Icosabutate

▎药明康德内容团队编辑 NorthSea Therapeutics公司日前宣布，在研疗法icosabutate用于治疗经活检确认的代谢相关性脂肪性肝炎（MASH）患者的2b期临床试验ICONA的结果已发表于Journal of Hepatology。Icosabutate在纤维化改善方面显示出极为鼓舞人心的结果，该结果由人工智能（AI）辅助数字病理学工具（DP/AI）以及传统组织学评估均予以确认。 试验主要发现包括： 经人工智能辅助数字病理学评估，在600 mg治疗组中，49.2%患者实现了肝纤维化改善≥1级，安慰剂组这一数值为25.7%（p=0.02）。在纤维化级别为F3–F4的患者中，icosabutate治疗组中32.7%患者在MASH未恶化的情况下实现了纤维化改善≥1级，安慰剂组这一数值为9.6%（p=0.004）。 传统组织学分析显示，在F2–F3患者中，icosabutate的300 mg和600 mg治疗组分别有30.8%和28.3%患者实现了纤维化改善≥1级，安慰剂组这一数值为13%（p=0.065）。在2型糖尿病患者中，icosabutate的300 mg和600 mg治疗组分别有28.6%和21.2%患者实现了纤维化改善≥1级，安慰剂组这一数值为0%（p=0.003）。 Icosabutate总体安全性良好，耐受性佳，治疗中出现的副作用均为轻度至中度，且未报告药物性肝损伤。 Icosabutate是一种是一种口服、肝脏靶向、半合成的二十碳五烯酸衍生物。新闻稿表示，该药物可与针对体重和肝脏脂肪水平的GLP-1类药物构成组合疗法。临床前研究已显示GLP-1类药物与icosabutate在减轻肝纤维化方面具有协同作用。 ▲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] NorthSea Therapeutics Announces Publication of Positive Results from Phase 2b ICONA Clinical Trial of Icosabutate in Biopsy-Confirmed F1-F3 MASH in Journal of Hepatology. Retrieved March 7, 2025, from https://northseatherapeutics.com/en/news/northsea_therapeutics_announces_publication_of_positive_results_from_phase_2b_icona_clinical_trial_of_icosabutate_in_biopsy_conf/ 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

Phase 2a study evaluating the safety, tolerability, PK, and PD of Orziloben in IFALD The study will enroll up to 36 adult subjects at multiple sites in North America Study strengthens NST’s position as a multi-asset, clinical stage company AMSTERDAM--(BUSINESS WIRE)-- NorthSea Therapeutics B.V. (‘NST’, or the ‘Company’), a biotech company developing novel and innovative strategies for the treatment of non-alcoholic steatohepatitis (NASH) and other liver-associated metabolic diseases, today announced the dosing of the first patient in its Phase 2a clinical trial of Orziloben (NST-6179) in intestinal failure-associated liver disease (IFALD), an orphan liver disease affecting individuals on prolonged intravenous (parenteral) nutrition (PN). The trial is a randomized, double-blind, Phase 2a, placebo-controlled study, which will be conducted at multiple sites across North America. It is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of Orziloben in adult subjects with IFALD. The readout of the trial is anticipated in H2 2025. For more information on the study, see ClinicalTrials.gov (NCT05919680). Commenting on the milestone, Rob de Ree, NST’s CEO, said: "Dosing the first patient in our Phase 2a trial for Orziloben in IFALD is a significant achievement for NorthSea Therapeutics, and is a testament to our commitment to advance innovative treatments for liver diseases. There is a critical need for effective therapies in IFALD as, to date, there are no drug therapies approved to treat this orphan indication. We believe Orziloben has the potential to make a substantial impact in addressing this unmet medical need." IFALD is a complex condition, characterized by the development of hepatic inflammation, cholestasis and steatosis, in patients with intestinal failure and/or short bowel syndrome. It is known to be associated with prolonged administration of PN. One major concern for patients with the condition is the development of hepatic fibrosis, which can progress to cirrhosis and liver failure. Preclinical studies have demonstrated the efficacy of Orziloben in preventing severe cholestasis, fibrosis, and other key markers of liver damage in models where PN was administered. In one pre-clinical model of PN-induced liver injury, Orziloben treatment completely prevented severe cholestasis and the development of fibrosis. Orziloben was also shown to prevent the pronounced increase in markers of liver damage in another in vivo model of PN in combination with an inflammatory stimulus (endotoxin). Furthermore, Orziloben significantly reduced the number of myofibroblasts, the main collagen producing cell in the liver, in addition to hepatic inflammation and steatosis in a model of established fibrosis. The unique ability of Orziloben to target multiple pathogenic components of IFALD, and its potential for oral dosing, make it a promising candidate for the treatment of PN-induced liver disease, as well as other liver disease indications. Professor Palle Bekker Jeppesen, Head of the Department of Intestinal Failure and Liver Diseases at Rigshospitalet in Copenhagen, added: “Orziloben has shown consistently robust efficacy in several pre-clinical models, and has demonstrated a strong preventative effect on important disease pathophysiology components, such as cholestasis and fibrosis. If these impressive pre-clinical effects translate to clinical effects, Orziloben has the potential to become an effective therapeutic for intestinal failure patients who currently have limited treatment options.” If you are interested in learning more about Orziloben, the NorthSea Therapeutics team will be attending the ASPEN 2024 Nutrition Science & Practice Conference (2-5 March, Tampa, Florida). Please contact: carine.beysen@northseatherapeutics.com Notes to Editors About Intestinal failure-associated liver disease (IFALD) IFALD is a multifactorial condition in patients with intestinal failure and/or significant resection. It is characterized by the development of hepatic inflammation, cholestasis, and steatosis. It has been shown to be associated with prolonged administration of parenteral nutrition (PN). Patients with IFALD are often asymptomatic in the early stages but progress with signs of liver damage such as increases in liver chemistry tests, steatosis, and fibrosis. If left untreated, the liver damage can eventually lead to liver failure, transplant, and death. There is a clear medical need for treatment options for patients and there is currently no approved therapy for IFALD. About Orziloben Orziloben is a novel, orally administered, highly potent, synthetic, medium chain fatty acid analogue (MCFA). MCFAs are rapidly absorbed via passive diffusion, rather than receptor-mediated transport, but are rapidly metabolised. Orziloben was designed to maintain the ease of transport to the liver and into cells that is characteristic of unmodified MCFAs, whilst offering enhanced pharmacological effects by avoiding rapid metabolism. In one pre-clinical model of intravenous PN-induced liver injury, Orziloben treatment completely prevented severe cholestasis and the development of fibrosis. Orziloben was also shown to prevent the pronounced increase in markers of liver damage in a model of PN in combination with an inflammatory stimulus (endotoxin). Furthermore, Orziloben significantly reduced the number of myofibroblasts, the main collagen producing cell in the liver, in addition to hepatic inflammation and steatosis in a model of established fibrosis. The ability of Orziloben to target multiple pathogenic components of IFALD, in addition to its potential for oral dosing, highlight its potential to become a highly efficacious drug for the treatment of PN-induced liver disease as well as potentially other liver disease indications. About NorthSea Therapeutics NorthSea Therapeutics B.V. (NST) is a Dutch biotech company focused on developing structurally engineered fatty acids (‘SEFAs’) for the treatment of NASH and other metabolic disorders. NST licensed the rights to its lead compound icosabutate and a library of SEFAs from BASF Norge AS (formerly known as Pronova BioPharma Norge AS), who developed Lovaza® (US brand, branded Omacor® in Europe), a blockbuster cardiometabolic drug. Icosabutate has been found safe and well tolerated in two prior Phase 2 clinical studies for treatment of hypertriglyceridemia and mixed dyslipidemia and is currently in clinical development for NASH. The results of the icosabutate Phase 2b ICONA NASH trial were announced in November 2023. Two additional SEFAs are also in clinical development: NST-1024, which is being developed for SHTG, has entered Phase 2a; and Orziloben, which is being developed for the orphan indication IFALD (Intestinal Failure Associated Liver Disease), initiated a Phase 2a study in Q1-2024. NST is headquartered in the Netherlands with a presence in Norway and the US and is supported by Forbion Growth, Forbion Ventures, Novo Holdings, venBio Partners and Sofinnova investments, Ysios Capital, BGV and NSV. Find out more about us online at: