A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics and Safety of K-808 (Pemafibrate) in Subjects With Primary Biliary Cholangitis With Compensated Cirrhosis and Without Cirrhosis

A Trial to Investigate the Pharmacokinetics (PK) Effects and Safety Profile of K-808 (Pemafibrate) in Primary Biliary Cholangitis (PBC) Subjects with and without Cirrhosis.

开始日期2024-10-01

申办/合作机构

Kowa Research Institute, Inc.

NCT06247735

/ Recruiting临床2期

A Phase 2, Randomized, Placebo-controlled, Parallel Group, Multicenter 12-week Study With a 52-week Extension to Evaluate the Efficacy and Safety of Two Doses of K-808 (Pemafibrate) in Subjects With Primary Biliary Cholangitis With Inadequate Response to Ursodeoxycholic Acid and/or Obeticholic Acid Treatment

Study to investigate the efficacy and safety of two doses of K-808 (pemafribate) in subjects with PBC.

开始日期2024-02-07

申办/合作机构

Kowa Research Institute, Inc.

JPRN-jRCT1061230070

/ SuspendedN/AIIT

The effects Of sodium-glucose coTransporter 2 inhibiTOR on fastIng Hepatic Insulin Clearance in type 2 diabetes - TOTTORI-HIC study

开始日期2023-10-31

申办/合作机构

Kowa Co., Ltd.

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项与 Kowa Co., Ltd. 相关的文献（医药）

2025-06-01·Experimental Eye Research

Ripasudil does not induce phospholipid accumulation in human corneal epithelial cells

Article

作者: Kasano, Atsushi ; Watanabe, Yuichiro ; Kanazawa, Mizuho ; Tazoe, Fumiko ; Inoue, Toshihiro ; Inoue, Noriyuki

Rho-associated coiled-coil-containing protein kinase (Rho kinase; ROCK) inhibitors represent a novel class of glaucoma medications that lower intraocular pressure by enhancing aqueous humor outflow through the conventional outflow pathway. Netarsudil, a ROCK inhibitor, is known to induce cornea verticillata as an adverse effect in clinical settings. Unlike systemic amiodarone and antimalarials, topical agents do not typically induce the development of this corneal condition. This study investigated whether ripasudil, another ROCK inhibitor, induces cornea verticillata using a Chinese hamster-derived ovary cell line (CHO-K1), SV40 transformed human corneal epithelial cell line (HCE-T), and normal human primary corneal epithelial cells (HCEC-2). CHO-K1, HCE-T, and HCEC-2 were treated with ripasudil, netarsudil, or Y-27632 with varying concentrations (0.1, 0.3, 1, 3, 10, or 30 μM). Ripasudil and Y-27632 did not alter intracellular phospholipid levels at any concentration tested. Conversely, intracellular phospholipid accumulation was observed in cells treated with netarsudil. Netarsudil possesses chemical characteristics similar to those of cationic amphiphilic drugs, which are known to cause phospholipidosis. In contrast, ripasudil and Y-27632 lack these structural features. Our results suggest that ripasudil has a low likelihood of inducing cornea verticillata.

2025-04-21·Cancer Research

Abstract 1798: K-679: A novel, ultra-high-DAR antibody drug-loaded unimicelle conjugate (ADUC) enabling more effective treatment in EGFR-expressing solid tumors compared to general ADCs

作者: Fujimaki, Nobuhiro ; Mori, Masato ; Suzuki, Kenichi ; Hosono, Kahori ; Shiraishi, Madoka ; Yoshida, Hideo ; Tamiya, Masaki ; Higashi, Hideyuki

AbstractBackground:Conventional antibody-drug conjugates (ADCs) face significant challenges in treating solid tumors due to heterogeneous antigen expression or low antigen levels, resulting in suboptimal targeting and reduced therapeutic efficacy. While increasing the drug-to-antibody ratio (DAR) could enhance efficacy, traditional high-DAR approaches often compromise pharmacokinetics due to increased hydrophobicity and molecular size. To address these limitations, we engineered a novel platform technology: a compact, 20-nm antibody drug-loaded unimicelle (unimer-micelle) conjugate (ADUC) utilizing single-chain polymer nanoparticles. This platform achieves an unprecedented DAR of approximately 40 while maintaining favorable physicochemical properties. Using this platform, we developed K-679, which combines cetuximab with DM1-loaded unimicelles.Methods:Antigen-binding specificity and cellular internalization of K-679 were evaluated using surface plasmon resonance, flow cytometry, and fluorescence microscopy. In vitro cytotoxicity, in vivo anti-tumor activities, pharmacokinetics, and biodistribution were investigated in multiple human cancer cell lines and xenograft models. The bystander killing effect was quantified using an in vivo imaging system in mice co-inoculated with EGFR-positive and luciferase-expressing EGFR-negative cells. The benchmark ADCs were prepared by conventional conjugation of cetuximab with DM1.Results:K-679 exhibited EGFR-binding affinity equivalent to that of unconjugated cetuximab, efficient cellular internalization, and triggered cell-cycle arrest, apoptosis, and cell-growth inhibition in EGFR-positive cells, even in chemotherapeutic drug-resistant lines. In vivo studies demonstrated superior tumor-targeted delivery compared to conventional antibodies, and efficient payload release in tumors with minimal DM1 levels in circulation. This resulted in potent anti-tumor effects across multiple EGFR-positive tumor xenograft models, while showing no activity in EGFR-negative models. These observations reveal that K-679 mediates its anti-tumor effects in an EGFR-dependent manner through DM1-mediated cytotoxicity. Notably, K-679 showed significant bystander killing of EGFR-negative cells within heterogeneous tumors and exhibited efficacy in EGFR-low tumor models in which benchmark ADCs proved ineffective. Comparative studies further highlighted that K-679 outperformed lower-DAR variants at equivalent payload doses.Conclusion:Our findings establish K-679 as a promising therapeutic candidate for heterogeneous EGFR-expressing solid tumors, characterized by a more potent anti-tumor effect through an exceptionally high DAR, enhanced drug accumulation into tumors and significant bystander effect.Citation Format:Hideo Yoshida, Kenichi Suzuki, Kahori Hosono, Nobuhiro Fujimaki, Masaki Tamiya, Madoka Shiraishi, Hideyuki Higashi, Masato Mori. K-679: A novel, ultra-high-DAR antibody drug-loaded unimicelle conjugate (ADUC) enabling more effective treatment in EGFR-expressing solid tumors compared to general ADCs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1798.

2025-03-01·Journal of Atherosclerosis and Thrombosis

Clinical Pharmacology of Pemafibrate Extended-release Formulation in Patients with Hypertriglyceridemia—A Phase 2, Multicenter, Active-controlled, Randomized, Single-blind, Crossover study

Article

作者: Saito, Ayumi ; Suganami, Hideki ; Araki, Eiichi ; Minamikawa, Sara ; Yokote, Koutaro ; Tanigawa, Ryohei ; Ishibashi, Shun ; Yamashita, Shizuya ; Arai, Hidenori

AIMSEfficacy, safety, and pharmacokinetics of the selective PPARα modulator pemafibrate as once-daily extended-release (XR) tablets were compared with those of twice-daily immediate-release (IR) tablets in patients with hypertriglyceridemia.METHODSA multicenter, randomized, single-blind, active-controlled crossover, phase 2 clinical pharmacology study was performed in patients with hypertriglyceridemia. Patients were randomly assigned to IR 0.2 mg/day, XR 0.4 mg/day, or XR 0.8 mg/day before/after meals (fasted/fed) and treated for a total of eight weeks. The primary endpoint was percentage change in fasting serum triglycerides (TG).RESULTSOf 63 randomized patients, 60 received the study drug. Patients were 78.3% male, mean age (±SD) 57.5±9.8 years, BMI 25.5±3.7 kg/m², and fasting TG 221.3±68.1 mg/dL. Fasting serum TG decreased significantly from baseline in all groups (LS mean [95% CI];-43.6 [-47.7, -39.5] % for IR 0.2 mg/day, -41.1 [-45.1, -37.0] % for XR 0.4mg/day, -39.7 [-43.8, -35.6] % for XR 0.8 mg/day), indicating that XR 0.4 and XR 0.8 mg/day were not inferior to IR 0.2 mg/day. TG-lowering effects tended to be stronger for fed than fasted administration. MRT_ss, t_max, and t_1/2 were longer for XR than for IR. Adverse events showed no major inter-group differences: 12.5% (5/40 patients) for IR 0.2, 17.5% (7/40) for XR 0.4, and 20.0% (8/40) for XR 0.8 mg/day.CONCLUSIONSIn patients with hypertriglyceridemia, XR substantially lowered TG at all doses, with maximum effectiveness at 0.4 mg/day, the dose approved in Japan, to a level comparable to IR 0.2 mg/day. There were no safety concerns up to 0.8 mg/day.

项与 Kowa Co., Ltd. 相关的新闻（医药）

2025-04-25

·生物制药进展杂评

全球药物研发进展周报摘要（2025.04.12-04.18）

全球批准1.Biogen公司Lecanemab获EMA批准上市，用于治疗经临床诊断为轻度认知障碍及轻度痴呆的早期阿尔茨海默病(AD)成人患者，且为载脂蛋白E ε4(ApoE ε4*)非携带者或杂合子，并经确认存在β-淀粉样蛋白病理；2.GSK公司Belantamab mafodotin获MHRA批准上市，用于治疗多发性骨髓瘤成年患者；3.Kowa Company公司Pemafibrate获NMPA批准上市，用于治疗血脂异常；4.康方生物Ebdarokimab获NMPA批准上市，用于治疗中重度斑块状银屑病成人患者；全球申报1.Regeneron公司Aflibercept获FDA消极反馈，用于治疗湿性年龄相关性黄斑变性(wAMD)和糖尿病性黄斑水肿(DME)；2.Scilex公司Colchicine获FDA孤儿药资格认定，用于治疗心包炎；3.百济神州Sonrotoclax获NMPA拟纳入优先审评，用于治疗既往接受过治疗的慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤(SLL)成人，以及治疗既往接受过抗CD20治疗和BTKi治疗的套细胞淋巴瘤(MCL)成人患者；4.华毅乐健GS1191-0445获NMPA拟纳入突破性治疗，用于治疗先天性凝血因子VII缺乏引起的血友病A；临床进展1.荣昌生物启动Disitamab Vedotin的III期临床研究，用于治疗HER2低表达的晚期胃/胃食管结合部腺癌；2.信达生物启动Mazdutide的III期临床，用于治疗中重度阻塞性睡眠呼吸暂停且肥胖;3.复宏汉霖完成HLX-22的II期临床首例患者给药，用于治疗HER2低表达HR阳性的局部晚期或转移性乳腺癌；4.恒瑞医药启动HRS-5817的I期临床，用于治疗肥胖；

上市批准优先审批临床3期突破性疗法孤儿药

2025-04-24

·CPHI制药在线

正大天晴抢报佩玛贝特片首仿，降脂药市场再掀波澜

关注并星标CPHI制药在线4月23日，南京正大天晴制药有限公司递交的佩玛贝特片的4类仿制药上市申请获CDE受理，这意味着国内佩玛贝特片首仿报产。原研佩玛贝特（pemafibrate，Parmodia）是日本兴和株式会社（Kowa Company）开发的一种新型、高选择性的过氧化物酶体增殖物激活受体α（PPARα）调节剂，通过与PPARα结合并调节参与脂质代谢的基因表达，显著改善血脂代谢。佩玛贝特能有效降低血浆甘油三酯（TG）水平，同时增加高密度脂蛋白胆固醇（HDL-C）水平，并对其他血脂指标产生积极影响。佩玛贝特被开发用于治疗高脂血症、非酒精性脂肪肝、高胆固醇血症和原发性胆汁性胆管炎等疾病。2022年11月《新英格兰医学杂志》（NEJM）上发表的PROMINENT试验结果显示：在合并2型糖尿病、TG轻中度升高（200~499mg/dl）、HDL-C水平偏低（≤40mg/dl），且均接受他汀类药物治疗的患者中，与安慰剂相比，佩玛贝特在4个月内将中位TG水平降低了26.2%，且对HDL-C等其他血脂参数也有积极改善。但相比安慰剂，在该研究中接受佩玛贝特治疗的患者的心血管事件发生率并没有降低。2017年7月，原研佩玛贝特普通片在日本获批治疗高脂血症。2023年6月，佩玛贝特的新剂型缓释片在日本获批治疗高脂血症（含家族性高脂血症）。相比佩玛贝特片每日口服2次，佩玛贝特缓释片给药更加方便，仅需口服1次。佩玛贝特上市后表现亮眼，据悉其2020年在日本的市场销售额就已超过非诺贝特，达到6510万美元，显示出良好的市场潜力。据IMS数据，2023年佩玛贝特片在日本的销售额达1.12亿美元，增长率10.83%。在国内，原研佩玛贝特片于2025年4月14日获批，用于治疗高脂血症（包括家族性高脂血症）。不足10日，国内就有佩玛贝特片仿制药报产，可见佩玛贝特片市场竞争十分激烈。相关阅读：《降脂新药佩玛贝特中国获批，能否重塑血脂治疗格局？》实际上，佩玛贝特仿制药竞争早就暗流涌动。据公开资料，佩玛贝特原研化合物专利于2024年9月到期，制剂组合物专利于2034年8月到期。据CDE官网药物临床试验登记与信息公示平台，国内已登记21项佩玛贝特片BE试验，其中12项已完成。南京正大天晴作为国内首家递交佩玛贝特片仿制药上市申请的企业，若顺利有望斩获佩玛贝特片首仿资格。这不仅可能改变当前血脂异常治疗的市场格局，也将为广大患者带来更多治疗选择和更具性价比的治疗方案，进一步提高患者的用药可及性。除面临仿制药竞争，佩玛贝特在血脂异常领域还面临着来自其他药物的竞争。佩玛贝特在降低TG方面疗效优异，而国内降低TG最常用的是贝特类药物，如苯扎贝特、非诺贝特、吉非罗齐、环丙贝特。但与传统贝特类药物非诺贝特相比，佩玛贝特对PPARα的选择性高2500倍，可大幅减少肝毒性和肌肉损伤等副作用风险。贝特类药物主要通过抑制内源性TG合成，降低血清TG、升高高密度脂蛋白（一种对抗动脉粥样硬化的脂蛋白）水平，促进极低密度脂蛋白和TG的分解，促进胆固醇从周围组织转运到肝脏代谢。而且，贝特类还有有抗血栓和抗炎作用等非调脂作用。据米内网数据，2022年全国贝特类药物销售额达8.1亿元，且呈逐年上升的趋势。此外，国内近年还批准了一些新的降脂药物，如新型PCSK9抑制剂（阿利西尤单抗、托莱西单抗等）。据悉国产PCSK9抑制剂的年治疗费用已降至2万元以下，未来佩玛贝特要想侵蚀PCSK9抑制剂市场，有可能会打价格战，尤其是未来随着国产佩玛贝特的获批上市。END【企业推荐】领取CPHI & PMEC China 2025展会门票来源：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~

专利到期

2025-04-16

·美迪西Medicilon

开盘上涨超120%，映恩生物正式登陆港交所 | 1分钟药闻速览

医线药闻4月14日，CDE官网公示，翰森制药申报的1类新药HS-10529片获批临床，拟开发治疗KRAS G12D突变的晚期实体瘤（胰腺癌、结直肠癌、非小细胞肺癌等）。近日，珠海贝海生物技术有限公司宣布，其具有完全自主知识产权的PDC偶联新药 BH259，已获得国家药品监督管理局药品审评中心（CDE）临床试验申请（IND）的批准。BH259 是一款全新的PDC多肽偶联药物，适应症为实体瘤。4月14日，新诺威控股子公司石药集团巨石生物制药有限公司申报的注射用SYS6041药品临床试验申请已获得美国FDA批准，可以在美国开展针对晚期实体瘤的临床试验。该药物是一款单克隆抗体偶联药物4月14日，NMPA官网显示，Kowa Company（兴和制药）公司研发的新药佩玛贝特片在中国正式获批。根据Kowa Company官网信息可知，该药本次获批的适应症为治疗血脂异常。投融药事4月15日，映恩生物正式以“9606”为股票代码在港交所主板挂牌上市。映恩生物在本次IPO中发行17,332,300股股份，相较早前的发行计划有所提升。其中，香港公开发售获115.14倍认购，国际发售获13.52倍认购。映恩生物成立于2019年，致力于为癌症和自身免疫性疾病等患者研发创新抗体偶联药物（ADC）。科技药研4月9日，Nature杂志的一项最新研究通过对近200万个体（48.9万病例，147.2万对照）开展全基因组关联分析（GWAS），发现了962个独立遗传关联信号（其中513个为新发现），并结合单细胞多组学、功能验证及临床数据分析，揭示了骨关节炎遗传机制的关键通路与潜在药物靶点。[1]Hatzikotoulas, K., Southam, L., Stefansdottir, L. et al. Translational genomics of osteoarthritis in 1,962,069 individuals. Nature (2025). https://doi.org/10.1038/s41586-025-08771-z

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