A Proof of Concept, Prospective, Randomized, Placebo-controlled, Double-blind, Study to Evaluate the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Patients With Primary Sclerosing Cholangitis

The objectives of this study is to Evaluate the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Patients with Primary Sclerosing Cholangitis

开始日期2025-06-01

申办/合作机构

Galmed Pharmaceuticals Ltd.

[+1]

NCT06502561

/ Active, not recruiting临床1期

A Phase 1 Relative Bioavailability Study Comparing The Pharmacokinetics Of Aramchol Meglumine Granules For Oral Suspension To Aramchol Free Acid 300 mg Tablets In Healthy Volunteers

This is a Phase 1 Relative Bioavailability Study Comparing The Pharmacokinetics Of Aramchol Meglumine Granules For Oral Suspension To Aramchol Free Acid 300 mg Tablets In Healthy Volunteers

开始日期2025-02-15

申办/合作机构

Galmed Pharmaceuticals Ltd.

NCT05874336

/ Completed临床1期

An Open-Label, Two-Part Study Designed to Assess the Absolute Bioavailability of Aramchol and to Determine the Mass Balance Recovery, Metabolite Profile and Metabolite Identification to Healthy Male Subjects

A two-part open-label study to assess the absolute bioavailability of aramchol and the mass balance recovery, metabolite profile and identification of metabolite structures for [14C]-aramchol in healthy male subjects

开始日期2020-06-17

申办/合作机构

Galmed Pharmaceuticals Ltd.

[+1]

100 项与 Icomidocholic acid 相关的临床结果

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100 项与 Icomidocholic acid 相关的转化医学

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100 项与 Icomidocholic acid 相关的专利（医药）

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项与 Icomidocholic acid 相关的文献（医药）

2025-03-01·HEPATOLOGY

Aramchol improves hepatic fibrosis in metabolic dysfunction–associated steatohepatitis: Results of multimodality assessment using both conventional and digital pathology

Article

作者: Eyal, Eli ; Cummings, Oscar W ; Petitjean, Mathieu ; Chen, Li ; Friedman, Scott L ; Yilmaz, Yusuf ; Lazas, Don ; Kadosh, Shaul ; Sanyal, Arun J ; Behling, Cynthia ; Gilgun-Sherki, Yossi ; Lackner, Caroline ; Ratziu, Vlad ; Gorfine, Tali

Background and Aims::

Antifibrotic trials rely on conventional pathology despite recognized limitations. We compared single-fiber digital image analysis with conventional pathology to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic dysfunction–associated steatohepatitis.

Approach and Results::

Fifty-one patients with metabolic dysfunction–associated steatohepatitis enrolled in the open-label part of the ARMOR trial received Aramchol 300 mg BID and had paired pre-post treatment liver biopsies scored by consensus among 3 hepatopathologists, and separately assessed by a digital image analysis platform (PharmaNest) that generates a continuous phenotypic Fibrosis Composite Severity (Ph-FCS) score. Fibrosis improvement was defined as: ≥1 NASH Clinical Research Network (NASH-CRN) stage reduction; “improved” by ranked pair assessment; reduction in Ph-FCS (“any” for ≥0.3 absolute reduction and “substantial” for ≥25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (ranked pair assessment), 74.5% (any Ph-FCS reduction), and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or ranked pair assessment had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks versus 39% for ≥48 weeks by NASH-CRN; 43% versus 61% by ranked pair assessment, mean Ph-FCS reduction −0.54 (SD: 1.22) versus −1.72 (SD: 1.02); Ph-FCS reduction (any in 54% vs. 100%, substantial in 21% vs. 65%). The antifibrotic effect of Aramchol was corroborated by reductions in liver stiffness, Pro-C3, and enhanced liver fibrosis. Changes in Ph-FCS were positively correlated with changes in liver stiffness.

Conclusions::

Continuous fibrosis scores generated in antifibrotic trials by digital image analysis quantify antifibrotic effects with greater sensitivity and a larger dynamic range than conventional pathology.

2024-07-31·Journal of Clinical and Translational Hepatology

Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease

Review

作者: Hu, Ye ; Fan, Jian-Gao ; Liu, Yu-Dong ; Sun, Chao ; Chen, Ying

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), the absence of licensed medications is striking. A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available medications. MASLD therapies center on four major pathways. Considering the close relationship between MASLD and type 2 diabetes, the first approach involves antidiabetic medications, including incretins, thiazolidinedione insulin sensitizers, and sodium-glucose cotransporter 2 inhibitors. The second approach targets hepatic lipid accumulation and the resultant metabolic stress. Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs. The third approach focuses on targeting oxidative stress, inflammation, and fibrosis. Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications.

2024-03-01·Journal of crop science and biotechnology

Comparison of metabolites between brown rice and germinated brown rice in a Korean weedy rice germplasm

作者: Cho, Ei Ei ; Chung, Nam-Jin

Weedy rice is a semi-wild species that has survived for a very long time in rice fields, so its seeds could contain more functional substances than cultivated rice.Addnl., during the process of seed germination, some physiol. active substances that were not present in the seed are newly synthesized, so the functional compounds of germinated seeds could be improved over those of untreated raw seeds.From this perspective, we evaluated metabolite compounds of the brown rice (BR) and germinated brown rice (GBR) of WD3 compared with a cultivated rice, Sindongjin (SDJ).WD3 is a weedy rice selected for antioxidant activity from 199 accessions of Korea-native weedy rice germplasm (Cho et al., J Crop Sci 63:219-228, 2018).Metabolites were measured by using UPLC coupled with tandem mass spectrometry.Pareto scaling method prior to statistical and chemometric anal. were used for data acquisition and processing for metabolize compoundsOPLS-DA was conducted to develop discriminatory models.To support the potential biomarkers identification and further understanding of this study, the information on compounds was queried on the Chemspider web page.The obvious separation of metabolites between WD3 and SDJ in both BR and GBR were observed, in which a total of 103 compounds were detected.Among them, 52 compounds were known and 51 compounds were unknown.In the known compounds, long aliphatic chains were commonly found and the others were steroids, alkaloids, polyols, peptide and aromatic acid.Some metabolites such as 3 alkaloid compounds, 2 steroids, 1 aromatic acid and 15 long aliphatic chains were significantly increased after germination in WD3 seeds.Among them, the content of C45H84NO7P was increased by more than 1,000,000 times after germination.These compounds found in the GBR of WD3 might also be correlated to the nutritionally qualities claimed to be responsible for the advantageous properties of GBR.

项与 Icomidocholic acid 相关的新闻（医药）

2025-05-22

·PRNewswire

Galmed Pharmaceuticals Reports First Quarter 2025 Financial Results and Provides Business Update

TEL AVIV, Israel, May 22, 2025 /PRNewswire/ -- Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) ("Galmed" or the "Company"), a clinical-stage biopharmaceutical company for cardiometabolic diseases and GI oncological indications, reports financial results for the three months ended March 31, 2025 and recent developments. Key Recent Developments Announced First Time Results in Oncology Studies: Aramchol Significantly Enhances Bayer's Regorafenib Effect in GI Cancer Models Signed Term Sheet for the Development of Novel Semaglutide Sublingual Formulation Raised $6.5 million since the beginning of 2025. Company's current cash balance is $20.1 million Financial Summary – First Quarter 2025 vs. First Quarter 2024*: Cash and cash equivalents, short term deposits, restricted cash and marketable debt securities totaled approximately $15.9 million as of March 31, 2025, compared to approximately $15.4 million at December 31, 2024. During May 2025, the Company raised an additional $5.0 million. As a result, as of the date hereof, the Company's current cash balance is approximately $20.1 million. Net loss amounted to approximately $1.1 million, or $0.62 per share, for the three months ended March 31, 2025, compared to a net loss of approximately $1.3 million, or $2.76 per share, for the three months ended March 31, 2024. Research and development expenses amounted to approximately $0.6 million for the three months ended March 31, 2025, compared to approximately $0.6 million for the three months ended March 31, 2024. General and administrative expenses amounted to approximately $0.6 million for the three months ended March 31, 2025, compared to approximately $0.8 million for the three months ended March 31, 2024. The decrease in general and administrative expenses for the three months ended March 31, 2023 resulted primarily from a decrease in professional services expenses. Financial income, net amounted to approximately $0.2 million for the three months ended March 31, 2025, compared to financial income of $0.1 million for the three months ended March 31, 2024. About Galmed Pharmaceuticals Ltd. We are a biopharmaceutical company focused on the development of Aramchol. We have focused almost exclusively on developing Aramchol for the treatment of liver disease and we are currently seeking to advance the development of Aramchol for oncological indications outside of NASH and fibrosis. In addition, as part of our growth strategy, we are actively pursuing opportunities to expand and diversify our product pipeline specifically targeting cardiometabolic indications and other innovative product candidates that align with our core expertise in drug development. Forward-Looking Statements: Forward-looking statements relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause our actual results to differ materially from any future results expressed or implied by the forward-looking statements. Forward-looking statements may include, but are not limited to, statements relating to our product development efforts, business, financial condition, results of operations, strategies or prospects, as well as statements, other than historical facts, that address activities, events or developments that we intend, expect, project, believes or anticipate will or may occur in the future. Many factors could cause our actual activities or results to differ materially from the activities and results anticipated in forward-looking statements, including, but not limited to, the development and approval of the use of Aramchol or any other product candidate for indications outside of non-alcoholic steatohepatitis, or NASH, also known as metabolic dysfunction-associated steatohepatitis, or MASH, and fibrosis or in combination therapy; the timing and cost of any pre-clinical or clinical trials of Aramchol or any other product candidate we develop; completion and receiving favorable results of any pre-clinical or clinical trial; regulatory action with respect to Aramchol or any other product candidate by the U.S. Food and Drug Administration, or the FDA, or the European Medicines Authority, or EMA, including but not limited to acceptance of an application for marketing authorization, review and approval of such application, and, if approved, the scope of the approved indication and labeling; the commercial launch and future sales of Aramchol and any future product candidates; our ability to comply with all applicable post-market regulatory requirements for Aramchol, or any other product candidate in the countries in which we seek to market the product; our ability to achieve favorable pricing for Aramchol, or any other product candidate; third-party payor reimbursement for Aramchol, or any other product candidate; our estimates regarding anticipated capital requirements and our needs for additional financing; market adoption of Aramchol or any other product candidate by physicians and patients; the timing, cost or other aspects of the commercial launch of Aramchol or any other product candidate; our ability to obtain and maintain adequate protection of our intellectual property; the possibility that we may face third-party claims of intellectual property infringement; our ability to manufacture our product candidates in commercial quantities, at an adequate quality or at an acceptable cost; our ability to establish adequate sales, marketing and distribution channels; intense competition in our industry, with competitors having substantially greater financial, technological, research and development, regulatory and clinical, manufacturing, marketing and sales, distribution and personnel resources than we do; our expectations regarding licensing, acquisitions and strategic operations; current or future unfavorable economic and market conditions and adverse developments with respect to financial institutions and associated liquidity risk; our ability to maintain the listing of our ordinary shares on The Nasdaq Capital Market; and security, political and economic instability in the Middle East that could harm our business, including due to the current security situation in Israel. We believe these forward-looking statements are reasonable; however, these statements are only current predictions and are subject to known and unknown risks, uncertainties and other factors that may cause our or our industry's actual results, levels of activity, performance or achievements to be materially different from those anticipated by the forward-looking statements. We discuss many of these risks in our Annual Report on Form 20-F for the year ended December 31, 2024 filed with the SEC on April 2, 2025 in greater detail under the heading "Risk Factors." Given these uncertainties, you should not rely upon forward-looking statements as predictions of future events. All forward-looking statements attributable to us or persons acting on our behalf speak only as of the date hereof and are expressly qualified in their entirety by the cautionary statements included in this report. We undertake no obligations to update or revise forward-looking statements to reflect events or circumstances that arise after the date made or to reflect the occurrence of unanticipated events. In evaluating forward-looking statements, you should consider these risks and uncertainties. * This unaudited preliminary financial information regarding the company's financial results for the three months and quarter ended March 31, 2025, is based upon the estimates and subject to completion of the company's quarter-end financial results. Moreover, this financial information has been prepared solely on the basis of currently available information by, and is the responsibility of, management. The company's independent registered public accounting firm has not audited, reviewed or performed any procedures with respect to such preliminary estimates or the accounting treatment thereof and does not express an opinion or any other form of assurance with respect thereto. This preliminary financial information is not a comprehensive statement of the company's financial results for this period. Logo: SOURCE Galmed Pharmaceuticals Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

财报

2025-04-10

·PRNewswire

Galmed Announces Positive Part 1 Results from the AM-001 Study of Aramchol Meglumine, an Enhanced Formulation of the Most Clinically Advanced SCD1 Inhibitor

– AM-001 Study represents a pivotal milestone in Galmed's transition to Aramchol Meglumine, an improved formulation of its lead compound in advanced clinical development – Aramchol Meglumine, a New Chemical Entity (NCE) protected by patents until 2035, is being developed both as a standalone agent and in novel drug combinations for multiple indications influenced by fatty acid metabolism – Initial findings suggest that the new Aramchol Meglumine formulation offers higher bioavailability than Aramchol free acid and that a once-daily, oral 200 mg dose is likely to be optimal for future trials, supporting improved patient compliance and potentially lowering manufacturing costs TEL AVIV, Israel, April 10, 2025 /PRNewswire/ -- Galmed Pharmaceuticals Ltd. (Nasdaq: GLMD) ("Galmed" or the "Company"), a clinical-stage biopharmaceutical company focused on liver, cardiometabolic, and gastrointestinal oncology indications, today announced positive preliminary results from Part 1 of the Ph1 Bioavailability AM-001 Study of Aramchol Meglumine. Galmed has successfully advanced Aramchol acid through six clinical trials (up to Ph3) enrolling 661 subjects, establishing both its overall safety and its efficacy in treating NASH (MASH). The N-methylglucamine (meglumine) salt of Aramchol exhibits notable advantages over Aramchol acid, including enhanced solubility, absorption, and systemic exposure, translating to higher bioavailability. In recognition of these benefits, Aramchol Meglumine received NCE patent protection extending until 2035. Previously, the FDA approved the transition from Aramchol acid to Aramchol Meglumine under a new IND, leveraging cross-reference to the substantial preclinical and clinical data amassed in recent years for Aramchol. The only requirement for this transition was a bioavailability study to compare the two formulations. The AM-001 study was conducted in response to that FDA request and is also designed to help identify the doses best suited for advancing Aramchol Meglumine into Phase 2 studies. It consists of two parts, comparing single doses of Aramchol acid and Aramchol Meglumine in healthy volunteers. Part 2 of the study is anticipated to conclude in the second half of 2025. In Part 1 of AM-001, preliminary results demonstrate that a 400 mg dose of Aramchol Meglumine suspension achieved an area under the curve (AUC) nearly double that of Aramchol acid tablets. Based on these outcomes, 200 mg once daily appears to be the optimal dose for subsequent clinical trials. This once-daily regimen not only simplifies patient adherence (moving from twice-daily to once-daily) but is also expected to reduce the overall cost of goods. "Aramchol is the most advanced down regulator of SCD-1 (Stearoyl – CoA desaturase) in clinical development. Inhibition of SCD-1 has been recently investigated in multiple indications, re-emphasizing its metabolic master switch potential and importance in multiple organs and functions. We expect that the long patent runway of Aramchol Meglumine will allow us to develop the full therapeutical potential of the drug in the planned expansion in cardiometabolic diseases and gastrointestinal cancers we recently announced," said Allen Baharaff, President and CEO of Galmed Pharmaceuticals. These latest Part 1 data reinforce Galmed's commitment to accelerating Aramchol Meglumine's clinical program. As seen with other biopharmaceutical companies that have successfully introduced improved formulations—often resulting in increased market interest—Galmed believes that Aramchol Meglumine's enhanced bioavailability, once-daily dosing, and robust patent protection position the Company favorably for continued growth. By building on its strong clinical foundation, Galmed aims to deliver innovative therapies for patients with significant unmet medical needs, while responsibly driving value for stakeholders. About Galmed Pharmaceuticals Ltd. We are a biopharmaceutical company focused on the development of Aramchol. We have focused almost exclusively on developing Aramchol for the treatment of liver disease and we are currently seeking to advance the development of Aramchol for oncological indications outside of NASH and fibrosis. In addition, as part of our growth strategy, we are actively pursuing opportunities to expand and diversify our product pipeline specifically targeting cardiometabolic indications and other innovative product candidates that align with our core expertise in drug development. Forward-Looking Statements: Forward-looking statements relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause our actual results to differ materially from any future results expressed or implied by the forward-looking statements. Forward-looking statements may include, but are not limited to, statements relating to our product development efforts, business, financial condition, results of operations, strategies or prospects, including the timing of completion of the AM 001 study, as well as statements, other than historical facts, that address activities, events or developments that we intend, expect, project, believes or anticipate will or may occur in the future. Many factors could cause our actual activities or results to differ materially from the activities and results anticipated in forward-looking statements, including, but not limited to, the development and approval of the use of Aramchol or any other product candidate for indications outside of non-alcoholic steatohepatitis, or NASH, also known as metabolic dysfunction-associated steatohepatitis, or MASH, and fibrosis or in combination therapy; the timing and cost of any pre-clinical or clinical trials of Aramchol or any other product candidate we develop; completion and receiving favorable results of any pre-clinical or clinical trial; regulatory action with respect to Aramchol or any other product candidate by the U.S. Food and Drug Administration, or the FDA, or the European Medicines Authority, or EMA, including but not limited to acceptance of an application for marketing authorization, review and approval of such application, and, if approved, the scope of the approved indication and labeling; the commercial launch and future sales of Aramchol and any future product candidates; our ability to comply with all applicable post-market regulatory requirements for Aramchol, or any other product candidate in the countries in which we seek to market the product; our ability to achieve favorable pricing for Aramchol, or any other product candidate; third-party payor reimbursement for Aramchol, or any other product candidate; our estimates regarding anticipated capital requirements and our needs for additional financing; market adoption of Aramchol or any other product candidate by physicians and patients; the timing, cost or other aspects of the commercial launch of Aramchol or any other product candidate; our ability to obtain and maintain adequate protection of our intellectual property; the possibility that we may face third-party claims of intellectual property infringement; our ability to manufacture our product candidates in commercial quantities, at an adequate quality or at an acceptable cost; our ability to establish adequate sales, marketing and distribution channels; intense competition in our industry, with competitors having substantially greater financial, technological, research and development, regulatory and clinical, manufacturing, marketing and sales, distribution and personnel resources than we do; our expectations regarding licensing, acquisitions and strategic operations; current or future unfavorable economic and market conditions and adverse developments with respect to financial institutions and associated liquidity risk; our ability to maintain the listing of our ordinary shares on The Nasdaq Capital Market; and security, political and economic instability in the Middle East that could harm our business, including due to the current security situation in Israel. We believe these forward-looking statements are reasonable; however, these statements are only current predictions and are subject to known and unknown risks, uncertainties and other factors that may cause our or our industry's actual results, levels of activity, performance or achievements to be materially different from those anticipated by the forward-looking statements. We discuss many of these risks in our Annual Report on Form 20-F for the year ended December 31, 2024 filed with the SEC on April 2, 2025 in greater detail under the heading "Risk Factors." Given these uncertainties, you should not rely upon forward-looking statements as predictions of future events. All forward-looking statements attributable to us or persons acting on our behalf speak only as of the date hereof and are expressly qualified in their entirety by the cautionary statements included in this report. We undertake no obligations to update or revise forward-looking statements to reflect events or circumstances that arise after the date made or to reflect the occurrence of unanticipated events. In evaluating forward-looking statements, you should consider these risks and uncertainties. Logo - SOURCE Galmed Pharmaceuticals Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果临床1期上市批准

2024-10-28

·药智网

2024年集体爆发的MASH市场，竞争格局几何？

继今年3月，全球首款MASH新药——Resmetirom获FDA批准用于治疗伴有肝纤维化的成人MASH患者，填补了MASH药物的空白状态后，近段时间以来，国内MASH领域的“新药曝光度”有目共睹的在增加。 10月15日，微芯生物宣布，其研发的西格列他钠治疗非酒精性脂肪性肝炎（NASH）/代谢相关性脂肪性肝炎（MASH）的2期临床研究（CGZ203试验）摘要入选美国肝病研究学会年会（AASLD 2024），11月17日以口头报告形式公布。 10月18日，中国国家药监局药品审评中心（CDE）官网公示，康弘药业1类THR-β新药KH629片获得临床试验默示许可，拟开发用于治疗成人非酒精性脂肪性肝炎。为何沉寂40余年的MASH新药研究，短时间内俨然成为“流量”的代名词，成为众多药企争相入局的潜力市场，其背后又是怎样的底层逻辑使然？患病率高涨 MASH是临床需求愈发迫切其实，与大多数肝脏慢性病不同，近年来非酒精性脂肪性肝病（NAFLD）的患病率不降反增，现阶段已取代乙肝成为我国最常见的慢性肝病。资料显示，中国成年人中NAFLD患病率高达29.2%，10年内整体增长10%，中国MASH患病率约为2.4%～6.1%，我国NAFLD/MASH患者疾病负担极其沉重。据弗若斯特沙利文报告预计， 2030 年全球 MASH 患病人数将达到 4.9 亿人，全球MASH药物市场将达到 322 亿美元。作为NAFLD中最严重的发展阶段，原理上MASH是一种与代谢紊乱相关的肝脏疾病，其特征是肝脏中脂肪的异常积累，伴随着炎症和肝细胞损伤，早年间被称为非酒精性脂肪性肝炎（NASH）。 40余年的相关研究下，人们对MASH的发病机制仍尚未完全明确，目前认为其乃是一种代谢应激性肝损伤，与多种因素相关，复杂的级联反应下的肝细胞损伤机制有以下几种，主要包括胰岛素抵抗、氧化应激、炎症反应和脂质代谢异常等多个环节。在临床表现方面，MASH通常情况下起病隐匿且缓慢，且通常无症状，多于常规检查过程中无意发现，并且由于MASH通常情况下难以自发缓解，在早期无干预的情况下进展为肝纤维化的风险很高，大约有15%的患者会发展为肝硬化、肝衰竭和肝细胞癌。临床药物缺乏 MASH传统治疗局限性大在Resmetirom获FDA批准上市之前，全球尚无治疗 NAFLD/NASH 的靶向性药物，而由于MASH与肥胖、2 型糖尿病、高血压、血脂紊乱等疾病的密切相关性，目前普遍认为控制这些疾病可有效改善 NAFLD/NASH的代谢状态，从而延缓疾病进展。因此，NAFLD以及MASH的治疗基础仍是生活方式的干预和饮食方案的优化，生活习惯的改善，尤其饮食的控制及锻炼减重等可减少肝脏脂肪沉积，有利于改善 MASH 的生化指标和肝组织学病变，相关研究显示，体重减轻 3% 即可改善 NAFLD患者脂肪肝病情程度，减重 7% 可改善肝脏炎症等组织学指标，减重 10% 可逆转肝纤维化水平。而在药物治疗方面，临床上主要针对抗胰岛素抵抗、抗氧化应激、降血脂、促进脂质代谢及保护肝细胞膜等对MASH进行治疗，如二甲双胍、维生素 E、熊去氧胆酸、FXR激动剂奥贝胆酸、肝损伤治疗药物等保肝药物的使用。但同时，上述药物治疗方式的局限性也很大，一者药物的治疗剂量、有效性及安全性均尚不明确，有待进一步研究；二者，如奥贝胆酸等FXR激动剂的不良反应也极大限制了其在MASH领域的应用。故现阶段的MASH临床治疗上，迫切需要一种副作用低、能逆转肝纤维化、患者顺应性佳的创新疗法。四大方向推动MASH机制逐渐清晰就目前而言，通过对MASH的发病机制研究，目前已有多款靶点给予了MASH有效干预，是目前乃至未来MASH治疗的主要方向。从类型上来看主要分为代谢、消化、抗炎、抗纤维化四种方向：代谢类：改善胰岛素敏感性、抑制脂肪生成各种酶、促进线粒体摄取脂肪酸等。消化类：调控肝肠轴的循环、改善胆汁酸的循环与信号传导、改善肠道菌群的平衡等。抗炎类：抑制炎症细胞聚集、阻断炎性信号传导、降低氧化作用和内质网应激反应、防止肝细胞凋亡等。抗纤维化：针对肝脏中的星形细胞、减轻肝脏中胶原蛋白的沉积、增强纤维分解等。而在这四种类型药物之下，又可以细分出不同的靶点选择，各靶点方向之下又存在不同的技术优势与产品差异。数据来源：公开数据整理（点击查看大图）据不完全统计，全球现有MASH在研疗法已突破350款。其中代谢类与消化类的数量最多，而前者主要机制集中于肝内，在逆转纤维化方面具有优势，而后者则是从肝外机制着手，在降低肝脏脂肪积累与纤维化进展方面优势明显，两者机制各有优劣，未来大概率会是协同合作的关系。临床阶段方面，虽绝大多数创新疗法均集中在临床前阶段，但跨入临床阶段的产品依旧不少，其中以临床II期管线数量最多，共计108款；而进入临床III期产品则也有18款之多。表1.MASH临床III期管线药品名称靶点适应症最高阶段原研单位利莫纳班 rimonabant CB1 临床Ⅲ期赛诺菲依碳酸瑞格列净 remogliflozin etabonate SLC5A2 临床Ⅲ期 BHV Pharma Inc;格兰马克制药有限公司沙格列扎镁 aroglitazar magnesium INS 临床Ⅲ期 Zydus Lifesciences Ltd 司美格鲁肽 semaglutide GLP-1R 临床Ⅲ期丹麦诺和诺德公司腺苷蛋氨酸 ademetionine Transferase 临床Ⅲ期雅培制药芦比前列酮 lubiprostone CFTR;ClC-2;PGE1 临床Ⅲ期 Sucampo Pharma LLC 佩玛贝特 pemafibrate PPAR-alpha 临床Ⅲ期 Kowa Co Ltd 塞拉德帕 seladelpar PPAR-delta 临床Ⅲ期 CymaBay Therapeutics Inc;强生创新制药 aramchol SCD1 临床Ⅲ期 Galmed Pharmaceuticals Ltd survodutide GLP-1R;GCGR 临床Ⅲ期 Zealand Pharma A/S;勃林格殷格翰 FXR314 NR1H4 临床Ⅲ期 Organovo Holdings inc 拉尼兰诺 lanifibranor PPAR-alpha;PPAR-delta;PPAR-gamma 临床Ⅲ期 Inventiva 可妥度肽 cotadutide GLP-1;GCGR 临床Ⅲ期阿斯利康瑟隆舍替selonsertib MAP3K5 临床Ⅲ期美国吉利德科学公司塞尼韦洛 cenicriviroc CCR2;CCR5 临床Ⅲ期 Tobira Therapeutics Inc;武田药品工业株式会社 ENB-106 / 临床Ⅲ期上海轶诺药业有限公司依鲁西夫明 efruxifermin FGF21 临床Ⅲ期安进公司 norucholic acid / 临床Ⅲ期德国霍克大药厂数据来源：药智数据三大靶点引领MASH新药加速落地就MASH在研药物靶点分布上而言，glp-1、FXR、THR-β、FGF19/21与PPAR是现阶段MASH最主要的在研药物类型。数据来源：药智数据从数量上来看，FXR激动剂、GLP1在研发热度上远超其他靶点，其在研数量也最多，目前均有超过30款相关疗法布局；其次是THR-β、FGF19/21与PPAR，分别有19、18与13款新药布局；其余靶点数量则相对较少，其临床阶段也相对靠后。从趋势上来看，FXR激动剂虽然是MASH领域的老牌靶点之一，但由于靶点特殊作用机制，其在副作用上的局限性太大，直接影响了其在临床上的应用潜力。至少就现在而言，反而是glp-1与THR-β两种机制的MASH新药更受关注，未来也更容易占据头牌。数据来源：药智数据 GLP-1 由于原理上GLP-1类似物能够有效改善糖脂代谢异常，因此GLP-1受体激动剂在糖尿病与减重适应症外，也被视为潜在的MASH治疗药物。表2.GLP-1应用于MASH的创新疗法药品名称靶点原研单位适应症最高阶段司美格鲁肽 semaglutide GLP-1R 丹麦诺和诺德公司临床Ⅲ期 survodutide GLP-1R;GCGR Zealand Pharma A/S;勃林格殷格翰临床Ⅲ期可妥度肽 cotadutide GLP-1;GCGR 阿斯利康临床Ⅲ期替尔泊肽 tirzepatide GIPR;GLP-1R 礼来制药临床Ⅱ期 RAY-1225 GLP-1;GIP 广东众生睿创生物科技有限公司临床Ⅱ期 HEC-88473 FGF21;GLP-1R 东莞市东阳光生物药研发有限公司临床Ⅱ期派维度肽 pemvidutide GLP-1R;GCGR Altor BioScience Corp合作：Altimmune Inc 临床Ⅱ期尤曲格鲁肽 utreglutide GLP-1R 印度太阳药业有限公司临床Ⅱ期巴度肽 bamadutide GLP-1R;GCGR 赛诺菲临床Ⅱ期依福培肽 efocipegtrutide GIPR;GLP-1R;GCGR 韩美药品株式会社临床Ⅱ期数据来源：药智数据截止目前，随着人们对 GLP-1 的焦点由减肥向在抗 MASH转变之下，已有超30种GLP-1药物正在研究其治疗MASH的潜力，临床上推进较快的产品不少，较出名的产品有诺和诺德的司美格鲁肽、勃林格殷格翰的survodutide、阿斯利康的cotadutide、礼来制药的tirzepatide。其中，Semaglutide与替尔泊肽作为GLP-1两大重磅产品，在关于MASH的治疗研究中均显示出减少肝脏脂肪积累、降低炎症水平的潜力，极大地振奋了行业对GLP-1作用于MASH的信心。但与此同时，GLP-1在治疗MASH上的局限性也逐渐体现，即虽然在减少肝脏脂肪积累和纤维化方面的效果显著，但对逆转肝脏纤维化上却缺乏足够、全面、多维度的有效证据。这就导致GLP-1疗法单药治疗既无法完全满足现有的临床需求，也很难与其他疗法拉开差距。对此，有关人士表示，GLP-1未来要想在MASH领域站稳脚跟，要么就逆转纤维化做出更多差异化成果，要么依靠肝外机制改善代谢紊乱的特点，与众多肝内机制的MASH疗法形成联动与互补，以协同策略解决MASH的临床需求。 Fxr（NR1H4）作为曾经治疗MASH最重要的靶点，也是MASH早期阶段最主要的在研药物形式，FXR作为一种肠肝调节因子，不仅参与胆汁酸信号传导，调控胆汁酸合成和转运，还可以调节葡萄糖稳态、脂质和胆固醇代谢等其他生理功能以及抑制炎症，在MASH治疗上，目前已显示出一定的治疗效果。截止目前，除已经宣布终止MASH适应症开发的奥贝胆酸外，领域内仍有超过30款Fxr激动剂涉及MASH适应症，其中Organovo的FXR314已进入了临床III期，是现阶段推进最快的Fxr激动剂；之后，还有10余款管线进入了临床II期，较受期待的有吉利德的cilofexor、诺华制药的nidufexor、东阳光药业HEC96719等。表3.MASH中Fxr激动剂创新疗法药品名称靶点原研单位适应症最高阶段奥贝胆酸 obeticholic acid NR1H4 Intercept Pharmaceuticals Inc 注册申请 FXR314 NR1H4 Organovo Holdings inc 临床Ⅲ期昔洛法克索 cilofexor NR1H4 Phenex Pharmaceuticals AG;美国吉利德科学公司临床Ⅱ期尼度法克索 nidufexor NR1H4 诺华制药临床Ⅱ期 HEC96719 NR1H4 广东东阳光药业股份有限公司临床Ⅱ期卓匹非索 tropifexor NR1H4 诺华制药临床Ⅱ期 CS-0159 NR1H4 Van Andel Institute;中国科学院上海药物研究所;凯思凯迪（上海）医药科技有限公司临床Ⅱ期 EDP-305 NR1H4 Enanta Pharmaceuticals Inc 临床Ⅱ期 TERN-101 NR1H4 上海拓臻生物科技有限公司;礼来制药临床Ⅱ期 MET-642 NR1H4 Metacrine Inc 临床Ⅱ期 MET-409 NR1H4 Metacrine Inc 临床Ⅱ期 HPG1860 NR1H4 雅创医药技术（上海）有限公司临床Ⅱ期 EYP-001 NR1H4 Poxel SA 临床Ⅱ期数据来源：药智数据而与此同时，虽然近年来Fxr激动剂领域用于MASH治疗的研究开发正在进入快速发展期，但临床获益有限，副作用严重等局限性也制约了其在临床上应用，最显著的例子就是奥贝胆酸，其2015年获FDA突破性疗法资格认定，是全球第一个进入临床3期的MASH候选产品，但最终仍因获益不确定性、副作用较大而折戟，经历多次被FDA否决后，最终无奈宣布终止其用于MASH领域的开发。因此，对于Fxr激动剂整体而言，在保证创新疗法的有效性，研究机构未来更大的精力或将集中于创新疗法的不良反应的减少与安全性的提高上。 THR-β THR-β是一种核激素受体，其主要在肝脏中高表达，能够调节脂代谢，降低低密度脂蛋白胆固醇（LDL-C）、甘油三酯和致动脉粥样硬化性脂蛋白，因此成为理论上MASH最具潜力的治疗靶点。此外，THR-β还可以通过促进脂肪酸的分解和刺激线粒体的生物发生来减少脂肪毒性并改善肝功能，进而减少肝脏脂肪。这也是为何THR-β激动剂会具备调控多种肝脏代谢通路来治疗MASH的潜力的原因。其在MASH上的主要作用有以下5点：调控脂肪合成调控脂肪酸氧化作用调控胆固醇代谢调控线粒体功能通过抑制TGF-β信号通路发挥抗炎和抗纤维化作用 2024年3月，Resmetirom成为首款获FDA批准上市的治疗代谢功能障碍相关脂肪性肝炎（MASH）的新药，也是THR-β激动剂领域首款撞线的产品。表4.MASH中THR-β激动剂创新疗法药品名称靶点原研单位适应症最高阶段瑞司美替罗 resmetirom THRB Madrigal Pharmaceuticals Inc;罗氏制药批准上市 VK-2809 THRB Ligand Pharmaceuticals Inc;Viking Therapeutics Inc 临床Ⅱ期 ASC41 THRB 歌礼制药有限公司;甘莱制药有限公司临床Ⅱ期 TERN-501 THRB 上海拓臻生物科技有限公司临床Ⅱ期 HSK-31679 THRB 海思科医药集团股份有限公司临床Ⅱ期 ALG-055009 THRB Aligos Therapeutics Inc 临床Ⅰ期 ASC-43-F THRB;NR1H4 歌礼制药有限公司;甘莱制药有限公司临床Ⅰ期 RJ-4287 THRB 南京奥利墨斯医药科技有限公司临床Ⅰ期 Kylo-0603 THRB 厦门甘宝利生物医药有限公司临床Ⅰ期 CS-060304 THRB 凯思凯迪（上海）医药科技有限公司临床Ⅰ期 CS-060380 THRB 凯思凯迪（上海）医药科技有限公司临床Ⅰ期数据来源：药智数据 Resmetirom的成功获批一方面为MASH患者的治疗提供了新手段，同时另一方面也证明了THR-β激动剂路线的可行性。也正是因此，THR-β激动剂成为全球MASH新药研发的主要集中方向，多款THR-β激动剂紧随其后，均表现出不俗的潜力，目前临床阶段进展较快的主要有四款，分别是Ligand的VK-2809、歌礼制药的ASC41、拓臻生物的TERN-501以及海思科的HSK-31679，均已进入了临床II期。而更值得注意的是，THR-β激动剂也是目前国内MASH在研新药最集中的方向，处于领先地位（临床进度靠前）的创新疗法数量远高于其他几种类型。未来，不出意外的话，国内在该领域的突破大概率也将集中此，或许还有望领先于海外药企，成为MNC争夺的关键。小结纵观MASH领域40余年的发展历史，从致病机制的不断完善，到临床上的对症治疗出现，再到今年首款新药获批上市，MASH的新药研发充满坎坷。但随着MASH新药研发的四大机制方向、10余款创新靶点的逐步落地，领域内似乎正在逐渐形成一个系统化、宏观化的研发格局，过程中不断有更多如GLP-1、THR-β等全新的疗法加入，至少目前看来俨然一副百废待兴，可大展拳脚的状态。而对于国内药企而言，虽然某种程度上做不到如海外一般全赛道布局，但在个别如THR-β激动剂等潜力领域的优势却反而更大，或许这种强调聚焦的国内赛道模式，未来或许真能让中国企业站上国际舞台，成为MASH领域的龙头之一。来源 | 博药（药智网获取授权转载）撰稿 | 头孢责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

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100 项与 Icomidocholic acid 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
纤维化	临床3期	以色列	Galmed Pharmaceuticals Ltd.	2024-02-26
非酒精性脂肪性肝炎	临床3期	美国	Galmed Research & Development Ltd.	2019-09-23
原发性硬化性胆管炎	临床2期	美国	Galmed Pharmaceuticals Ltd.	2025-06-01
HIV感染	临床2期	美国	University of California San Diego	2016-01-01
脂肪营养不良	临床2期	美国	University of California San Diego	2016-01-01
代谢功能障碍相关的脂肪肝病	临床2期	美国	University of California San Diego	2016-01-01
胆结石	临床2期	以色列	Galmed Pharmaceuticals Ltd.	2014-10-01
代谢综合征	临床2期	以色列	Galmed Medical Research Ltd.	2010-11-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AM-001 (PRNewswire) 人工标引	临床1期	-	-	Aramchol Meglumine	觸憲壓觸網網窪齋鏇遞(醖鬱艱顧夢窪構製積艱) = preliminary results demonstrate that a 400 mg dose of Aramchol Meglumine suspension achieved an area under the curve (AUC) nearly double that of Aramchol acid tablets. 選製築窪築築積襯鬱鑰 (餘襯鹽築顧簾糧艱餘網 )	积极	2025-04-10
				Aramchol free acid
NCT04104321 (ARMOR, CTgov)	临床3期	非酒精性脂肪性肝炎	157	Aramchol (Aramchol)	夢選製齋鹽鏇選繭觸艱 = 壓壓餘醖鹽餘鹹蓋廠衊製糧網願網廠糧範糧鑰 (廠衊廠遞鹹遞膚遞廠鑰, 鹹衊窪顧鏇膚鏇願鹹鏇 ~ 蓋顧範願窪夢積糧構鬱) 更多	-	2024-12-16
				Aramchol (Patients Randomized to the OL Part of the ARMOR Study)	壓齋鹽窪糧窪襯製窪齋(遞範齋範鹹膚鹽顧繭餘) = 積遞夢醖衊範襯願願醖築齋鏇齋繭醖選膚襯齋 (憲糧範鹹憲蓋繭窪選鑰, 觸範積積獵觸鹹鏇蓋窪 ~ 醖鹹構艱蓋窪築壓網鹽) 更多
NCT04480827 (CTgov)	临床1期	肝功能不全	57	Aramchol free acid tablet 600mg, single dose (Part 1: Mild Hepatic Impairment (Cohort A))	衊壓繭餘鏇鏇艱構築鹹(鑰糧窪艱築製遞製淵範) = 艱選築醖範遞齋獵襯鑰獵繭積鹹願願構膚醖艱 (窪鑰鹹範願淵鑰醖憲鏇, 138.29) 更多	-	2024-08-14
				Aramchol free acid tablet 600mg, single dose (Part 1: Moderate Hepatic Impairment (Cohort B))	衊壓繭餘鏇鏇艱構築鹹(鑰糧窪艱築製遞製淵範) = 淵製鹽遞鹹製繭餘遞製獵繭積鹹願願構膚醖艱 (窪鑰鹹範願淵鑰醖憲鏇, 154.13) 更多
NCT04104321 (ARMOR, EASL2022)	临床3期	纤维化 ALT \| AST \| Fib-4 ... 更多	150	Aramchol 300 mg BID	窪襯獵襯範壓選膚憲膚(廠製鏇艱齋壓衊壓衊淵) = 襯築蓋獵鹹鑰顧鬱簾獵壓窪衊膚齋築選鏇積積 (繭遞範醖餘廠網膚願構 )	积极	2022-06-24
ARMOR STUDY (NASH_TAG2022)	临床3期	纤维化 ALT \| AST \| Fib-4 ... 更多	150	Aramchol 300mg BID	蓋製鬱顧願網製鹽憲襯(齋築齋夢繭膚構夢鹽衊) = 簾構糧遞觸簾選窪淵夢醖鹹獵蓋製製鏇顧鏇憲 (範餘淵淵齋糧製夢鬱窪 )	积极	2022-01-06
				Placebo	蓋製鬱顧願網製鹽憲襯(齋築齋夢繭膚構夢鹽衊) = 糧淵壓觸築鏇齋鏇窪襯醖鹹獵蓋製製鏇顧鏇憲 (範餘淵淵齋糧製夢鬱窪 )
NCT02279524 (ARREST, Pubmed \| Nat Med) 人工标引	临床2期	非酒精性脂肪性肝炎	247	Aramchol 600mg	襯淵鹹憲醖廠齋積遞顧(鏇醖壓顧齋鹹鬱壓網顧) = 築製築遞製艱鬱襯憲衊壓觸衊願簾鑰餘製鏇蓋 (製憲積簾淵選製獵淵築, -6.4 ~ 0.2) 更多	积极	2021-10-01
				Placebo	夢願廠窪壓蓋簾範簾繭(衊糧範獵廠觸積餘齋窪) = 蓋淵鬱構獵醖網繭製觸範窪壓鏇築夢夢簾網積 (淵願艱網醖齋襯顧築醖 ) 更多
NCT02279524 (ARREST \| Aramchol_005, CTgov)	临床2期	非酒精性脂肪性肝炎	247	Aramchol (Aramchol 600mg)	顧獵夢齋願願網廠憲齋(網範鬱觸顧築遞繭糧觸) = 築鹹獵憲餘窪艱選餘願餘觸網膚鹽蓋顧糧繭壓 (顧鹹構構鬱醖鏇願膚顧, 1.01) 更多	-	2021-07-14
				Aramchol (Aramchol 400mg)	顧獵夢齋願願網廠憲齋(網範鬱觸顧築遞繭糧觸) = 廠繭構築願膚夢淵廠壓餘觸網膚鹽蓋顧糧繭壓 (顧鹹構構鬱醖鏇願膚顧, 0.96) 更多
NCT02684591 (ARRIVE, Pubmed \| Hepatology) 人工标引	临床2期	代谢功能障碍相关的脂肪肝病	50	Aramchol	構觸鹹範範膚齋蓋顧膚(齋窪壓簾窪淵衊簾製憲) = 餘製鏇網衊醖構鬱淵鹽鹹鬱糧糧網衊衊遞鬱簾 (選願獵網衊選鬱夢觸網 ) 更多	不佳	2019-11-01
				Placebo	構觸鹹範範膚齋蓋顧膚(齋窪壓簾窪淵衊簾製憲) = 蓋鹽選積觸鏇繭壓艱遞鹹鬱糧糧網衊衊遞鬱簾 (選願獵網衊選鬱夢觸網 ) 更多
NCT02684591 (ARRIVE \| ARRIVE Trial, CTgov)	临床2期	脂肪营养不良 \| HIV感染 \| 代谢功能障碍相关的脂肪肝病	50	Aramchol (Aramchol 600 mg Orally Daily)	醖廠壓膚構淵構鏇積鑰(膚網艱鹽齋鬱膚膚餘選) = 壓壓鑰齋積鑰網糧壓淵窪構齋製窪餘淵膚製壓 (築蓋淵繭網鏇製鏇糧築, 構廠觸鹽糧蓋壓網窪範 ~ 膚顧觸衊窪製餘顧膚觸) 更多	-	2019-08-21
				Placebo (Placebo)	醖廠壓膚構淵構鏇積鑰(膚網艱鹽齋鬱膚膚餘選) = 餘蓋願鑰積製壓憲醖蓋窪構齋製窪餘淵膚製壓 (築蓋淵繭網鏇製鏇糧築, 積鹽構顧餘齋窪鹽憲壓 ~ 製簾築構膚齋範鏇繭夢) 更多
NCT01094158 (Pubmed \| Clin Gastroenterol Hepatol)	临床2期	代谢功能障碍相关的脂肪肝病	60	Placebo	艱製壓繭簾繭餘夢網夢(膚糧簾簾網範壓鬱鏇艱) = 繭獵餘鹽鹽艱顧壓鏇鏇鬱糧醖糧淵範廠餘遞網 (遞醖製繭網選蓋淵繭憲 )	-	2014-12-01