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

AMSTERDAM--(BUSINESS WIRE)--NorthSea Therapeutics B.V. (‘NST’, or the ‘Company’), a private, late-stage clinical biotechnology company developing novel strategies to treat metabolic, cholestatic, and fibrotic diseases, today announced that results from the Phase 2b ICONA clinical trial of icosabutate in biopsy-confirmed F1-F3 metabolic dysfunction-associated steatohepatitis (MASH) were published in the Journal of Hepatology. The publication, “A phase IIb randomised-controlled trial of the FFAR1/FFAR4 agonist icosabutate in MASH” reported that treatment with icosabutate demonstrated highly encouraging results in the most clinically meaningful endpoint, fibrosis improvement, as assessed by both artificial intelligence (AI)-assisted digital pathology tools (DP/AI) tools and conventional histological assessment. “The data presented in this publication, both conventional and AI-assisted histology, suggest improvements in fibrosis in patients treated with icosabutate,” said Arun Sanyal, M.D., Director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health and the last author of the Journal of Hepatology paper. “The unique mechanism of action, unrelated to a decrease in liver fat, will provide patients with metabolic dysfunction-associated steatotic liver disease, or MASLD, with more options for therapy in the future.” The results are consistent with icosabutate’s anti-fibrotic effects in pre-clinical models and anti-proliferative effects in isolated stellate cells1,2. Key findings include: AI-assisted digital pathology 49.2% (p=0.02 vs placebo) of 600 mg treated patients achieving a ≥1-stage improvement in fibrosis versus 25.7% of placebo treated patients as assessed by qFibrosis (Histoindex). 32.7% (p=0.004 vs placebo) of F3-F4 patients treated with 600 mg icosabutate achieved ≥1-stage improvement in fibrosis without worsening of MASH versus 9.6% of placebo treated patients as assessed by AIM-MASH (Path-AI). Conventional histological analysis 30.8% (p=0.036 vs placebo) and 28.3% (p=0.065 vs placebo) of F2-F3 patients treated with icosabutate 300 and 600 mg respectively achieving a ≥1-stage improvement in fibrosis versus 13% of placebo treated patients. 28.6% (p=0.003 vs placebo) and 21.2% (p=0.013 vs placebo) of Type 2 diabetic patients treated with icosabutate 300 and 600 mg respectively achieving a ≥1-stage improvement in fibrosis versus 0% of placebo treated patients. The clinical relevance of the AIM-MASH findings is highlighted by recently published data demonstrating that continual scores in AIM-MASH determined F3-F4 MASH patients strongly predicted progression free survival3. A 3-panel read method was used for the conventional histological analysis. To provide a more relevant cross-study comparison, we also performed an exploratory analysis of fibrosis improvement using the same pathologist used in the current study and in multiple single reader F2-F3 phase 2 MASH studies. A ≥1-stage improvement in fibrosis was seen in 17.5%, 29.2% and 40.9% of patients (F2-F3) in the placebo, 300 mg and 600 mg arms respectively. The publication also highlights the broad therapeutic effect of 600 mg icosabutate on multiple biomarkers of liver health, systemic inflammation and glycemic control, including but not limited to: Significant reductions in fasting plasma glucose, insulin and HOMA-IR in conjunction with a ~1% placebo adjusted decrease in HbA1c in type 2 diabetic patients with poor glycemic control at baseline. Significant improvements in ALT, AST, GGT, ALP and bilirubin. Significant improvements in ELF score (a marker of fibrosis), PRO-C3 (~20% reduction from baseline) and hsCRP (median reduction of 40% from baseline). Icosabutate was generally safe and well tolerated, with mild to moderate treatment emergent adverse events (TEAEs) and no reports of drug induced liver injury. As expected, icosabutate did not significantly decrease either liver fat or body weight. This aspect of icosabutate’s therapeutic profile may make it ideally suited for combination therapy in tandem with incretin-based therapies that successfully target body weight and liver fat. Pre-clinical studies have demonstrated the synergistic effects of GLP-1RA and icosabutate on hepatic fibrosis reduction. Rob de Ree, Chief Executive Officer of NorthSea Therapeutics, said, “We’re very pleased with the overall ICONA dataset. The MASH landscape has changed dramatically since we started the ICONA study. Firstly, the importance of improving fibrosis as the most clinically relevant and therapeutically challenging endpoint has become even more firmly entrenched. Secondly, the potential utility of artificial intelligence driven scoring as both a validated and alternative approach to conventional manual pathology has progressed rapidly. We believe there’s an important place for a safe, well-tolerated, oral anti-fibrotic with add-on benefits on glycemic control, inflammation and atherogenic lipids in the MASH therapeutic landscape, and we look forward to further developing icosabutate in more advanced MASH patients as a monotherapy or as a combination therapy.” About Phase 2b ICONA Clinical Trial The Phase 2b ICONA clinical trial was a 52-week randomized, double-blind, placebo-controlled trial that evaluated the safety and histological impact of icosabutate at 300 and 600 mg compared to placebo in 168 biopsy-confirmed MASH patients with moderate-to-severe fibrosis (stage F1, F2 or F3) with NAS ≥4. Patients were randomized to receive 300 mg or 600 mg icosabutate or placebo, taken orally once daily. An end-of-trial biopsy was assessed by 3 pathologists for histological endpoints using a consensus read approach. Liver biopsies were also analyzed using two independent AI-based digital pathology tools (pre-specified). About NorthSea Therapeutics NorthSea Therapeutics B.V. is a private, late-stage clinical biotechnology company developing novel strategies to treat metabolic, cholestatic, and fibrotic diseases. Its proprietary structurally engineered fatty acids (SEFAs) are designed to target key disease pathways, offering potential first-in-class treatments. With multiple clinical programs in progress, the company leverages a strong scientific foundation to drive innovation and advance new therapeutic approaches for diseases with serious unmet medical needs. NorthSea's $80M Series C financing was co-led by Ysios Capital and Forbion Growth and supported by venBio, Novo Seeds, Sofinnova, BGV and New Science Ventures. Headquartered in the Netherlands, NorthSea also has a presence in Norway and the U.S. To learn more, visit https://northseatherapeutics.com/en/ 1Stokman G, van den Hoek AM, Denker Thorbekk D, et al. Dual targeting of hepatic fibrosis and atherogenesis by icosabutate, an engineered eicosapentaenoic acid derivative. Liver Int. 2020;40(11):2860-76. 2Fraser DA, Wang X, Lund J, et al. A structurally engineered fatty acid, icosabutate, suppresses liver inflammation and fibrosis in NASH. J Hepatol. 2022;76(4):800-11. 3Iyer JS, Juyal D, Le Q, et al. AI-based automation of enrollment criteria and endpoint assessment in clinical trials in liver diseases. Nat Med. 2024;30(10):2914-23.