pdf 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

New post-hoc analyses reinforce pegozafermin’s potential anti-fibrotic effects and the potential utility of non-invasive tests which correlate to histological endpoints SAN FRANCISCO, Nov. 15, 2024 (GLOBE NEWSWIRE) -- 89bio, Inc. (Nasdaq: ETNB), a clinical-stage biopharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and cardiometabolic diseases, announced new analyses of data from the Phase 2b ENLIVEN trial evaluating pegozafermin in metabolic dysfunction-associated steatohepatitis (MASH) patients with advanced fibrosis. The findings were presented in four poster sessions at The American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® being held in San Diego, California. "We are excited to present additional analyses from our Phase 2b ENLIVEN trial at this year’s Liver Meeting, which reinforce pegozafermin's potential effectiveness in reversing fibrosis and preventing progression to cirrhosis in patients with advanced MASH," said Hank Mansbach, Chief Medical Officer of 89bio. "These analyses strengthen our confidence in the design of our Phase 3 trials for both cirrhotic and non-cirrhotic MASH, and we look forward to building on this momentum as we advance these trials."“MASH is often underdiagnosed and undertreated, which can lead to cirrhosis and severe complications like the need for liver transplantation,” said Naim Alkhouri, MD, Chief Medical Officer, Chief of Transplant Hepatology, and Director of the Fatty Liver Program at Arizona Liver Health (ALH). “These post-hoc analyses demonstrate the potential of NITs like FAST and AGILE3+ to identify high-risk patients more conveniently, potentially reducing the need for liver biopsy. The results show that pegozafermin not only improved patients’ FAST scores but also achieved both MASH resolution and fibrosis improvement, indicating its potential as a treatment option for patients with advanced MASH.” Publications Presented at the Meeting: Pegozafermin reduced progression to cirrhosis: A post-hoc analysis from the Phase 2b ENLIVEN study (Publication 1563).Biomarker response in metabolic dysfunction-associated steatohepatitis (MASH) patients with high-risk baseline FAST scores: Observations from the ENLIVEN Phase 2b trial with pegozafermin (Publication 1549).Diagnostic potential of FAST and AGILE3+ scores for F2/F3 fibrosis: An analysis of the Phase 2 ENLIVEN study (Publication 2014).Analysis and integration of machine learning for biomarker assessments and their association with treatment response: Insights from the ENLIVEN Phase 2b trial of pegozafermin (Publication 2008) A copy of the AASLD posters will be accessible under “Scientific Publications” in the pipeline section of 89bio's website. About ENLIVENENLIVEN was a multicenter, randomized, double-blind, placebo-controlled Phase 2b trial designed to evaluate the safety and efficacy of weekly or every-two-week dosing of pegozafermin for the treatment of patients with biopsy confirmed MASH and NAS ≥ 4 for 48 weeks. In the trial, 192 patients were dosed with pegozafermin 15mg QW, 30mg QW and 44mg Q2W, or placebo. Primary outcomes measured were proportion of participants with resolution of MASH without worsening of fibrosis and proportion of participants with ≥1 stage decrease in fibrosis stage with no worsening of MASH at week 24. Secondary measures included change from baseline in liver fat, liver enzymes, noninvasive markers of liver fibrosis, glycemic control, lipoproteins, and body weight as well as safety and tolerability measures. Patients who entered the blinded extension phase were subsequently treated for an additional 24 weeks for a total treatment period of 48 weeks. Some patients who were on placebo (n=19) were re-randomized to receive pegozafermin in the extension phase. Key endpoints in the extension phase include liver fat and noninvasive markers of liver fibrosis and inflammation. ENLIVEN achieved high statistical significance on primary histology endpoints with 30mg QW and 44mg Q2W dosing at week 24 and the results were published in the New England Journal of Medicine. To learn more about the clinical trial, visit clinicaltrials.gov: NCT04929483. About pegozaferminPegozafermin is a specifically engineered glycoPEGylated analog of fibroblast growth factor 21 (FGF21) being developed for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) and severe hypertriglyceridemia (SHTG). FGF21 is an endogenous hormone that has broad effects such as regulating energy expenditure, glucose and lipid metabolism. In clinical trials, pegozafermin has demonstrated direct anti-fibrotic and anti-inflammatory effects on the liver, as well as reduced triglyceride levels, improved insulin resistance and glycemic control, and continued to demonstrate a favorable safety and tolerability profile. Pegozafermin received Breakthrough Therapy designation (BTD) status from the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) status from the European Medicines Agency (EMA) for the treatment of MASH with fibrosis. Pegozafermin is being studied in the Phase 3 ENLIGHTEN trial program for MASH and the Phase 3 ENTRUST trial for SHTG. About 89bio89bio is a clinical-stage biopharmaceutical company dedicated to the development of best-in-class therapies for patients with liver and cardiometabolic diseases who lack optimal treatment options. The company is focused on rapidly advancing its lead candidate, pegozafermin, through clinical development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) and severe hypertriglyceridemia (SHTG). Pegozafermin is a specifically engineered, potentially best-in-class fibroblast growth factor 21 (FGF21) analog with unique glycoPEGylated technology that optimizes biological activity through an extended half-life. The company is headquartered in San Francisco. For more information, visit www.89bio.com or follow the company on LinkedIn. Forward-Looking Statements Certain statements in this press release may constitute "forward-looking statements" within the meaning of the federal securities laws, including, but not limited to, statements regarding the therapeutic potential and utility, efficacy and clinical benefits of pegozafermin, the safety and tolerability profile of pegozafermin and trial designs, clinical development plans and timing for pegozafermin, including confirming the long-term efficacy, tolerability and sustained improvement in key liver health markers observed in the Phase 2b ENLIVEN trial evaluating pegozafermin in the current Phase 3 trials for both cirrhotic and non-cirrhotic MASH. Words such as "may," "might," "will," "objective," "intend," "should," "could," "can," "would," "expect," "believe," "design," "estimate," "predict," "potential," "anticipate," "goal," "opportunity," "develop," "plan" or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While 89bio believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in 89bio's filings with the Securities and Exchange Commission (SEC)), many of which are beyond 89bio's control and subject to change. Actual results could be materially different. Risks and uncertainties include: expectations regarding the design of the ENLIGHTEN-Fibrosis and ENLIGHTEN-Cirrhosis trials; expectations regarding the timing and outcome of the ENTRUST Phase 3 trial in SHTG; 89bio's ability to execute on its strategy; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; receipt of BTD for pegozafermin in MASH may not result in a faster development process, review or approval compared to drugs considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA; 89bio's substantial dependence on the success of its lead product candidate; competition from competing products; the impact of general economic, health, industrial or political conditions in the United States or internationally; the sufficiency of 89bio's capital resources and its ability to raise additional capital; and other risks and uncertainties identified in 89bio’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 and other subsequent disclosure documents filed with the SEC. 89bio claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. 89bio expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. Investor Contacts:Annie Chang89bio, Inc.investors@89bio.com PJ KelleherLifeSci Advisors, LLC+1-617-430-7579pkelleher@lifesciadvisors.com Media Contact:Sheryl SeapyReal Chemistrysseapy@realchemistry.com