A Phase 2a Open-label Study of the Oral Farnesoid X Receptor (FXR) Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B (CHB) Patients in Combination With Pegylated Interferon alpha2a (Peg-IFN) Alone and With Entecavir (ETV)

This is a multi centre, two parallel arm, randomized, open-label, Phase 2a experimental study of oral Farnesoid X Receptor (FXR) modulator EYP001a to assess its safety and anti-viral effect when administered to non-treated (treatment naive or off treatment) chronic Hepatitis B (CHB) patients in combination with entecavir (ETV) and pegylated interferon alpha2a (peg-IFN). An experimental treatment period of 16 weeks will be followed by a 24 week maintenance period with ETV standard of care (SoC).

开始日期2020-05-25

申办/合作机构

ENYO Pharma SA初创企业

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100 项与 Vonafexor 相关的转化医学

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100 项与 Vonafexor 相关的专利（医药）

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项与 Vonafexor 相关的文献（医药）

2023-03-01·Journal of hepatology

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH

Article

作者: Darteil, Raphaël ; Harrison, Stephen A ; Lawitz, Eric ; Alkhouri, Naim ; Francque, Sven ; Bureau, Christophe ; Vonderscher, Jacky ; Sanyal, Arun ; Scalfaro, Pietro ; Abdelmalek, Manal ; Wolf, Myles ; Loustaud-Ratti, Véronique ; Girma, Hugo ; Couchoux, Harold ; Ratziu, Vlad

BACKGROUND & AIMS:

The LIVIFY trial investigated the safety, tolerability, and efficacy of vonafexor, a second-generation, non-bile acid farnesoid X receptor agonist in patients with suspected fibrotic non-alcoholic steatohepatitis (NASH).

METHODS:

This double-blind phase IIa study was conducted in two parts. Patients were randomised (1:1:1:1) to receive placebo, vonafexor 100 mg twice daily (VONA-100BID), vonafexor 200 mg once daily (VONA-200QD), or 400 mg vonafexor QD (VONA-400QD) in Part A (safety run-in, pharmacokinetics/pharmacodynamics) or placebo, vonafexor 100 mg QD (VONA-100QD), or VONA-200QD (1:1:1) in Part B. The primary efficacy endpoint was a reduction in liver fat content (LFC) by MRI-proton density fat fraction, while secondary endpoints included reduced corrected T1 values and liver enzymes, from baseline to Week 12.

RESULTS:

One hundred and twenty patients were randomised (Part A, n = 24; Part B, n = 96). In Part B, there was a significant reduction in least-square mean (SE) absolute change in LFC from baseline to Week 12 for VONA-100QD (-6.3% [0.9]) and VONA-200QD (-5.4% [0.9]), vs. placebo (-2.3% [0.9], p = 0.002 and 0.012, respectively). A >30% relative LFC reduction was achieved by 50.0% and 39.3% of patients in the VONA-100QD and VONA-200QD arms, respectively, but only in 12.5% in the placebo arm. Reductions in body weight, liver enzymes, and corrected T1 were also observed with vonafexor. Creatinine-based glomerular filtration rate improved in the active arms but not the placebo arm. Mild to moderate generalised pruritus was reported in 6.3%, 9.7%, and 18.2% of participants in the placebo, VONA-100QD, and VONA-200QD arms, respectively.

CONCLUSIONS:

In patients with suspected fibrotic NASH, vonafexor was safe and induced potent liver fat reduction, improvement in liver enzymes, weight loss, and a possible renal benefit.

CLINICAL TRIAL NUMBER (EUDRACT):

2018-003119-22.

CLINICALTRIALS:

GOV IDENTIFIER:

NCT03812029.

IMPACT AND IMPLICATIONS:

Non-alcoholic steatohepatitis (NASH) has become a leading cause of chronic liver disease worldwide. Affected patients are also at higher risk of developing chronic kidney disease. There are no approved therapies and only few options to treat this population. The phase IIa LIVIFY trial results show that single daily administration of oral vonafexor, an FXR agonist, leads in the short term to a reduction in liver fat, liver enzymes, fibrosis biomarkers, body weight and abdominal circumference, and a possible improvement in kidney function, while possible mild moderate pruritus (a peripheral FXR class effect) and an LDL-cholesterol increase are manageable with lower doses and statins. These results support exploration in longer and larger trials, with the aim of addressing the unmet medical need in NASH.

2023-03-01·Biochemical pharmacology

Pharmacological characterization of second generation FXR agonists as effective EphA2 antagonists: A successful application of target hopping approach

Article

作者: Giorgio, Carmine ; Lodola, Alessio ; Galvani, Francesca ; Zappia, Alfonso ; Mor, Marco ; Ballabeni, Vigilio ; Barocelli, Elisabetta ; Bertoni, Simona ; Scalvini, Laura ; Tognolini, Massimiliano ; Ferrari, Francesca Romana

It is well demonstrated the key role of Eph-ephrin system, specifically of EphA2 receptor, in supporting tumor growth, invasion, metastasis and neovascularization. We previously identified FXR agonists as eligible antagonists of Eph-ephrin system. Herein we characterize new commercially available FXR (Farnesoid X Receptor) agonists as potential Eph ligands including Cilofexor, Nidufexor, Tropifexor, Turofexorate isopropyl and Vonafexor. Our exploration based on molecular modelling investigations and binding assays shows that Cilofexor binds specifically and reversibly to EphA2 receptor with a Ki value in the low micromolar range. Furthermore, Cilofexor interferes with the phosphorylation of EphA2 and the cell retraction and rounding in PC3 prostate cancer cells, both events depending on EphA2 activation. In conclusion, we can confirm that target hopping can be a successful approach to discover new moiety of protein-protein inhibitors.

2021-12-01·Journal of viral hepatitis2区 · 医学

Farnesoid X receptor agonist for the treatment of chronic hepatitis B: A safety study

2区 · 医学

Article

作者: Roy, Elise ; Kootstra, Neeltje ; Tangkijvanich, Pisit ; Radreau‐Pierini, Pauline ; Darteil, Raphael ; Scalfaro, Pietro ; Andre, Patrice ; Reesink, Henk ; Vonderscher, Jacky ; Erken, Robin ; Barzic, Noelie ; Flisiak, Robert ; Laveille, Christian ; Girma, Hugo

Abstract:

The nuclear farnesoid X receptor (FXR) regulates bile acid homeostasis and is a drug target for metabolic liver diseases. FXR also plays an important role in hepatitis B virus (HBV) DNA transcription. In vitro and in mice, FXR agonist treatment leads to inhibition of viral replication and a decline in viral proteins, pregenomic RNA (pgRNA) and HBV DNA levels. We aimed to translate this to a clinical use by primarily evaluating the safety and secondary the anti‐viral effect of Vonafexor, a FXR agonist, in chronic hepatitis B (CHB) patients. In total, 73 CHB patients were enrolled in a two‐part Phase Ib double‐blind, placebo‐controlled trial. Patients were randomized to receive oral Vonafexor (100, 200 and 400 mg once daily, or 200 mg twice daily), placebo, or entecavir (Part A, n = 48) or to receive Vonafexor (300 mg once daily or 150 mg twice daily), or placebo, combined with pegylated‐interferon‐α2a (Part B, n = 25) for 29 days. Patients were followed up for 35 days. Enrolled CHB patients were mostly HBeAg‐negative. Vonafexor was overall well tolerated and safe. The most frequent adverse events were moderate gastrointestinal events. Pruritus was more frequent with twice‐daily compared with once‐daily regimens (56%–67% vs. 16%, respectively, p < 0.05). Vonafexor monotherapy of 400 mg once daily decreased HBsAg concentrations (–0.1 log10 IU/mL, p < 0.05), and Vonafexor/pegylated‐IFN‐α2a combination therapy decreased HBcrAg and pgRNA. In conclusion, Vonafexor was safe with a decline in HBV markers observed in CHB patients suggesting a potential anti‐viral effect the therapeutic potential of which has to be evaluated in larger trials.

项与 Vonafexor 相关的新闻（医药）

2024-01-21

·同写意

十年面壁图破壁，非酒精性脂肪性肝炎历史性突破的前夕

写意精品课 | 方法与工具—快速打造生物药供应链企业的独特品牌价值，欢迎报名！1从非酒精性脂肪性肝炎更名说起作为一种尚未有FDA疗法获批的适应症，非酒精性脂肪性肝炎领域最近酝酿着变化。首先是NASH的易名，从非酒精性脂肪性肝炎（Nonalcoholic Steatohepatitis）更改为代谢功能障碍相关脂肪性肝炎（MASH，Metabolic dysfunction-associated steatohepatitis）。其实这个更名在去年夏天就已经发生了，这是根据德尔菲共识命名法（Delphi Consensus Nomenclature）做出的，目的是呼吁人们认识到精确疗法和以患者为中心的护理在治疗MASH中的重要性。2020年，全球肝脏协会和患者权益团体召集了一个小组，审查脂肪肝疾病各阶段的命名和定义选项。2023年夏天采用的名称强调了肝脏疾病的代谢基础，使其与肥胖或糖尿病等根本原因更加紧密地联系在一起。随着研究的进展，尤其是GLP-1糖尿病药物在肥胖症领域取得的突破，大多数被归类为非酒精性脂肪性肝病的疾病与肥胖、胰岛素抵抗、高胆固醇或高血脂等代谢因素产生了关联。全球肝脏协会建议更名的原因之一，是通过删除“脂肪”和“酒精”的表述来减少耻辱（NASH本身并不含有fatty描述，但NFALD中包含，见下文）。但实际上，有些患者似乎更喜欢“非酒精性”的定语，这样可以向家人传达一个信息：酒精不是他们肝病的罪魁祸首，他们就不会对自己的饮酒习惯感到愧疚（当然这个逻辑是完全错误的）。•　脂肪肝病 (SLD，Steatotic liver disease)：涵盖脂肪变性的肝病总体术语。•　代谢功能障碍相关脂肪肝病（MASLD，metabolic dysfunction-associated steatotic liver disease）：对应以前的非酒精性脂肪肝病（NAFLD，Nonalcoholic fatty liver disease），包括患有肝脂肪变性并且至少具有五种心脏代谢危险因素之一的疾病。•　MetALD：新类别疾病，针对患有MASLD并且每周饮酒量超过140克的女性，以及每周饮酒量超过超过210克男性。•　代谢功能障碍相关脂肪性肝炎（MASH，Metabolic dysfunction-associated steatohepatitis）：取代类此前的“非酒精性脂肪性肝炎”（NASH，Nonalcoholic Steatohepatitis），指一种严重的脂肪肝疾病，由于肝脏中的脂肪沉积，导致肝脏肿胀并受损。MASH是一种晚期形式的脂肪肝，其特征是器官炎症，主要由肥胖引起，2 型糖尿病也是已知的危险因素。这种疾病很难诊断，被称为“沉默的疾病”，因为 MASH 几乎没有任何症状，直到发展到后期，这可能会对肝脏造成更严重的损害和疤痕。•　隐源性 SLD（Cryptogenic SLD）：专指脂肪肝病症的术语，其致病因素仍然难以捉摸，特别是在不存在代谢危险因素的情况下。2MASH疗法巨大的未满足度MASH的特殊性，在于它直到今天仍然没有一款获得FDA批准的疗法。其巨大的未满足需求营造出“十年面壁图破壁”的紧迫感。预计从2022年到2032年的十年间，七个主要市场（7MM，美国、法国、德国、意大利、西班牙、英国和日本）的MASH确诊病例数将增长450万例，从2022年的2204万人增加到2032 年的2655万人。美国将成为最大市场，预测美国到2032年将有1045万确诊病例。MASH在日本和英国增长最快，预计2032年这两个国家的确诊病例将在2022至2032的十年间分别增长32%和71%。美国的同期增长率将为12%。MASH疗法的开发相当艰巨，自从Intercept Pharmaceuticals的二期MASH数据让投资者陷入疯狂以来，已经过去近10年了。当时的数据曾经推动其股价上涨超过500%，但这一切的雕栏玉砌最终却成为了一场黄粱美梦。FDA在去年6月份（第二次）拒绝了Intercept Pharmaceuticals的法尼醇X受体激动剂奥贝胆酸（obeticholic acid，商品名Ocaliva）片剂用于治疗非酒精性脂肪性肝炎导致的肝硬化前期肝纤维化患者。曾被寄以厚望的Intercept在第二天就决绝地做出了放弃他们的所有MASH项目，并且解雇三分之一员工的决定。Intercept表示，将放弃对MASH的执念，转向奥贝胆酸与bezafibrate的联合疗法针对原发性胆汁性胆管炎的开发。Intercept只是MASH光环下的一个缩影，自从MASH适应症吸引制药商投入研发的黄金时代以来，许多试图治疗MASH的制药公司前赴后继，但始终未能攻克这个艰巨的阵地。之前的领跑者Intercept和Genfit已经选择激流勇退。阿斯利康也从其2期产品线中清除了GLP-1/Glucagon双受体共激动剂cotadutide。该产品于2022年进入MASH试验，但因无法招募足够的患者而停止。辉瑞也在 2021年放弃了其2期MASH候选药物。然而在巨大利润的吸引下，大量后来者迎难而上，其中包括Madrigal，Akero Therapeutics、勃林格殷格翰、礼来和辉瑞等。3Madrigal有望开天辟地Madrigal Pharmaceuticals已经提交了他们的MASH疗法Resmetirom（图1）的NDA申请，并且获得了FDA的优先审评和突破性疗法的认定，其PDUFA日期为2024年3月14日。业内众多人士纷纷看好这款小分子药物将实现MASH疗法的历史性突破，加冕FDA批准的首款MASH药物。与奥贝胆酸法尼醇 X 受体激动剂的机制不同，Resmetirom是一款每日一次口服的甲状腺激素β受体（THR）-β选择性激动剂。甲状腺激素（Thyroid hormone）通过激活肝细胞中的 β 受体，在影响一系列健康参数的肝功能中发挥核心作用。在MASH患者中，肝脏中的甲状腺激素β活性受损，导致线粒体功能下降和脂肪酸的氧化，进而导致炎症和肝纤维化。图1. Resmetirom化学结构THR-β激动剂具有减少炎症性肝脏脂肪和纤维化的潜力，同时降低胆固醇和其他致动脉粥样硬化的脂质。Resmetirom关键的3期MAESTRO-NASH中实现了肝脏组织学改善的两个终点：NASH的缓解和肝纤维化的减少。预测显示，到2035年底，MASH治疗市场规模预计将达到483亿美元，在此期间复合年增长率为18%。2022年，MASH治疗的行业规模已超过52亿美元。如果如愿获批，resmetirom无疑将迅速成为一款重磅炸弹药物。尽管尚未获得FDA的监管审批，但临床与经济评估研究所（ICER）已经开始评估resmetirom的成本效益范围。ICER认为，resmetirom每年的价格在39600到50100美元之间是具有恰当的成本效应的。4GLP-1会后发先至吗？GLP-1已经逐渐演变成为代谢病领域内无所不能的角色，除了已获批的2型糖尿病和肥胖症之外，在MASH领域也有望取得建树。相对于小分子口服制剂的resmetirom，GLP-1多肽在业已取得了诸多安全性数据的基础上，能完成在MASH领域的后来居上吗？早在2020年，在semaglutide尚未如此光芒万丈之时，诺和诺德就已经为这款GLP-1多肽获取了NASH突破性疗法的头衔（当时的名称）。四年后，GLP-1 受体激动剂已成为MASH这个“沉默杀手” “最受认可和最受期待”的新疗法之一。诺和诺德仍在招募患有纤维化的NASH患者进行一项1200名患者的IIIa期研究，预计要到2028年才能获得数据。尽管临床试验显示了semaglutide和其他GLP-1激动剂在治疗MASH方面的潜力，但对于这些药物在肝病后期的疗效的局限性仍存在疑问。有专家认为，GLP-1激动剂在MASH的研究中“表现欠佳”。虽然血糖控制和减肥也会缓解肝脏中的脂肪浓度，但目前仍缺乏足够的数据来证明这个机制是否可以直接改善肝脏健康。尽管如此，仍有很多人认为，即使GLP-1激动剂治疗纤维化或肝硬化的效果低于预期，但这些药物仍然有巨大的市场。因为一半的 MASH 患者还患有2型糖尿病，其中约三分之二患有肥胖症，这说明如果获得批准，这些重磅药物的使用范围将会更加广泛。在一项320名患者参与的II期semaglutide研究显示，semaglutide与MASH缓解之间存在正剂量关系，但在改善纤维化方面表现不佳。MASH的缓解可能是由于患者整体代谢健康状况的改善，因此人们对GLP-1激动剂如何直接影响肝脏存在疑问。还有人明心见性地指出，肝脏中并不存在GLP-1受体。然而，GLP-1激动剂仍可能对肝脏产生有价值的间接影响。通过提高胰岛素敏感性，肝脏中的游离脂肪酸 (FFA) 应该会减少。FFA是一种能量来源，但积累过多时会导致脂肪肝。减少FFA可以缓解肝脏炎症，从而下调导致纤维化的过程。但Semaglutide只是第一代GLP-1受体激动剂疗法，它身后的一干多受体共激动剂是否会在MASH领域取得更高成就？礼来的tirzepatide是GLP1/GIP双受体共激动剂，其MASH的II期试验将在2024年读数。勃林格殷格翰与西兰制药的GLP-1/Glucagon双受体共激动剂survodutide（图2）针对MASH的关键II期数据也将与2024年上半年公布。勃林格殷格翰发言人表示，survodutide可能成为第一款减少肝脏能量摄入并增加肝脏能量消耗的抗肥胖药物。图2. Survodutide化学结构默沙东管线中也有一款MASH资产efinopegdutide，同西兰制药/勃林格殷格翰survodutide一样，也是一款GLP-1/Glucagon双受体共激动剂。Efinopegdutide已经被FDA授予快速通道资格，目前处于II期阶段。尽管肝脏中没有GLP-1受体，但却存在GIP和Glucagon受体。因此即便作为GLP-1受体激动剂的semaglutide尚未给出在MASH研究中令人信服的数据，但第二代和第三代资产（GLP-1受体共激动剂）的早期疗效数据已经显露出了相对于单纯GLP-1受体激动剂的优势。但现在下结论尚早，因为这些资产仍然出于中期研究，有些还没有组织学数据。在共激动剂中，对于不同受体的效力也存在差异。例如Efinopegdutide对GLP-1和Glucagon受体的相对效力分别约为 2:1，药物渗透肝脏也对生物学功效产生一定影响。5MASH开发现状尽管semaglutide对MASH的影响仍然有待观察，但诺和诺德对于进军MASH领域的渴望已如司马昭之心。诺和诺德正在寻求与两家生物技术初创公司合作，开发治疗心脏代谢疾病的新药。2024年1月4日，诺和诺德宣布与两家公司Omega Therapeutics和Cellarity分别签署了协议。Omega协议将重点关注治疗肥胖的新方法，而Cellarity合作伙伴关系则针对MASH药物。Cellarity利用人工智能寻找纠正细胞功能障碍的新方法，目标是开发用于MASH的小分子药物。交易的预付款、开发付款和商业里程碑付款的价值可能高达5.32亿美元。目前的MASH管线中包含不同药理学机制的候选药，主要包含以下几大类别：FXR （法尼醇 X 受体）激动剂FGF21 （成纤维细胞生长因子21）受体激动剂FGF19 类似物GLP-1受体激动剂PPAR（过氧化物酶体增殖物活化受体）调节剂甲状腺激素β受体激动剂MASH其它靶点包括G蛋白偶联受体 (GPCR)、雌激素相关受体 α (ERRα)、骨形态发生蛋白 (BMP) 和 KLF（Kruppel-like-factor）。目前处于中后期的MASH研究，除了即将撞线的resmetirom和被寄以厚望的semaglutide，survodutide之外，还包括以下候选药：•　Lanifibranor（IVA337）开发商：Inventiva Pharma阶段：III期图3. Lanifibranor化学结构Lanifibranor（图3）是新一代泛PPAR（过氧化物酶体增殖物活化受体）激动剂，用于治疗纤维化疾病，且依从性更好，是唯一处于临床开发阶段的泛PPAR激动剂，是第一种同时针对PPAR-α、PPAR-β和PPAR-γ的靶向药物。Lanifibranor被视为治疗MASH的潜在重磅药物。Lanifibranor对很多MASH相关肝脏病变取得了积极结果，并分别于2019年9月和2020年10月获得FDA治疗MASH的快速通道和突破性疗法认定。与MASH的其它III期试验药物相比，lanifibranor的优势在于它对脂肪性肝炎和纤维化都有改善作用。Lanifibranor目前正在进行一项关键的III期临床试验NATiV3，用于治疗成年 MASH患者。预计将于2026年在美国上市。2022年9月，Inventiva Pharma与正大天晴药业集团股份有限公司签订独家许可及合作协议，授权后者在中国开发和商业化Lanifibranor。•　Azemiglitazone potassium（MSDC-0602K）开发商：Cirius Therapeutics阶段：III期图4. Azemiglitazone potassium化学结构Azemiglitazone potassium（MSDC-0602K，图4）是第二代胰岛素增敏剂（insulin sensitizer），可以减少第一代胰岛素增敏剂的副作用，如水肿、骨折和低血糖。胰岛素增敏可以改善MASH。在目前对MASH患者的研究中，MSDC-0602K并未显示出对肝脏组织学有显著影响（活检技术）。但它仍然为未来研究的设计获取了有益的探索。MSDC-0602K显著降低了空腹血糖、胰岛素、糖化血红蛋白和肝损伤标志物，并且没有剂量限制性副作用。故而MSDC-0602K仍然有可能成为MASH患者的有效治疗选择。Cirius Therapeutics目前正在对MSDC-0602K进行III期评估，预计可能于2026年在美国上市。•　Vonafexor (EYP001)开发商：Enyo Pharma阶段：II期图5. Vonafexor化学结构Vonafexor（EYP001，图5）由Enyo Pharma开发，是一种口服合成非甾体、非胆汁酸FXR受体激动剂小分子，也在针对MASH 开发。与其他FXR受体激动剂不同的是，Vonafexor对肾功能 (eGFR)、炎症以及肝脏和内脏脂肪纤维化（MASH患者的IIa期LIVIFY研究）以及CKD（慢性肾病）和Alport综合征（临床前研究）具有有益作用。Vonafexor已在MASH 治疗领域取得了可喜的成果。Vonafexor具有快速改善MASH患者肝功能和肝脂肪的潜力。目前正处于针对MASH患者CKD的II期临床阶段，预计将于2027年在美国上市。•　HPG1860开发商：雅创医药阶段：II期图6. HPG1860化学结构雅创医药的资产HPG1860（图6）针对MASH和PBC（原发性胆汁性胆管炎）适应症。HPG1860是一种非胆汁酸口服全FXR受体激动剂。在正在进行的II期RISE研究中，表现出良好耐受性和对肝脏脂肪含量的显著影响，同时也表现出令人满意的安全性。•　VK2809开发商：Viking Therapeutics阶段：II期图7. VK2809化学结构。VK2809 （图7）是Viking Therapeutics开发的一种选择性甲状腺激素β受体 (THR-β) 激动剂，正在研究用于治疗各种代谢和肝脏疾病，包括针对MASH患者的IIb期研究，于2023年5月宣布了积极的顶线结果。有可能于2028年在美国上市。•　BIO89-100（Pegozafermin）开发商：89bio, Inc.阶段：II期Pegozafermin是糖聚乙二醇化的FGF21 （成纤维细胞生长因子21）长效类似物。天然FGF21的半衰期仅为半小时。Pegozafermin在IIb期试验中获得了积极的顶线数据，有潜力成为MASH的治疗选择。预计将于2027年进入美国市场。•　Efruxifermin开发商：Akero Therapeutics, Inc阶段：II期Efruxifermin (EFX) 是Akero Therapeutics, Inc.的主导产品，是一种差异化的Fc-FGF21融合蛋白，经过工程设计可模拟天然FGF21。EFX目前正在两项 IIb期临床试验中对活检确诊的MASH患者进行评估。EMA于2020年10月将 efruxifermin指定为优先药物（PRIME）。次年FDA授予了它快速通道资格。2022年12月，efruxifermin获得FDA治疗MASH的突破性疗法认定。Efruxifermin是目前唯一正在评估用于MASH肝硬化前期和肝硬化患者的药物。如果获得批准，该药物有可能成为一种高度差异化、同类最佳的FGF21类似物，并成为治疗MASH的单一疗法。EFX可以通过单次治疗解决MASH发病机制的所有阶段，包括逆转纤维化、解决脂肪性肝炎以及协助恢复全身健康的新陈代谢。该药预计将于2027年在美国市场上市。参考文献：（上下滑动查看更多）1.Understanding Liver Disease’s New Names—NASH is now MASH. VCU. Aug. 2023.2.Introduction of new terminology for fatty liver diseases. British Liver Trust. 24. 06. 2023.3.Manalac, T. Intercept Cuts All NASH Investments, One-Third of Staff After Second FDA Rejection. BioSpace. 23. 06. 2023.4.Taylor, N. P. NASH market fattening up as wait for liver treatments drags on. FiercePharma. 04. 12. 2023.5.FDA Sets PDUFA Date for Drug to Treat Patients with NASH. Formulary Watch. 14. 09. 2023.6.Shah-Neville, W. Biotech’s battle against NASH: The ongoing pursuit of an effective treatment. Labiotech. 19. 10. 2023.7.DeFeudis, N. Madrigal says it's 'well on the way' to potential NASH launch ahead of FDA decision: #JPM24. Endpoint News. 11. 01. 2024.8.Castaneda, R. Can Novo Nordisk's blockbuster weight loss drug and other 8.GLP-1s also work in NASH? The answer is complicated. Endpoints News. 08. 09. 2023.9.Jensen, K. Novo taps Flagship startups to develop drugs for obesity, MASH. BiopharmaDive. 04. 01. 2024.10.Nonalcoholic Steatohepatitis (NASH) Market to Observe Stunning Growth by 2032 Owing to a Robust Pipeline. BioSpace. 01. 11. 2023.近期直播推荐:

2024-01-03

·Business Wire

ENYO Pharma Announces a €39 Million Series C Financing and FDA Clearance to Advance Vonafexor in a Phase 2 Clinical Trial for Patients With Alport Syndrome

LYON, France--( BUSINESS WIRE )--ENYO Pharma (“ENYO”) announced that it has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 clinical study of Vonafexor, a highly selective FXR agonist, for the treatment of Alport Syndrome. Furthermore, ENYO announced the first closing of a 39 million € Series C equity financing, positioning ENYO as an emerging biotechnology company in the field of renal diseases. The financing will support the Phase 2 Alpestria-1 study and further profiling of Vonafexor in other kidney diseases, such as Autosomal Dominant Polycystic Kidney Disease (ADPKD). The financing was co-led by OrbiMed and Morningside Ventures with participation from other existing investors including AndEra Partners, Bpifrance InnoBio and Bpifrance Large Ventures. The clearance of ENYO’s IND represents a significant milestone for the company as it embarks on its first clinical trial focusing on renal disease. ENYO’s lead candidate Vonafexor, as well as fast follower EYP651, are highly specific FXR agonists given as once-daily oral treatments. Both compounds have strong fibrolytic and anti-inflammatory properties that are broadly applicable across several renal diseases. Vonafexor effect on renal function (eGFR) was already shown in the Phase 2 LIVIFY study of patients with both kidney impairment and fibrotic liver disease. Preclinical studies in both Alport syndrome and Chronic Kidney Disease mouse models showed beneficial effects of Vonafexor on kidney remodeling and function in a curative mode. In 2023, Vonafexor was granted as Orphan Drug Designation (ODD) by both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for Alport syndrome. ” We are delighted with this support from our existing investors” said Dr. Jacky Vonderscher, CEO at ENYO Pharma. “ There are huge unmet needs in many kidney diseases with fibrosis or inflammatory components. These patients almost invariably progress to end-stage kidney disease despite current therapies. The results already obtained with Vonafexor, our highly differentiated anti-inflammatory and fibrolytic lead compound, in patients with moderate kidney impairment and in several preclinical protocols, make us confident that it will greatly benefit to those patients with rare kidney diseases like Alport syndrome. “ ” Kidney diseases were somewhat neglected for decades, and it is refreshing to see a team like ENYO pursuing with persistence the development of Vonafexor for the benefit of these patients. “ said Iain Dukes of OrbiMed . About ENYO Pharma: For more information : ENYO Pharma – Developing therapeutics for diseases with impaired kidney function About OrbiMed: For more information : OrbiMed

临床2期孤儿药临床申请

2021-01-13

·GlobeNewswire

Nonalcoholic Steatohepatitis Drug Pipeline Analysis Review, 2020

Los Angeles, USA , Jan. 13, 2021 (GLOBE NEWSWIRE) -- Nonalcoholic Steatohepatitis Drug Pipeline Analysis Review, 2020 NASH Drug Pipeline Shows Promise as 95+ companies are working for Nonalcoholic Steatohepatitis Drug Development “Nonalcoholic Steatohepatitis (NASH) Pipeline Insight, 2020” by DelveInsight highlights the details around the NASH pipeline scenario, unmet needs, and NonAlcoholic Steatohepatitis therapeutic assessment of the key pipeline therapies. Some of the key Nonalcoholic Steatohepatitis Pipeline Highlights Nonalcoholic Steatohepatitis (NASH) is a form of fatty liver disease that can cause inflammation, and over the long term, can lead to scarring of the liver. Nonalcoholic Steatohepatitis symptoms include fatigue and pain in the upper right abdomen. There is no standard treatment for NASH patients, but lifestyle changes have influenced its progression. Get access to NASH Treatment Pipeline Sample Report NASH Pipeline Therapeutics ENYO Pharma develops EYP001, which is an orally bioavailable synthetic non-steroidal, non-bile acid FXR agonist small molecule that is also developed for NASH. FXR agonists could become the backbone of any future NASH therapies. The pioneering ENYO founding team discovered that FXR agonists interfere with the interaction between FXR and HBx, a hepatitis B viral protein essential for replicating the virus. It has demonstrated its efficacy in a Stelic mouse model (STAMTM) with a significant positive impact on most of the NASH key parameters (Fibrosis, Steatosis, Inflammation, Ballooning, triglycerides, and NAS). It differentiates from other FXR agonists with a potentially better C4/FGF19 balance. To learn more about NASH Drugs Development, request NASH Treatment Pipeline Sample Report Scope of Nonalcoholic Steatohepatitis Drug Pipeline Report Key Questions regarding Current NASH Treatment Landscape and Emerging Therapies Answered in the Pipeline Report Table of Contents Browse Detailed TOC, Emerging Drugs and Key Companies @ NASH Pipeline Scenario Related Reports DelveInsight's Nonalcoholic Steatohepatitis (NASH) Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and in depth understanding of historical and forecasted epidemiology. DelveInsight's Nonalcoholic Steatohepatitis (NASH) Epidemiology Forecast 2030 report delivers an in-depth understanding of the disease, historical, and forecasted epidemiology of Nonalcoholic Steatohepatitis (NASH) in the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan. DelveInsight' s Non Alcoholic Fatty Liver Disease (NAFLD) Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and in depth understanding of historical and forecasted epidemiology. DelveInsight's Non Alcoholic Fatty Liver Disease (NAFLD) Epidemiology Forecast 2030 report delivers an in-depth understanding of the disease, historical, and forecasted epidemiology of Non Alcoholic Fatty Liver Disease (NAFLD) in the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan. Non Alcoholic Fatty Liver Disease (NAFLD) Global API Manufacturers, Marketed and Phase III Drugs Landscape, 2020 " report by DelveInsight offers comprehensive insights on marketed and Phase III products for Non Alcoholic Fatty Liver Disease (NAFLD). Non Alcoholic Fatty Liver Disease (NAFLD) Pipeline Insight, 2020 report by DelveInsight outlays comprehensive insights of present clinical development scenario and growth prospects across the Non Alcoholic Fatty Liver Disease (NAFLD) market. DelveInsight's Hepatitis C Market Insights, Epidemiology and Market Forecast - 2030 report provides detailed insights on historical and forecasted epidemiology. About DelveInsightDelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing end to end comprehensive solutions to improve their performance.

小分子药物

100 项与 Vonafexor 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
Alport 综合征	临床2期	美国	ENYO Pharma SA初创企业	2024-06-06
Alport 综合征	临床2期	法国	ENYO Pharma SA初创企业	2024-06-06
Alport 综合征	临床2期	德国	ENYO Pharma SA初创企业	2024-06-06
Alport 综合征	临床2期	西班牙	ENYO Pharma SA初创企业	2024-06-06
慢性乙型肝炎	临床2期	澳大利亚	ENYO Pharma SA初创企业	2020-05-12
慢性乙型肝炎	临床2期	中国香港	ENYO Pharma SA初创企业	2020-05-12
慢性乙型肝炎	临床2期	波兰	ENYO Pharma SA初创企业	2020-05-12
慢性乙型肝炎	临床2期	韩国	ENYO Pharma SA初创企业	2020-05-12
非酒精性脂肪性肝炎	临床2期	美国	ENYO Pharma SA初创企业	2019-01-30
非酒精性脂肪性肝炎	临床2期	比利时	ENYO Pharma SA初创企业	2019-01-30

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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


NCT03812029 (CTgov)	临床2期	非酒精性脂肪性肝炎	120	Placebo (Placebo Part B)	簾簾製築窪範積廠壓繭(簾選憲鑰鏇鹽鹹築製齋) = 鹽製壓遞鹹繭遞餘網鬱築窪獵構齋製築積襯艱 (觸鏇窪製醖糧襯鏇窪鹽, 顧願獵遞獵膚壓獵網顧 ~ 廠積選衊廠蓋醖廠窪齋) 更多	-	2023-05-06
				Vonafexor (Vonafexor 100 mg QD Part B)	簾簾製築窪範積廠壓繭(簾選憲鑰鏇鹽鹹築製齋) = 繭獵簾壓窪鑰鹹構顧願築窪獵構齋製築積襯艱 (觸鏇窪製醖糧襯鏇窪鹽, 繭夢簾遞築齋觸鏇鹽獵 ~ 積簾構衊網鹽齋觸鹹鑰) 更多
NCT04465916 (CTgov)	临床2期	慢性乙型肝炎	26	Nucleotide analogue (Entecavir or Tenofovir Disoproxil)+EYP001a (Experimental Arm)	憲網蓋製艱築觸簾齋艱(築蓋積製醖襯廠憲壓鏇) = 顧廠蓋淵顧願鬱淵鹽衊齋鹽鏇網繭構築衊網醖 (積範淵鹽廠艱鏇窪築醖, 艱願艱顧觸艱鑰廠遞鏇 ~ 獵衊窪範積壓選膚鬱壓) 更多	-	2022-10-12
				Nucleotide analogue (Entecavir or Tenofovir Disoproxil) (Control Arm)	憲網蓋製艱築觸簾齋艱(築蓋積製醖襯廠憲壓鏇) = 簾選夢蓋鑰餘顧鹽鑰鑰齋鹽鏇網繭構築衊網醖 (積範淵鹽廠艱鏇窪築醖, 築構艱願壓壓積積艱顧 ~ 簾獵鏇選鹽鑰淵艱築襯) 更多
NCT04365933 (EYP001-203, BusinessWire) 人工标引	临床2期	慢性乙型肝炎	20	Entecavir+Peginterferon alfa-2a+Vonafexor	遞鏇築餘願襯淵壓觸鬱(廠簾艱糧鹹築襯鏇襯選) = 鹹蓋鑰憲窪餘艱艱鹹醖夢鬱構顧積築願鑰醖艱 (齋壓鹽簾築鏇積壓艱觸 )	积极	2021-07-30
				Peginterferon alfa-2a+Vonafexor	遞鏇築餘願襯淵壓觸鬱(廠簾艱糧鹹築襯鏇襯選) = 鏇觸廠餘選襯鑰鏇顧淵夢鬱構顧積築願鑰醖艱 (齋壓鹽簾築鏇積壓艱觸 )