A Phase 1, Open-label, Randomized, Two-Part Study to Assess the Safety and Pharmacokinetics of Tablet and Capsule Formulations of HU6 in Healthy Subjects.

This is a 2-part study. Part 1 will assess the relative bioavailability of the new 450 mg tablet test formulation compared to the 150 mg capsule reference formulation (3 x 150 mg). Part 1 dosing will be conducted in the fasted state. Part 2 will assess the effect of food (and fat content) on the pharmacokinetics of the 450 mg tablet test formulation.

开始日期2024-07-24

申办/合作机构

Rivus Pharmaceuticals, Inc.

NCT06325930

/ Completed临床1期

An Open-Label Phase 1 Study in Healthy Adult Male Subjects to Investigate the Absorption, Metabolism, and Excretion of [14C]-HU6 Following Single-Dose Oral Administration

This is a single-center, non-randomized, open-label Phase 1 study to characterize the absorption, metabolism, excretion, mass balance, pharmacokinetics (PK), safety and tolerability of HU6 following administration of a single dose of [14C]-HU6 in a fed state with a standard meal administered approximately 15 minutes prior to dosing.

开始日期2024-03-26

申办/合作机构

Rivus Pharmaceuticals, Inc.

NCT06104358

/ Withdrawn临床2期

A 6-Month, Randomized, Double-Blind, Placebo-controlled, Phase 2a Study of the Effects of HU6 on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function in Subjects Who Are Overweight or Obese With Type 2 Diabetes

This is a randomized, double-blind, placebo-controlled parallel group study of HU6 and placebo in subjects who are overweight or obese with T2D.
The study will be conducted in 4 stages.

开始日期2023-11-17

申办/合作机构

Rivus Pharmaceuticals, Inc.

100 项与 HU-6 相关的临床结果

登录后查看更多信息

100 项与 HU-6 相关的转化医学

登录后查看更多信息

100 项与 HU-6 相关的专利（医药）

登录后查看更多信息

项与 HU-6 相关的文献（医药）

2023-12-01·The lancet. Gastroenterology & hepatology

Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial

Article

作者: Sanyal, Arun J ; Dennis, Jameel ; Khan, Omer ; Johansson, Edvin ; Portell, Francisco ; Jorkasky, Diane ; Khan, Shaharyar ; Noureddin, Mazen ; Johansson, Lars

BACKGROUND:

HU6 is a controlled metabolic accelerator that is metabolised in the liver to the mitochondrial uncoupler 2,4-dinitrophenol and increases substrate utilisation so that fat and other carbon sources are oxidised in the body rather than accumulated. We aimed to assess the safety and efficacy of HU6 compared with placebo in people with non-alcoholic fatty liver disease (NAFLD) and high BMI.

METHODS:

This randomised, double-blind, placebo-controlled, phase 2a trial was done at a single community site in the USA. Adults (aged 28-65 years) with a BMI of 28-45 kg/m², a FibroScan controlled attenuation parameter score of more than 270 decibels per metre, and at least 8% liver fat by MRI-proton density fat fraction (MRI-PDFF) were randomly assigned (1:1:1:1) to receive, under fasting conditions, either once-daily HU6 100 mg, HU6 300 mg, HU6 450 mg, or matching placebo by oral administration for 61 days. Randomisation was blocked (groups of four) and stratified by baseline glycated haemoglobin (<5·7% vs ≥5·7%; 39 mmol/mol). All participants and study personnel involved with outcome assessments were masked to treatment assignment. The primary endpoint was the relative change in liver fat content from baseline to day 61, as assessed by MRI-PDFF, and was analysed in the full analysis set (FAS), which comprised all participants who were randomly assigned, received at least one dose of treatment, and had less than 4·5 kg of weight gain or weight loss from the time of screening to day 1 of treatment. The safety population included all participants who were randomly assigned and received at least one dose of study drug. This study was registered at ClinicalTrials.gov, NCT04874233, and is complete.

FINDINGS:

Between April 28, 2021, and Nov 29, 2021, 506 participants were assessed for eligibility and 80 adults (39 [49%] women and 41 [51%] men) were enrolled and randomly assigned to placebo (n=20), HU6 150 mg (n=20), HU6 300 mg (n=21), or HU6 450 mg (n=19). One participant in the HU6 450 mg group was excluded from the FAS due to weight gain. Relative mean change in liver fat content from baseline to day 61 was -26·8% (SD 17·4) for the HU6 150 mg group, -35·6% (13·8) for the HU6 300 mg group, -33·0% (18·4) for the HU6 450 mg group, and 5·4% (19·8) for the placebo group. Three people treated with HU6 (two treated with 150 mg and one treated with 300 mg) and two people treated with placebo discontinued treatment due to treatment-emergent adverse events (TEAEs). No serious TEAEs were reported. In those treated with HU6, flushing (19 [32%] participants), diarrhoea (15 [25%] participants), and palpitations (seven [12%] participants) were the most frequently reported TEAEs (in the placebo group, two [10%] participants had flushing, none had diarrhoea, and one [5%] had palpitations). There were no deaths.

INTERPRETATION:

HU6 could be a promising pharmacological agent for treating patients with obesity and NAFLD and its metabolic complications.

FUNDING:

Rivus Pharmaceuticals.

2006-12-01·BMC microbiology3区 · 生物学

Cytokine responses of bovine macrophages to diverse clinical Mycobacterium avium subspecies paratuberculosis strains

3区 · 生物学

ArticleOA

作者: Paul M. Coussens ; Vivek Kapur ; Harish K Janagama ; Srinand Sreevatsan ; Kwang il Jeong

Abstract:

Background:

Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's disease (JD) persistently infects and survives within the host macrophages. While it is established that substantial genotypic variation exists among MAP, evidence for the correlates that associate specific MAP genotypes with clinical or sub-clinical disease phenotypes is presently unknown. Thus we studied strain differences in intracellular MAP survival and host responses in a bovine monocyte derived macrophage (MDM) system.

Results:

Intracellular survival studies showed that a bovine MAP isolate (B1018) and a human MAP isolate (Hu6) persisted in relatively higher numbers when compared with a sheep MAP isolate (S7565) at 24-hr, 48-hr and 96-hr post infection (PI). MDMs stimulated with B1018 up-regulated IL-10 at the transcript level and down-regulated TNFα at the protein and transcript levels compared with stimulations by the S7565 and Hu6. MDMs infected with Hu6 showed a down regulatory pattern of IL-10 and TNFα compared to stimulations by S7565. Cells stimulated with B1018 and Hu6 had low levels of matrix metalloprotease-3 (MMP3) and high levels of tissue inhibitor of metalloprotease-1 (TIMP1) at 96-hr PI relative to MDMs stimulated by S7565.

Conclusion:

Taken together, results suggest that the bovine (B1018) and the human (Hu6) MAP isolates lead to anti-inflammatory and anti-invasive pathways in the macrophage environment whereas the sheep (S7565) MAP isolate induces a pro-inflammatory pathway. Thus the infecting strain genotype may play a role in polarizing the host immune responses and dictate the clinicopathological outcomes in this economically important disease.

PloS one3区 · 综合性期刊

A Systematic Analysis of Eluted Fraction of Plasma Post Immunoaffinity Depletion: Implications in Biomarker Discovery

3区 · 综合性期刊

ArticleOA

作者: Ruby Priyadarshini ; Debasis Dash ; Dhirendra Kumar ; Amit Kumar Yadav ; Shantanu Sengupta ; Gourav Bhardwaj ; Shadab Ahmad ; Trayambak Basak ; Ashish Kumar Singh

Plasma is the most easily accessible source for biomarker discovery in clinical proteomics. However, identifying potential biomarkers from plasma is a challenge given the large dynamic range of proteins. The potential biomarkers in plasma are generally present at very low abundance levels and hence identification of these low abundance proteins necessitates the depletion of highly abundant proteins. Sample pre-fractionation using immuno-depletion of high abundance proteins using multi-affinity removal system (MARS) has been a popular method to deplete multiple high abundance proteins. However, depletion of these abundant proteins can result in concomitant removal of low abundant proteins. Although there are some reports suggesting the removal of non-targeted proteins, the predominant view is that number of such proteins is small. In this study, we identified proteins that are removed along with the targeted high abundant proteins. Three plasma samples were depleted using each of the three MARS (Hu-6, Hu-14 and Proteoprep 20) cartridges. The affinity bound fractions were subjected to gelC-MS using an LTQ-Orbitrap instrument. Using four database search algorithms including MassWiz (developed in house), we selected the peptides identified at <1% FDR. Peptides identified by at least two algorithms were selected for protein identification. After this rigorous bioinformatics analysis, we identified 101 proteins with high confidence. Thus, we believe that for biomarker discovery and proper quantitation of proteins, it might be better to study both bound and depleted fractions from any MARS depleted plasma sample.

项与 HU-6 相关的新闻（医药）

2025-01-08

·PRNewswire

Rivus Pharmaceuticals to Present Corporate Update at 2025 J.P. Morgan Healthcare Conference

– Topline data readout from Phase 2 M-ACCEL study planned for Q2 2025 – CHARLOTTESVILLE, Va. and SAN FRANCISCO, Jan. 8, 2025 /PRNewswire/ -- Rivus Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company dedicated to treating cardiometabolic diseases driven by obesity, today announced that Jayson Dallas, M.D., chief executive officer, will provide a corporate update during a presentation at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco. The corporate presentation will highlight Rivus' new class of investigational therapies, called Controlled Metabolic Accelerators (CMAs), and will include updates on the clinical development of its lead program, HU6, and preclinical pipeline progress. HU6 is a once-daily, oral investigational medicine that promotes sustained body fat loss while preserving muscle mass by increasing resting metabolic rate in a controlled manner. The company has completed the active six-month dosing phase of M-ACCEL, a Phase 2 study in 220 patients with metabolic dysfunction associated steatohepatitis (MASH), with topline data expected in the second quarter of 2025. M-ACCEL will be the third Phase 2 study of HU6 to be completed. "Obesity is at the root of chronic diseases that kill more people every year than all cancers combined. We believe that HU6 and our portfolio of CMAs can potentially be important and transformative therapies for patients with diseases driven by obesity while preserving lean body mass," said Dr. Dallas. "We now have clinical experience with HU6 in more than 400 patients, across different patient populations." J.P. Morgan Healthcare Conference Presentation Details Rivus Pharmaceuticals will present in the private company track at the 43rd Annual J.P. Morgan Healthcare Conference on Monday, January 13, at 8:30 a.m. Pacific Time (11:30 a.m. Eastern Time) at the Westin St. Francis Hotel. About Controlled Metabolic Accelerators (CMAs) Rivus is advancing a new class of investigational therapies called Controlled Metabolic Accelerators (CMAs) that have the potential to improve metabolic health for people with obesity and associated metabolic diseases. Rivus' CMAs are oral small molecules in development to increase resting metabolic rate, which results in increased consumption of energy, primarily from fat. The loss in fat mass may address multiple cardiometabolic conditions driven by adiposity. CMAs increase metabolism in a manner that is consistent and imperceptible to the patient by leveraging the natural metabolic process of mitochondrial uncoupling. In preclinical studies, mitochondrial uncoupling was shown to account for a significant portion (20% to 50%) of daily energy expenditure. Caloric-restriction strategies, on the other hand, reduce energy input and result in loss of muscle mass as well as fat. Initial data in humans has demonstrated that CMAs provided fat-selective weight loss, improved insulin sensitivity, and significantly reduced oxidative stress and inflammation. About HU6 HU6, a novel, oral, once-daily investigational therapy, is Rivus' lead CMA. It is a purposely designed investigational oral small molecule that is intended to be a foundational monotherapy for cardiac, liver, diabetes and obesity indications. HU6 has been demonstrated to promote sustained body fat loss by imperceptibly increasing resting metabolism, which results in fat burn, while preserving muscle mass. The current clinical development of HU6 is focused on metabolic diseases with the most morbidity and greatest treatment needs: obesity-related heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatohepatitis (MASH)/metabolic dysfunction-associated steatotic liver disease (MASLD). To date, more than 400 patients have been treated with HU6 as part of the clinical development program. Results of a Phase 2 metabolic study in patients with a high body mass index (BMI) and MASLD showed that once-daily HU6 significantly reduced liver fat content and body weight with no loss of lean muscle mass and improved key markers of systemic inflammation and metabolism.1 HU6 was well tolerated in this trial; side effects were mainly mild or moderate in severity. Results from the Phase 2a HuMAIN study (ClinicalTrials.gov: NCT05284617) of HU6 in patients with obesity-related HFpEF showed the trial met its primary endpoint, demonstrating that treatment with HU6 resulted in statistically significant weight loss. The rationale for the use of HU6 in HFpEF and the design of the HuMAIN trial were published in the European Journal of Heart Failure in June 2024.2 The company is currently evaluating HU6 in the randomized, double-blind, placebo-controlled, parallel-group Phase 2 M-ACCEL trial (ClinicalTrials.gov: NCT05979779) in patients with MASH. The primary endpoint is percent change from baseline in liver fat as assessed by magnetic resonance imaging liver proton density fat fraction (MRI-Liver PDFF) at six months. The study is being conducted at approximately 20 clinical sites in the United States. About Rivus Pharmaceuticals Rivus Pharmaceuticals, Inc., a leader in mitochondrial biology, is dedicated to improving metabolic health by advancing a new class of investigational therapies called Controlled Metabolic Accelerators (CMAs). Rivus' lead CMA is the investigational small molecule HU6 in clinical development to treat obesity-related heart failure with preserved ejection fraction (HFpEF), metabolic dysfunction associated steatohepatitis (MASH)/metabolic dysfunction-associated steatotic liver disease (MASLD) and Type 2 diabetes. For more information, please visit . Media Contact: Nicole Raisch Goelz Real Chemistry [email protected] (408) 568-4292 References Noureddin M, Khan S, Portell F, et al. Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled phase 2a trial. Lancet Gastroenterol Hepatol. 2023;8(12):1094-1105. Kitzman DW, Lewis GD, Pandey A, et al. A novel controlled metabolic accelerator for the treatment of obesity-related heart failure with preserved ejection fraction: Rationale and design of the Phase 2a HuMAIN trial. Eur J Heart Fail. June 26, 2024. SOURCE Rivus Pharmaceuticals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期临床结果

2024-11-06

·CPHI制药在线

MASH | 脂肪肝药物争霸谁将胜出?

关注并星标CPHI制药在线 2024年医药开发领域的一件里程碑事件当属Madrigal Pharmaceuticals的MASH（代谢功能障碍相关脂肪性肝炎）药物Rezdiffra获得FDA的加速批准，成为了FDA认可的首款MASH药物。这标志着长期以来在MASH治疗领域的首次重大突破。此前，许多临床试验在MASH领域都壮志难酬，因此Rezdiffra的问世具有划时代意义。有分析师预测，Rezdiffra的销售额到2030年将超过30亿美元，并且具有达到60至74亿美元峰值销售的潜力。 1.Rezdiffra破壁之后的MASH 然而Rezdiffra的上市对于MASH来说远未达到“眼前有景道不得，崔颢题诗在上头”的影响。相反的是，MASH赛道上如今更是一派人喊马嘶、奋勇争先的场景。造成这种局面的根本原因，在于MASH领域仍然存在着严重的未满足情况，而且这背后是一个非常庞大的市场。MASH的整体市场规模到2030年将增长到目前的三倍多，达到95亿美元以上的水准。 Rezdiffra的获批对于MASH这个庞大的患者群体来说只是杯水车薪，况且Rezdiffra本身也是通过加速批准上市的，针对的是非肝硬化MASH的患者群体，还需要进行上市后验证性的III期研究来确定其治疗效果并获得FDA的全面批准。Madrigal最近完成了III期代偿性MASH研究MAESTRO-NASH OUTCOMES的招募计划，针对845名伴有代偿性MASH肝硬化且具有三种代谢风险因素的患者。受试者以3:1的比例被随机分配，每天口服80mg的Rezdiffra或安慰剂。该试验的主要终点是与肝功能相关的复合事件发生率。试验的持续时间预计为两到三年，目的是收集足够数量的临床结果事件。MAESTRO-NASH OUTCOMES是Madrigal评估Rezdiffra疗效的几项III期临床试验之一。其他试验还包括针对中度至重度肝纤维化的MAESTRO-NASH试验和MAESTRO-NAFLD-1试验。如果试验结果积极，可能会支持Rezdiffra用于治疗非肝硬化NASH的全面批准。 2.Rezdiffra的市场准入与挑战 Rezdiffra的推出受到了医学界和金融分析师的热烈欢迎。目前的处方数据显示，约30%的F2/F3 MASH（中重度纤维化MASH）患者在药物上市几个月内已开始使用Rezdiffra。这一吸收率与2022年上市的tirzepatide相当，因此可被视为非常不错。分析师预计，Rezdiffra的峰值销售额可能达到60亿至74亿美元，目标为美国5%的F2/F3 MASH患者群体。如同所有药物一样，Rezdiffra的市场表现受到医疗保险覆盖的直接影响。对Rezdiffra有利的是，尽管它目前的身份还是加速批准产品，但报销前景似乎正在改善，包括Cigna和United Healthcare在内主要保险公司已为其制定了较为宽松的预先授权要求。Madrigal的目标是到2024年底覆盖80%的商业保险人群。Rezdiffra已经获得了Medicaid的覆盖，预计将在2025年1月获得Medicare的覆盖。而且目前已经有许多Medicare受益人通过根据医疗例外程序获得了Rezdiffra处方。作为Madrigal的“处子产品”，Rezdiffra的销售情况将直接决定Madrigal的命运。公司在2023年未产生任何首收入，预计2025年将实现3.55亿美元的进项。对于2024财年，8700万美元将是一个能令管理层感到满意的业绩。Madrigal的强大现金储备为11亿美元，预计可以完全支持Rezdiffra的全面上市，这将为有效的商业运营提供坚实基础。根据Madrigal最新公布的2024年第三季度公司财报来看，Rezdiffra取得了令人信息的销售业绩。Rezdiffra的销售额达到6220万美元，不仅远超第二季度的1460万美元业绩，也远远超出市场预期。分析显示Rezdiffra有可能成为MASH领域的标准治疗手段。从真实世界的数据中可以看出，Rezdiffra正稳步成为NASH患者中度至重度肝纤维化的基础疗法。在进行验证性研究的基础之上，Madrigal还在只争朝夕地利用目前独领风骚的天赐良机，积极扩大Rezdiffra的标签范围，他们尤其关注向 F4 （肝硬化）患者群体的潜在扩展，这可能使Rezdiffra的市场机会翻倍。Madrigal还期待EASL-EAD-EASO（欧洲肝脏研究协会-欧洲肝病学会-欧洲肥胖学会）更新治疗指南，预计将推荐Rezdiffra用于MASH治疗。“法统”地位的认定将显著影响处方模式，进一步巩固Rezdiffra在市场中的地位。 3.GLP-1后浪将至然而Rezdiffra先发的成就并不能保证他们的“既寿永昌”。在MASH和相关领域，Rezdiffra将遭遇期待“后发先至”的竞争者们的强力挑战，尤其是以tirzepatide和semaglutide为代表的GLP-1药物。后者的优势不仅在于他们已经在肥胖症和T2D等代谢疾病领域取得了无以伦比的成就，也因为其拥有者都是当今制药行业的巨头，拥有充足的开发资金和海量的商业化经验。肥胖症的治疗对于MASH的进步产生了推波助澜的作用。Semaglutide和tirzepatide都起家于T2D并扩军至肥胖症，但MASH也是诺和与礼来心心念念的重要战场。脂肪肝在超重和肥胖人群中的比例分别超过了75%和90%，减轻体重可能会降低患者进展为MASH的风险。Semaglutide和tirzepatide都在针对MASH进行临床研究。Semaglutide在改善肝纤维化方面面临挑战，因为之前的IIb期试验未能实现这一终点。但一项最新的为期72周的III期研究结果显示，37%的Wegovy使用者得到了肝脏疤痕或纤维化的改善，且疾病没有恶化，而安慰剂队列的比例为23%。这项数据有望为semaglutide标签最终扩展到MASH提供重要背书。除此之外，63%的Wegovy使用者还得到了症状缓解，且纤维化没有恶化，而安慰剂队列的数据为34%。过去开发的MASH药物都是念兹在兹地专门针对肝脏开发，但随着GLP-1药物越来越明显地表现出跨领域治疗能力，其针对MASH的开发前景也逐渐明朗起来。不过很多医生并不认为GLP-1药物会完全取代肝脏导向治疗。有些人认为，肥胖药物可能对早期MASH患者（没有严重纤维化的患者）更有帮助，而肝脏导向的疗法对严重纤维化和肝硬化患者可能更有益。Wegovy此前的II期研究的确没有能够实现改善纤维化这一终点，因为纤维化的逆转对预防肝硬化和严重后果（如癌症或肝脏移植）至关重要。尽管如此，诺和诺德对Wegovy的这个新结果仍然感到鼓舞，并表示预计将在明年上半年向美国和欧洲申请监管批准。相关的临床试验仍正在进行中，测试Wegovy是否降低四年以上与肝脏相关的临床结果的风险，这些数据预计将在2029年公布。考虑到semaglutide在此前改善纤维化未能达到终点的事实，诺和诺德可能会把将进军MASH更大市场的希望寄托在了他们颇为看重的管线资产CagriSema之上。礼来在今年6月的欧洲肝脏研究协会肝脏大会（EASL）上公布了II期临床试验，显示了他们的tirzepatide能够显著改善MASH纤维化的效果，令业界非常期待。BI和Zealand Pharma的GLP-1/胰高血糖素双受体共激动剂survodutide在EASL 2024会议展示的MASH结果同样令人印象深刻，预计也将成为MASH领域重要的参与者。 4.MASH中后期候选药物管线全景 Rezdiffra在临床试验中，在改善肝纤维化和解决MASH方面达到了主要终点。特别是在MAESTRO-NASH和MAESTRO-NAFLD-1试验中，Rezdiffra显示出对肝脂肪减少、纤维化改善和NASH解决的显著效果。第 3 阶段数据显示，80% 的患者的纤维化得到改善或稳定。尽管总体耐受性良好，但在治疗初期，部分患者可能会经历胃肠道不良事件，如腹泻和恶心。表1. 部分MASH中后期管线产品 MASH管线中存在至少六款人类成纤维细胞生长因子 21 (FGF-21) 类似物的药物候选物。FGF-21 是一种由肝脏分泌的代谢相关激素。在改善代谢紊乱方面具有显著效果，包括调节脂质代谢、减少肝脏脂肪变性、炎症和纤维化等。在增加胰岛素敏感性、减少炎症、改善脂质代谢、调节葡萄糖代谢、抗炎和抗纤维化作用，以及保护肝细胞免遭受过度和不足饮食压力的影响方面具有积极用作用。 89Bio 的 pegozafermin 是一种长效 FGF-21 类似物，正在进行两项全球 3 期 MASH 试验。2b 阶段的数据很有希望，达到了两个主要终点，即纤维化至少改善 1 个阶段，MASH 指标改善且纤维化没有恶化。Evaluate预测pegozafermin 2027 年上市，2030年销售额将达到 6.5 亿美元以上。 Akero Therapeutics 的 3 期资产efruxifermin（由安进公司授权）也是FGF-21 类似物。一些分析师认为，Akero 和 89Bio 的纤维化数据比 Rezdiffra 和 tirzepatide 的数据更强。法国Inventiva 的3期 lanifibranor 可激活 PPAR（过氧化物酶体增殖激活受体）的三种亚型，可能提供抗纤维化、抗炎和有益的代谢作用（PPAR-alpha 和 PPAR-gamma 激动剂已用于治疗糖尿病和胆固醇相关疾病）。Lanifibranor的顶线结果预计将在 2025 年底公布。Evaluate 预测其2030 年的销售额将超过 9 亿美元。 Galectin Therapeutics 的MASH资产 belapectin 是galectin-3抑制剂，galectin-3蛋白在许多生物过程（如细胞增殖、炎症和凋亡）中发挥重要作用，特别与纤维化和慢性疾病密切相关。因此，Galectin-3抑制剂具有治疗心力衰竭、癌症和MASH的潜力。Belapectin正在进行 2b/3 期试验，针对MASH 相关肝硬化中的食管静脉曲张。 Sagimet Biosciences 的口服小分子药物denifanstat 是MASH临床管线中唯一的一款脂肪酸合酶 (FASN) 抑制剂，机制针对脂肪堆积、炎症和纤维化起效。2024 年 6 月公布了不错的 2b 期数据，随后于10月份获得了FDA突破性疗法的认定，并将于今年开始3期临床研究。 Rivus Pharmaceuticals的HU6是一种创新的小分子药物，属于受控代谢加速器（Controlled Metabolic Accelerators, CMA）类别，通过加速脂肪代谢来治疗多种心血管和代谢疾病，包括2型糖尿病、肥胖相关心力衰竭和MASH。HU6通过促进脂肪的分解而不是减少热量的摄入来驱动体重减轻，目前正在进行一项针对MASH的2a试验，数据显示肝脏脂肪、体重以及炎症和代谢标志物显著减少。对于像 MASH 和肥胖症这样复杂、多因素疾病，最有效的解决方案可能是结合多种机制。改善纤维化的数据是FDA最希望看到的，因此组合疗法将在未来MASH疗法开发中占据重要地位。GLP-1药物与更多肝脏药物（例如resmetirom 和 FGF-21 激动剂）组成的联合疗法将越来越多地出现在MASH管线中。FGF-21 激动剂与甲状腺受体激动剂的联合疗法也是有可能占据MASH的一席之地。 5.总结与展望 MASH的药物开发前景充满机遇与挑战。在疾病管理方面，由于MASH的发病机制复杂，通常涉及代谢紊乱、胰岛素抵抗、炎症及纤维化，因此开发针对多重靶点的药物成为一大趋势。例如GLP-1受体激动剂、PPAR受体调节剂以及FGF21类似物在临床前和早期临床试验中表现出潜力。这些药物通过调节代谢途径，降低肝脏脂肪积聚并减少炎症反应，为未来的治疗提供了希望。在市场准入方面，MASH的治疗药物面临较高的开发和审批门槛。其临床试验设计复杂，尤其是因为MASH早期诊断困难且进展缓慢，需要长期随访才能评估药物的有效性。尽管如此，随着肥胖和2型糖尿病患者的增加，全球范围内的MASH患者数量急剧上升，推动了药物研发和商业化的迫切需求。医疗系统和支付方对MASH药物的可支付性、疗效和安全性提出了更高的要求，未来成功的市场准入可能取决于药物的长期临床益处和成本效益分析。如何克服临床开发的复杂性并满足市场准入要求，将决定这些新药在未来的成功与否。 Ref. MASH Up? Liver disease could be the next big market. Madrigal Pharmaceuticals enrols patients in Phase III trial of NASH cirrhosis drug. Clinical Trials Arena. 22. 10. 2024. GLP-1 therapies: a new frontier in MASH treatment. Clinical Trials Arena. 28. 08. 2024. Sagimet Receives FDA Breakthrough Therapy Designation for Denifanstat in MASH. Sagimet Press Release. 01. 10. 2024. Belapectin: Targeting Galectin-3. Galectin Therapeutics Press Release. Retrieved on 26. 10. 2024. Madrigal Pharmaceuticals' SWOT analysis: rezdiffra launch fuels stock's potential. Investing.com. 24. 10. 2024. Haas, J. Madrigal Shatters Street Expectations With $62m In Q3 Rezdiffra Sales. Scrip. 31. 10. 2024. END 【智药研习社线上研习会报名】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床3期上市批准加速审批临床结果申请上市

2024-09-30

·FierceBiotech

Rivus reveals data to back up muscle-sparing claims of phase 2 obesity drug

HU6 is known as a controlled metabolic accelerator, a new class of therapies that Rivus hopes can “promote sustained body fat loss while preserving muscle mass.” Rivus Pharmaceuticals has unveiled the data behind its phase 2 obesity win in heart failure patients, showing that the candidate can indeed help patients reduce weight while they retain muscle.The asset, dubbed HU6, is designed to boost the breakdown of fat by stopping it from accumulating, rather than by reducing calory intake. The mechanism could help patients lose fat tissue while preserving muscle—the goal of many next-gen obesity drugs.Sparing muscle is particularly important for heart failure patients, who may already be frail and lack skeletal muscle mass. The HuMAIN study specifically recruited patients with obesity-related heart failure with preserved ejection fraction.Rivus already announced in August that the trial hit its key endpoint, but today fleshed out that win with some figures. Specifically, patients who ended on the highest, 450 mg, daily dose of HU6 lost an average of 6.8 pounds after three months, which was 6.3 pounds more than lost among the placebo group.When it came to visceral fat—a term for fat that collects around the internal organs in the abdomen—this was reduced by 1.5% from baseline. What’s more, there was “no significant reduction in lean body mass with HU6 from baseline or compared with placebo,” said the company, keeping alive hopes that the drug can indeed help patients lose the right type of weight.Elsewhere, HU6 was tied to reductions in systolic and diastolic blood pressure from baseline of 8.8 mmHg and 4.1 mmHg, respectively. These reductions weren’t linked to an increase in heart rate, the biotech noted. The 66 patients enrolled in the study were mainly elderly and obese, with multiple comorbidities and taking an average of 15 other medicines. The most common treatment-emergent adverse events were diarrhea, COVID-19 and shortness of breath, with most of these events being mild to moderate in severity. There were no treatment-related serious adverse events.HU6 is known as a controlled metabolic accelerator (CMA), a new class of therapies that Rivus hopes can “promote sustained body fat loss while preserving muscle mass.”“With these new clinical data, which highly correlate to the results from our phase 2 study in [metabolic dysfunction-associated steatotic liver disease], we have now observed in different populations that HU6, a novel CMA, reduced fat mass and preserved lean body mass, which is especially beneficial in patients with HFpEF,” Rivus CEO Jayson Dallas, M.D., said in a statement.“The positive HuMAIN results support the potential differentiating profile of HU6 in HFpEF, which could be the first disease-modifying treatment for this debilitating syndrome,” Dallas added. “The findings also support advancing our HFpEF clinical program with HU6.”Roche is one high-profile entrant in the obesity space that has its own solution to retaining muscle. The Swiss pharma hopes that combining an injectable dual GLP-1/GIP receptor agonist acquired with Carmot alongside its own anti-myostatin antibody could also help patients reduce the muscle loss typically associated with losing weight.

临床2期临床结果

100 项与 HU-6 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床2期	美国	Rivus Pharmaceuticals, Inc.	2023-11-17
肥胖	临床2期	美国	Rivus Pharmaceuticals, Inc.	2023-11-17
射血分数保留型心力衰竭	临床2期	美国	Rivus Pharmaceuticals, Inc.	2022-10-30
非酒精性脂肪性肝炎	临床2期	美国	Rivus Pharmaceuticals, Inc.	2021-04-19

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05284617 (HuMAIN, PRNewswire) 人工标引	临床2期	心脏衰竭	66	HU6	餘蓋壓願鬱簾鏇簾願遞(壓膚製窪膚網夢齋獵構) = 鏇淵製廠繭蓋廠鹹鏇選鏇餘築網艱鹽鑰鑰觸廠 (顧積鑰憲鏇艱製遞製網 ) 更多	积极	2025-03-12
				Placebo	餘蓋壓願鬱簾鏇簾願遞(壓膚製窪膚網夢齋獵構) = 窪築糧獵選壓遞壓廠獵鏇餘築網艱鹽鑰鑰觸廠 (顧積鑰憲鏇艱製遞製網 ) 更多
NCT05284617 (HuMAIN, PRNewswire \| NEWS) 人工标引	临床2期	射血分数保留型心力衰竭	66	HU6	鬱夢淵簾鑰鹹糧鑰淵衊(選簾憲願廠淵艱夢醖醖) = In addition to meeting the primary endpoint, the HuMAIN study met several secondary efficacy and pharmacodynamic endpoints. 鑰鑰膚齋鏇範餘齋鏇憲 (製簾齋繭齋鑰齋醖積膚 ) 达到更多	积极	2024-08-13
				Placebo