A Phase I Clinical Study to Evaluate the Pharmacokinetic Profile and Safety of Lanifibranor After Single Dose and Multiple Doses in Healthy Adult Chinese Subjects

This will be a randomized, open-label parallel design and single centre study conducted at the 1st hospital affiliated to Jilin University. Approximately 24 healthy Chinese volunteers, male and female will be recruited and divided into two equal groups (12 subjects per dose). The primary objective of this study is to evaluate the pharmacokinetic profile of lanifibranor after single dose and multiple doses 800 and 1200 mg in healthy adult Chinese subjects. The secondary objective is to evaluate the safety of lanifibranor after single dose and multiple doses 800 and 1200 mg in healthy adult Chinese subjects.

开始日期2023-10-31

申办/合作机构

正大天晴药业集团股份有限公司

CTR20233135

/ Completed临床1期

评价Lanifibranor在中国健康成人受试者中单次和多次给药的药代动力学特征和安全性的I期临床试验

主要目的评价Lanifibranor在中国健康成人受试者中单次、多次给药后的药代动力学特征（PK）。次要目的评价Lanifibranor在中国健康成人受试者中单次、多次给药后的安全性。

开始日期2023-10-27

申办/合作机构

Delpharm Reims SAS

[+4]

CTR20232876

/ Recruiting临床3期

一项评价 lanifibranor 在无肝硬化、伴 2 期（F2）/3 期（F3）肝纤维化的非酒精性脂肪性肝炎（NASH）成人受试者中有效性和安全性的多中心、随机、双盲、安慰剂对照加 lanifibranor扩展治疗的 III 期研究

本项 III 期研究旨在评价 lanifibranor 在 NASH 伴肝纤维化成人受试者中的作用. 主要队列两个周期的主要目的是：双盲安慰剂对照（DBPC）期（A 部分）评估与安慰剂相比，lanifibranor 在 NASH 缓解同时经肝组织学评估纤维化改善方面的效果。双盲试验药扩展（ATE）治疗期（B 部分）评估 DBPC 期后 lanifibranor 的安全性。

开始日期2023-09-28

申办/合作机构

Delpharm Reims SAS

[+4]

100 项与拉尼兰诺相关的临床结果

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100 项与拉尼兰诺相关的转化医学

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100 项与拉尼兰诺相关的专利（医药）

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项与拉尼兰诺相关的文献（医药）

2025-03-01·Journal of Hepatology

Metabolic effects and mechanism of action of the pan-PPAR agonist lanifibranor

作者: Gastaldelli, Amalia ; Sabatini, Silvia

2025-03-01·Clinical Gastroenterology and Hepatology

Biomarkers of Histological Response in Lanifibranor-treated Patients With Metabolic Dysfunction-associated Steatohepatitis

Article

作者: Patel, Sanjaykumar ; Roux, Marine ; Cooreman, Michael P ; Broqua, Pierre ; Abitbol, Jean-Louis ; Hervé, Hugo ; Huot-Marchand, Philippe ; Junien, Jean-Louis ; Dzen, Lucile ; Abdelmalek, Manal F ; Francque, Sven M ; Boursier, Jérôme

BACKGROUND & AIMSLanifibranor, a pan-peroxisome proliferator-activated receptor agonist, has demonstrated therapeutic efficacy on metabolic dysfunction-associated steatohepatitis (MASH) resolution and fibrosis improvement in the Phase IIb NATIVE study. The histologic endpoints of MASH resolution and fibrosis improvement (E1), MASH resolution without worsening of fibrosis (E2), and fibrosis improvement without worsening of MASH (E3) were investigated with the aim of identifying biological signatures of E1, E2, and E3 responders based on serum biomarkers in patients treated with lanifibranor.METHODSNATIVE evaluated lanifibranor 800 and 1200 mg daily vs placebo in patients with non-cirrhotic MASH treated over 24 weeks. Liver biopsy was obtained at baseline and the end of treatment. Patients receiving lanifibranor were pooled, and those with liver biopsies were selected (n = 142). A panel of 65 biomarkers were evaluated by assessing baseline and absolute as well as relative changes at the end of treatment.RESULTSThe biomarkers included in E1 score (baseline adiponectin and ferritin; delta of matrix metalloproteinase 9 and transferrin), E2 score (baseline cytokeratin 18 Fragment M65; delta of hyaluronic acid, fructosamine, and alanine aminotransferase), and E3 score (baseline cytokeratin 18 Fragment M65 and gamma-glutamyl transferase; delta of aspartate aminotransferase, insulin, and urea) represented metabolic, apoptotic, and fibrosis aspects of the disease. These signatures provided good accuracy for the noninvasive identification of histologic response under lanifibranor with area under the receiver operating characteristic curve at 0.81 ± 0.08 for E1 score, 0.80 ± 0.08 for E2 score, and 0.81 ± 0.08 for E3 score.CONCLUSIONSResults from this analysis show evidence that baseline values and changes in selected serum biomarkers can aid in predicting histologic response in MASH under lanifibranor treatment. These findings support utilizing a similar approach in a larger sample size (NATiV3, NCT03008070).

2025-02-01·Biomedicine & Pharmacotherapy

The pan-PPAR agonist lanifibranor reduces portal pressure independent of fibrosis reduction through the splanchnic vasculature

Article

作者: Junien, Jean-Louis ; Verhelst, Xavier ; Van Vlierberghe, Hans ; Raevens, Sarah ; Lefere, Sander ; Geerts, Anja ; De Bruyne, Ruth ; Casteleyn, Christophe ; Vanhove, Christian ; Neyt, Sara ; Wettstein, Guillaume ; Descamps, Benedicte ; Antwi, Milton ; Devisscher, Lindsey ; Heldens, Anneleen ; Onghena, Louis

Portal hypertension (PH) can cause severe complications in patients with advanced chronic liver disease (aCLD). The pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor reduces portal pressure in preclinical models of aCLD. Since the effect on PH might be secondary to fibrosis improvement, we investigated the effect of lanifibranor on PH, hepatic and splanchnic angiogenesis in mouse models of fibrotic and prehepatic non-fibrotic PH. Mice with fibrotic PH (common bile duct ligation; CBDL) and prehepatic PH (partial portal vein ligation; PPVL) received daily lanifibranor/vehicle for 14 or 7 days, respectively. Hemodynamics, serum, hepatic and mesenteric histology, and hepatic, mesenteric and liver sinusoidal endothelial cells (LSEC) gene expression levels were analyzed. Vascular corrosion casts of the venous mesenteric and hepatic vasculature were analyzed using scanning electron microscopy and µCT. Portal pressure was increased in CBDL mice. Lanifibranor treatment demonstrated a dose-dependent trend towards decreasing the elevated portal pressure, and reduced fibrosis. Hepatic mRNA levels of inflammatory, fibrotic and angiogenic markers were significantly downregulated in lanifibranor-treated CBDL mice. LSEC dysfunction was improved by lanifibranor. Compared to CBDL mice, portal pressure was more extensively elevated in PPVL mice, which was significantly reduced by lanifibranor. Superior mesenteric artery blood flow, which was increased in vehicle-treated PPVL mice, tended to decrease by lanifibranor. The expansion of the mesenteric vasculature and mesenteric protein level of angiogenetic markers in PPVL mice were reduced after lanifibranor. In conclusion, lanifibranor improves PH, independently from fibrosis reduction, potentially through reducing the venous mesenteric vasculature expansion and intrahepatic angiogenesis, and ameliorating LSEC function.

177

项与拉尼兰诺相关的新闻（医药）

2025-03-02

·药明康德

使癌症之王复发风险降低近90%的组合疗法；一次治疗恢复遗传性失聪儿听力的基因疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 个体化新抗原疫苗autogene cevumeran的1期临床试验最新结果积极，在接受手术切除肿瘤的胰腺导管腺癌（PDAC）患者中，中位随访时间为3.2年时，对该疫苗产生应答患者的疾病复发风险与未产生应答的患者相比降低86%。 2. 用于治疗遗传性耳聋的在研基因疗法DB-OTO的1/2期临床试验数据亮眼，在11名接受治疗后疗效可评估的患儿中，10人表现出显著的听力改善。 3. 在研基因疗法rAAV8.hRKp.AIPL1用于治疗AIPL1相关严重视网膜营养不良（LCA4），在首个人体试验中使所有11名先天失明儿童的治疗眼均获得了视力改善。药明康德内容团队整理 Autogene cevumeran（BNT122）：公布1期临床试验的新数据纪念斯隆凯特琳癌症中心（MSKCC）科学家领衔的研究团队，在《自然》期刊上发表了由BioNTech和罗氏（Roche）联合开发的个体化新抗原疫苗autogene cevumeran（BNT122）的1期临床试验最新结果。Autogene cevumeran是基于BioNTech的iNeST癌症疫苗技术平台生成的个体化新抗原疫苗。该公司的mRNA新抗原疫苗可在一个mRNA分子里编码数十种新抗原，从而激发人体针对肿瘤细胞产生更为全面的免疫反应，防止肿瘤细胞逃避免疫系统的攻击。在这项1期临床试验中，研究人员给19名接受过手术治疗的PDAC患者使用了抗PD-L1抗体atezolizumab的治疗，其中16人接受了随后的autogene cevumeran治疗。在这16名患者中，有15人此后还接受了化疗。在2023年发表的研究显示，16名接受癌症疫苗治疗的患者中有8人（50%）产生了T细胞反应，被认为是这种癌症疫苗治疗的应答患者。近日发布的论文公布了这些患者的3年随访数据，结果表明，autogene cevumeran能够持续降低患者的疾病复发风险。在中位随访时间为3.2年时，对该疫苗产生应答的PDAC患者的疾病复发风险与未产生应答的患者相比，降低了86%。两组患者的中位总生存期（OS）均尚未达到。 ▲接受mRNA癌症疫苗治疗患者的无复发生存期（RFS）和OS数据（图片来源：参考资料[2]） DB-OTO：公布1/2期临床试验的新数据再生元（Regeneron Pharmaceuticals）公布了其用于治疗遗传性耳聋的在研基因疗法DB-OTO的1/2期临床试验的新数据。DB-OTO是一种在研细胞选择性腺相关病毒（AAV）基因疗法，旨在通过AAV载体将OTOF基因的健康拷贝传递至耳蜗毛细胞，为因OTOF基因突变导致的先天性深度听力损失患者提供持久的生理性听力。此前，DB-OTO已获得了FDA的孤儿药资格、罕见儿科疾病认定、快速通道资格和再生医学先进疗法认定，以及欧洲药品管理局授予的孤儿药资格。截至目前，该试验中已有12名10个月至16岁的患儿接受了DB-OTO治疗，其中9人单耳接受了耳蜗内注射，3人双耳接受了注射。在11名接受治疗后疗效可评估的患儿中，10人表现出显著的听力改善。在接受24周评估的5名患儿中，3人的平均听力阈值改善至接近正常或正常水平。首例在10个月大时就接受治疗的患儿在治疗后48周时，听力改善已接近正常水平，尤其是关键的语音相关频率范围内的听力水平。该患儿的语言感知测试结果从第48周到第72周表现出进一步的改善，孩子已能够在对话中正确识别出“妈妈”、“饼干”和“飞机”等词语，且无需任何视觉提示。安全性方面，在所有12名受试者中，手术和DB-OTO均表现出良好的耐受性，未发生与DB-OTO相关的不良事件或严重不良事件。5名患者经历了短暂的手术后前庭不良事件（如眼球震颤、恶心、头晕、呕吐），这些症状在给药后6天内消失。 rAAV8.hRKp.AIPL1：公布首个人体临床试验结果 MeiraGTx公司宣布，其在研基因疗法rAAV8.hRKp.AIPL1用于治疗AIPL1相关严重视网膜营养不良的首个人体临床试验结果在《柳叶刀》期刊上发表。由AIPL1基因缺陷导致的视网膜营养不良会从出生起严重影响视力。rAAV8.hRKp.AIPL1利用重组腺相关病毒载体，递送由人类视紫红质激酶启动子调控的人类AIPL1转基因。该论文报告了首批单眼接受rAAV8.hRKp.AIPL1治疗的4名儿童的相关数据。接受治疗前，他们的双眼视力仅限于对光的感知。接受治疗平均3.5年后，其治疗眼的视力平均改善至LogMAR评分0.9，而未治疗眼在最终随访时的视力无法测量。LogMAR是检测视力的评分系统，数值变小说明视力改善。正常视力的LogMAR评分为0，而干预前患者的LogMAR为2.7。另外，还有7名患有LCA4的儿童双眼接受了治疗。所有11名先天失明儿童的治疗眼均获得了视力改善。 ▲接受rAAV8.hRKp.AIPL1治疗的四名儿童的视力检测结果（图片来源：参考资料[4]） Versamune HPV、PDS01ADC：公布1/2期联合治疗试验数据 PDS Biotechnology公司宣布，其HPV16靶向免疫疗法Versamune HPV、IL-2融合抗体偶联药物（ADC）PDS01ADC联用PD-L1免疫检查点抑制剂（ICI）的临床研究结果已发表在JAMA Oncology上。这项由美国国家癌症研究所（NCI）领导的临床试验评估了该三联疗法在复发性/转移性HPV相关癌症（包括肛门癌、宫颈癌、头颈癌等）患者中的疗效。此次公布的试验结果显示，该三联疗法在HPV16阳性患者中表现出显著的临床效益。在14名未接受过ICI治疗的患者中，中位OS达到42.4个月，高于历史结果的7-12个月。在8名未接受过ICI治疗的HPV16阳性患者中，中位OS尚未达到。在ICI耐药的患者中，中位OS为17个月，优于历史结果的3-4个月。此外，未接受过ICI治疗的HPV16阳性患者的客观缓解率（ORR）达75%，历史上发表的结果为11-24%。 LTZ-301：IND申请获得FDA许可 LTZ Therapeutics公司宣布美国FDA已批准其LTZ-301的IND申请，初步研究将在无标准疗法可用或标准治疗失败的复发/难治性非霍奇金淋巴瘤（r/r NHL）患者中进行。LTZ-301是一种新型的髓系细胞接合双特异性抗体，通过增强Fcγ受体（FcγR）非依赖性抗体依赖性细胞吞噬作用（ADCP）来清除CD79b阳性B细胞。CD79b是一种独特的肿瘤抗原受体，在B细胞恶性肿瘤中高度表达，包括接受现有CD19或CD20靶向疗法治疗后复发或耐药的肿瘤细胞。LTZ-301通过将单核细胞和巨噬细胞重新定向至CD79b阳性B细胞，从而增强这些免疫细胞的吞噬作用并清除癌细胞。临床前研究表明，LTZ-301在体外和体内实验中均表现出强效的药理活性，并具有良好的安全性。 ADCE-T02：IND申请获得FDA许可 Adcendo公司宣布，美国FDA已批准ADCE-T02的IND申请，可在晚期实体瘤患者中开展1期临床试验。组织因子（TF）在膀胱癌、非小细胞肺癌、结直肠癌、宫颈癌、食管癌、头颈癌和胃肠道癌等过度表达，但在正常组织中表达受限，因此是表现优异的ADC靶点。ADCE-T02是一种新型、高度差异化的TF靶向ADC，其独特的抗体设计能够减弱对凝血通路的影响。同时，T1000-exatecan连接子-有效载荷技术平台经研究证明，能够放大“旁观者效应”、提高连接子稳定性，并具备克服耐药性机制的潜力。这些差异化的特性有望转化为更高的临床治疗应答率、更长的疗效持续时间以及更好的安全性，拥有更优异的治疗窗口。2024年8月，Adcendo与普众发现达成超10亿美元的许可协议，获得在大中华区以外ADCE-T02的全球独家开发和商业化权利。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] In Early-Phase Pancreatic Cancer Clinical Trial, Investigational mRNA Vaccine Induces Sustained Immune Activity in Small Patient Group. Retrieved February 21, 2025, from https://www.mskcc.org/news/can-mrna-vaccines-fight-pancreatic-cancer-msk-clinical-researchers-are-trying-find-out [2] Sethna et al., (2025). RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer. Nature, https://doi.org/10.1038/s41586-024-08508-4 [3] MeiraGTx Announces The Lancet Publication of Data Demonstrating the Efficacy of rAAV8.hRKp.AIPL1 for the Treatment of Leber Congenital Amaurosis 4 (LCA4) Retinal Dystrophy. Retrieved February 21, 2025, from https://www.globenewswire.com/news-release/2025/02/21/3030330/0/en/MeiraGTx-Announces-The-Lancet-Publication-of-Data-Demonstrating-the-Efficacy-of-rAAV8-hRKp-AIPL1-for-the-Treatment-of-Leber-Congenital-Amaurosis-4-LCA4-Retinal-Dystrophy.html [4] Michaelides et al., (2025). Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study. The Lancet, DOI: 10.1016/S0140-6736(24)02812-5 [5] Latest DB-OTO Results Demonstrate Clinically Meaningful Hearing Improvements in Nearly All Children with Profound Genetic Hearing Loss in CHORD Trial. Retrieved February 28, 2025, from https://investor.regeneron.com/news-releases/news-release-details/latest-db-oto-results-demonstrate-clinically-meaningful-hearing [6] PDS Biotech Announces Positive Clinical Data Demonstrating Compelling Survival and Clinical Responses in Recurrent/Metastatic HPV-Associated Cancers Published in JAMA Oncology. Retrieved February 28, 2025, from https://www.pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/132-2025-news/971-iotechnnouncesositivelinicalataemonstrating20250226 [7] LTZ Therapeutics Announces FDA Clearance of IND Application to Initiate Trial of First-in-Class Myeloid Engager Immunotherapy, LTZ-301. 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Retrieved February 28, 2025, from https://www.globenewswire.com/news-release/2025/02/20/3030046/0/en/Inventiva-and-Hepalys-Pharma-Inc-announce-the-initiation-of-the-clinical-development-program-of-lanifibranor-in-Japan-with-the-dosing-of-the-first-participant-in-Phase-1-trial.html [10] Calidi Biotherapeutics Announces Commencement of Recruitment for Multiple Dose CLD-101 Trial in Patients with Newly Diagnosed High Grade Glioma at Northwestern University Hospital. Retrieved February 28, 2025, from https://www.globenewswire.com/news-release/2025/02/24/3031073/0/en/Calidi-Biotherapeutics-Announces-Commencement-of-Recruitment-for-Multiple-Dose-CLD-101-Trial-in-Patients-with-Newly-Diagnosed-High-Grade-Glioma-at-Northwestern-University-Hospital.html [11] Synnovation Therapeutics Announces Second Program to Enter the Clinic: First Patient Dosed in Phase I Trial with SNV4818, a Potential Best-In-Class Pan-Mutant-Selective PI3Kα Inhibitor for the Treatment of Solid Tumors. 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Retrieved February 28, 2025, from https://investor.assemblybio.com/news-releases/news-release-details/assembly-biosciences-doses-first-participant-phase-1a-clinical [15] ProMIS Neurosciences Doses First Patients in Phase 1b PRECISE-AD Trial of PMN310 for Alzheimer’s Disease. Retrieved February 28, 2025, from https://www.promisneurosciences.com/news-media/press-releases/detail/239/promis-neurosciences-doses-first-patients-in-phase-1b [16] TIXiMED Inc. Announces Successful Dosing of First Cohort in the Phase 1 Clinical Trial of TIX100, its Investigational Disease-Modifying Treatment for Type 1 Diabetes. Retrieved February 28, 2025, from https://www.businesswire.com/news/home/20250227506831/en/TIXiMED-Inc.-Announces-Successful-Dosing-of-First-Cohort-in-the-Phase-1-Clinical-Trial-of-TIX100-its-Investigational-Disease-Modifying-Treatment-for-Type-1-Diabetes [17] Significant milestone reached for EG 427 with first patient treated with EG110A, first non-replicative herpes vector based genetic medicine for the treatment of neurogenic bladder. Retrieved February 28, 2025, from https://www.globenewswire.com/news-release/2025/02/27/3033525/0/en/Significant-milestone-reached-for-EG-427-with-first-patient-treated-with-EG110A-first-non-replicative-herpes-vector-based-genetic-medicine-for-the-treatment-of-neurogenic-bladder.html [18] Hemab Therapeutics Announces Start of Velora Pioneer, a Phase 1/2 Clinical Trial Investigating HMB-002 for the Treatment of Von Willebrand Disease. Retrieved February 28, 2025, from https://www.prnewswire.com/news-releases/hemab-therapeutics-announces-start-of-velora-pioneer-a-phase-12-clinical-trial-investigating-hmb-002-for-the-treatment-of-von-willebrand-disease-302387425.html [19] Ensho Therapeutics Announces Presentation of Data Highlighting NSHO-101 as a Once-Daily Oral Agent for the Potential Treatment of Inflammatory Bowel Disease at ECCO 2025. Retrieved February 28, 2025, from https://www.globenewswire.com/news-release/2025/02/21/3030459/0/en/Ensho-Therapeutics-Announces-Presentation-of-Data-Highlighting-NSHO-101-as-a-Once-Daily-Oral-Agent-for-the-Potential-Treatment-of-Inflammatory-Bowel-Disease-at-ECCO-2025.html [20] Immunic's Oral IMU-856 Demonstrated Dose-Dependent Increase of GLP-1 in Celiac Disease Patients and Corresponding Effects in Preclinical Testing. Retrieved February 28, 2025, from https://www.prnewswire.com/news-releases/immunics-oral-imu-856-demonstrated-dose-dependent-increase-of-glp-1-in-celiac-disease-patients-and-corresponding-effects-in-preclinical-testing-302381158.html [21] Arialys Therapeutics Initiates MAD Cohorts Having Completed All Planned SAD Cohorts in a Phase 1 Study of ART5803 for the Treatment of Autoimmune Neuropsychiatric Disease. Retrieved February 28, 2025, from https://www.arialysrx.com/news/arialys-therapeutics-initiates-mad-cohorts-having-completed-all-planned-sad-cohorts-in-a-phase-1-study-of-art5803-for-the-treatment-of-autoimmune-neuropsychiatric-disease [22] Adcendo ApS Announces U.S. FDA Clearance of IND Application for Phase I Tiffany-01 Trial of ADCE-T02. Retrieved February 28, 2025, from https://www.prnewswire.com/news-releases/adcendo-aps-announces-us-fda-clearance-of-ind-application-for-phase-i-tiffany-01-trial-of-adce-t02-302384298.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床1期基因疗法临床结果疫苗信使RNA

2025-02-15

·正大天晴药业集团

彭博《商业周刊》专访谢其润：只有创新才能在全球医药竞争中立足

近日，中国生物制药（1177.HK）董事会主席谢其润获选“2024彭博《商业周刊》年度人物50”。2月14日，《商业周刊》发表了题为《中国生物制药董事会主席谢其润：只有创新才能在全球医药竞争中立足》的专访文章。以下为全文：中国生物制药凭借 103 款在研药物管线数量，位列全球药企第 15 位 2024年，中国生物制药获批 4 款1类创新药，是国内数量最多的企业全球生物制药行业正处于快速变革之中，机遇与挑战并存，其中，中国生物制药表现不俗。2024年，中国生物制药获批4款一类创新药，是国内数量最多的企业。同时，中国生物制药凭借103款在研药物管线数量，位列全球药企第15位。近日，中国生物制药董事会主席谢其润获选为《商业周刊》年度人物。 Q：您认为未来5-10年生物制药行业的关键突破点会在哪些方向？ 2025年，构建"AI+生物医药"双螺旋战略已经是所有大药企的焦点。中国生物制药的数字化转型始于2011年。经历了无数内外阻碍，我们较同行先一步在2018年全面建成覆盖集团各部门的数字神经网络，让每个销售、生产及研发决策都有数据智能的支持。如今，三大AI引擎正重塑医药未来：在研发端，多模态生物计算平台让新药发现周期压缩60%；生产端，在实现每秒百万级的分子模拟，AI驱动的蛋白质折叠预测精度突破95%大关的时代背景下，我们希望建立以数字技术重构的"未来药厂"，大幅提升效率，实现精准制药；在临床端，千万量级的真实世界数据正通过认知计算转化为个体化医疗方案。面对大模型掀起的认知革命，我们未来不仅会深度参与构建医疗垂直领域的国产大模型生态，更在数字生物学前沿开辟新战场——当算力与生命的边界逐渐消融，我们相信在未来5-10年，中国生物制药将全面投入AI，致力于发现和创造有巨大临床意义的新药，为患者带来福音。 Q：如何看待中国生物制药在国际市场上的定位与发展方向，怎样突破国际竞争壁垒？ “只有创新才能在全球医药竞争中立足。唯有依托创新，推出真正填补临床空缺的好药，我们才能实现企业的愿景。”谢其润表示，2025年，中国生物制药将迎来创新药全面主导业绩发展的重要里程碑。我们通过自主研发、收购整合等方式突破国际壁垒，实现跨国合作的新模式。在这个临床数据为王的时代，我们有多款产品的临床数据取得显著突破，公司已进入创新产品收获期，未来几年将有一批First-in-class（同类最先）和Best-in-class（同类最优）的创新药物陆续上市。例如，我们的原研创新药贝莫苏拜单抗联合安罗替尼和化疗作为广泛期小细胞肺癌（ES- SCLC）患者的一线治疗达到了历史上最长的无进展生存期（PFS）和总生存期（OS）；我们的TQC3721是国内研发进度最快的国产PDE3/4抑制剂（用于治疗中重度慢性阻塞性肺病），目前位于全球进度第二，IIa期临床数据显示其有同类最优的潜力；拉尼兰诺（泛PPAR激动剂）是全球第一个进入III期临床的口服治疗非酒精性脂肪性肝炎的药物，II期临床试验结果明显优于其他口服产品。这些成果都得益于我们拥有强大的自主研发能力。作为中国最大的处方药企业之一，我们已经积累了近30年的临床试验经验，拥有超过3000人的优秀研发和临床团队，每年都要开展上百项临床试验，这些都使得中国生物制药有能力去搭建全球多中心临床的中国中心。未来，在这个平台上，将汇聚包括中国在内的亚洲各国数十家最优质的医院和一批最权威的临床和研发专家，能够用最高效率、最低成本、最科学有效地获得全球认可的一线临床数据。我们始终坚信，人类的健康事业是没有国界的，也是最不应设置壁垒的领域。中国生物制药将充分发挥中国药企研发效率高、临床资源广的优势，产出更多在疗效和安全性上拥有国际一流竞争力的产品，打破国际壁垒。但我们也必须承认，中国生物医药企业想要拥有更大全球影响力依然面临着挑战。例如在与海外标准互认、规则衔接、ICH原则遵循、医药GMP要求一致性等方面存在困难。中国的龙头企业应当发挥更重要的作用，甚至成为不同国家药审机构之间交流和沟通的桥梁，而中国生物制药愿意成为这样的“先行先试者”。 Q：中国生物制药的企业社会责任是如何履行的？ESG工作在其中发挥着怎样的作用？ ESG既是引领，也是保障。引领，就是要指导我们到底要做什么与实现什么。2023年，中国生物制药制定与发布了“CARE”ESG策略，规划出以“疾病治疗、医药可及、共赢关系、环境友好”为核心的社会责任目标和路径。在此方针指引下，我们系统推动了包括“碳中和目标路径”“医药可及性策略”“员工股权激励机制”“负责任供应链建设”等多项管理实践，并取得了显著成效。同时，在救灾济困、乡村振兴、教育捐赠与普惠医疗等领域，也开展了大量的社会公益行动，积极回馈社会。保障，则是为企业的高质量可持续发展提供保障。在董事会、管理层至成员企业ESG体系的有效保障下，中国生物制药的非财务直接风险得以全面管控，国际化发展中所面临的新兴风险也得到了前瞻性的应对，企业可持续发展能力与竞争力得以持续提升。近年来，我们在ESG领域所取得的成果获得了各界相关方的认可，包括MSCI ESG评级连续两年获得A级评价，首次入选标普可持续发展全球年鉴等。对我而言，这既是各界伙伴给予的认可，更是集团坚持可持续发展道路的动力。未来，希望能与各方携手，共同为企业、社会与环境的和谐发展贡献力量。 Q：在接班成为中国生物制药董事会主席的过程中，有没有一些特别难忘的经历或挑战？三十载星河长卷，两代人丹心铸剑。中国生物制药三十多年的发展中，凝聚了两代人的心血与努力。作为改革开放后第一家进入中国投资的外商企业，正大集团是中国改革开放的见证者、参与者和获益者；上世纪90年代初，我的父母创立了正大制药集团，并于2000年，以“中国生物制药”在香港联交所上市。父母用了二十年的时间将中国生物制药打造成为中国最大的处方药企业。2015年，接力棒交到了我的手中。在我看来，两代人传承的是一种持续创新的精神，为中国乃至全球人类健康事业贡献力量。“健康科技，温暖更多生命”，这是我们的理念和动力源泉。今年是我接班的第十年，回想接任公司这些年来的成就和里程碑事件有很多，但最让我感到骄傲的是，成功地将公司从一家仿制药为主的中国龙头企业，全面转型为一家全链条创新的国际化领军药企，并连续6年跻身全球制药50强。十年磨砺，我们来自创新药的收入占比从2015年的11%逐年提升，并将在2025年实现创新药收入占比50%，正式完成创新驱动业绩增长阶段的目标。十年持之以恒的自我革新，我们成功构建起精简高效的组织架构，培育出创新高效的研发团队，打造出全面自动化的 “智慧工厂”，锤炼出攻坚克难的销售大军。回首过往，每一步都不易，但每一步都作数。首先，我做的工作是在董事会和公司高管层统一认知，坚定目标，全面投入创新药研发。虽然仿制药曾给企业带来过丰厚的回报，但我们必须跳出思维陷阱、打破模式惯性，坚持引入创新人才，坚持投入创新研发。其次，创新就是要为长远布局，拿出“十年磨一剑”的韧劲。最后，要真正实现创新转型，最终需要走向全球。 2018年我们上市的一类创新药安罗替尼，虽然在研发过程中遇到了很多技术难题，当时面对的市场竞争也非常激烈，但我们没有退缩，不断优化方案，在当时就投入研发费用超过十亿。如今，安罗替尼已经成功获批7个适应症，被誉为“国药之光”，填补了非小细胞肺癌、软组织肉瘤、甲状腺髓样癌等多个癌症治疗领域治疗方案的空白，在与贝莫苏拜单抗的联用中也获得了全球最长的无进展生存期记录，为无数癌症患者带来了生命希望。除了自主研发以外，我们与全球的创新药企、研发技术平台以及顶级科学家建立了广泛合作网络，搭建了siRNA、多抗、ADC、治疗性疫苗等前沿技术平台，引入了近20个极具潜力的创新药，不断丰富创新管线，打造国际研发体系，为中国生物制药确立了“In China for Global”和“In Global for Global”的战略发展策略，通过国际化布局真正将“世界新”和“中国新”统一起来。内容来源：彭博《商业周刊》 ● 向世界发出中国药企的声音 | 谢承润在达沃斯接受媒体采访呼吁生物医药领域打破人为壁垒搭建合作桥梁 ● 正大天晴国内率先完成等效性研究，乌美溴铵维兰特罗吸入粉雾剂上市申请获受理 ● 两地四厂共谱蛇年新篇章，正大天晴2025年开工庆典圆满举行 ● 国产首创突破！妥洛特罗贴剂（德瑞妥）获批上市，守护全年龄段呼吸疾病患者健康

并购申请上市

2025-02-01

·GlobeNewswire-Health Care

Inventiva announces the publication of the results from the investigator-initiated proof-of-concept clinical trial evaluating lanifibranor in patients with T2D and MASLD in the Journal of Hepatology

As previously reported1, the study met the primary efficacy endpoint for the treatment with lanifibranor 800mg demonstrating a 44% reduction of hepatic fat measured by proton magnetic resonance spectroscopy (1H-MRS) following 24 weeks of treatment in patients with MASLD and T2D A significantly higher proportion of patients achieved a greater than 30% liver triglyceride reduction as well as MASLD resolution with lanifibranor compared to placebo Lanifibranor treatment significantly improved both hepatic and peripheral insulin sensitivity (i.e. fasting plasma insulin, fasting hepatic glucose production, hepatic insulin resistance index, insulin-stimulated muscle glucose disposal), which translated into better glycemic control (i.e. HbA1c) The study met multiple secondary metabolic endpoints confirming the cardiometabolic benefit of lanifibranor in patients with MASLD, and ability to improve adipose tissue function The study confirmed the favorable safety and tolerability profile of lanifibranor January 29, 2025 – Inventiva (Euronext Paris and Nasdaq: IVA) (“Inventiva” or the “Company”), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”) and other diseases with significant unmet medical needs, today announced the publication in Journal of Hepatology, a peer-reviewed scientific journal, of the results from the investigator-initiated clinical study led by Dr. Kenneth Cusi evaluating lanifibranor in patients with type 2 diabetes (“T2D”) and Metabolic dysfunction-Associated Liver Disease (“MASLD”)1. The clinical trial demonstrated significant improvement of hepatic, muscle and adipose tissue insulin resistance in patients with MASLD and T2D treated with lanifibranor. The proof-of-concept trial evaluating lanifibranor (800mg/day for 24 weeks) in 38 patients with MASLD and T2D achieved its primary efficacy endpoint. Patients that received treatment with lanifibranor achieved a 44% reduction in intrahepatic triglycerides (IHTG) measured using proton magnetic resonance spectroscopy (1H-MRS), significantly outperforming the placebo group (12%). The treatment with lanifibranor also resulted in a higher proportion of patients achieving over 30% liver triglyceride reduction (65% vs. 22%) and MASLD resolution (25% vs. 0%). Secondary endpoints showed improvements in glycemic control, lipid profiles, hepatic insulin sensitivity, muscle glucose disposal, and adipose tissue function. Lanifibranor was well tolerated with no safety concerns reported. These findings are consistent with those reported in previous trials with lanifibranor and highlight lanifibranor's potential for managing MASLD, T2D, and related metabolic conditions. Dr. Kenneth Cusi, Professor of Medicine at the Division of Endocrinology, Diabetes and Metabolism in the Department of Medicine, University of Florida and Principal Investigator of the study, stated: “This study highlights the promising potential with lanifibranor, an insulin-sensitizer that has already shown positive effects in patients with MASH. Within just 24 weeks of treatment, we observed significant improvements in hepatic fat, liver and muscle insulin sensitivity, and fat metabolism, reinforcing the strength of lanifibranor's mechanism of action. These results not only offer hope for managing patients with MASH but also bring crucial insights for patients with T2D and MASH—which we know is a patient population at higher risk of faster progression to advanced fibrotic stages.” Dr. Michael Cooreman, Chief Medical Officer of Inventiva: “We are very happy to see the results of this important clinical study published in the renowned Journal of Hepatology. By demonstrating the effect of lanifibranor on intrahepatic triglycerides reduction and MASLD resolution in patients with type-2 diabetes, this study complements the robust dataset from our Phase IIb NATIVE and Proof-of-Concept LEGEND studies, confirming the potential of lanifibranor as an effective candidate to address the needs of patients suffering from MASH and MASLD. We take this opportunity to express our gratitude and thanks to all patients and investigators, and to Dr. Cusi for successfully leading this study.” Publication details Publication title: “Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with type 2 diabetes and MASLD.” Authors: Diana Barb, Srilaxmi Kalavalapalli, Eddison Godinez Leiva, Fernando Bril, Philippe Huot-Marchand, Lucile Dzen, Jens T Rosenberg, Jean-Louis Junien, Pierre Broqua, Andrea Ortiz Rocha, Romina Lomonaco, Jean Louis Abitbol, Michael P Cooreman, Kenneth Cusi. Online version: doi: 10.1016/j.jhep.2024.12.045. Epub ahead of print. PMID: 39824443. Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce antifibrotic, anti-inflammatory and beneficial vascular and metabolic changes in the body by activating all three peroxisome proliferator-activated receptor (“PPAR”) isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPARδ, and a partial activation of PPARγ. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development for the treatment of MASH. Inventiva believes that lanifibranor’s moderate and balanced pan-PPAR binding profile contributes to the favorable tolerability profile that has been observed in clinical trials and pre-clinical studies to date. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor for the treatment of MASH. Inventiva is a clinical-stage biopharmaceutical company focused on the research and development of oral small molecule therapies for the treatment of patients with MASH and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the field of compounds targeting nuclear receptors, transcription factors and epigenetic modulation. Inventiva is currently advancing one clinical candidate, has a pipeline of two preclinical programs and continues to explore other development opportunities to add to its pipeline. Inventiva’s lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with MASH, a common and progressive chronic liver disease. Inventiva’s pipeline also includes odiparcil, a drug candidate for the treatment of adult MPS VI patients. As part of Inventiva’s decision to focus clinical efforts on the development of lanifibranor, it suspended its clinical efforts relating to odiparcil and is reviewing available options with respect to its potential further development. Inventiva is also in the process of selecting a candidate for its Hippo signaling pathway program. The Company has a scientific team of approximately 90 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, and clinical development. It owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly owned research and development facility. Inventiva is a public company listed on compartment B of the regulated market of Euronext Paris (ticker: IVA, ISIN: FR0013233012) and on the Nasdaq Global Market in the United States (ticker: IVA). www.inventivapharma.com The content above comes from the network. if any infringement, please contact us to modify.

临床结果快速通道突破性疗法

100 项与拉尼兰诺相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14801

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
非酒精性脂肪性肝炎	临床3期	捷克	正大天晴药业集团股份有限公司	2021-08-19
非酒精性脂肪性肝炎	临床3期	澳大利亚	正大天晴药业集团股份有限公司	2021-08-19
非酒精性脂肪性肝炎	临床3期	捷克	Inventiva SA	2021-08-19
非酒精性脂肪性肝炎	临床3期	葡萄牙	Delpharm Reims SAS	2021-08-19
非酒精性脂肪性肝炎	临床3期	以色列	Inventiva SA	2021-08-19
非酒精性脂肪性肝炎	临床3期	比利时	正大天晴药业集团股份有限公司	2021-08-19
非酒精性脂肪性肝炎	临床3期	意大利	正大天晴药业集团股份有限公司	2021-08-19
非酒精性脂肪性肝炎	临床3期	智利	Delpharm Reims SAS	2021-08-19
非酒精性脂肪性肝炎	临床3期	法国	Inventiva SA	2021-08-19
非酒精性脂肪性肝炎	临床3期	南非	Delpharm Reims SAS	2021-08-19

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临床结果

适应症

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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


NCT03459079 (NATIVE trial, CTgov)	临床2期	2型糖尿病 \| 代谢功能障碍相关的脂肪肝病	128	Lanifibranor (Lanifibranor Arm)	願範蓋壓壓襯製廠蓋獵(醖壓蓋餘繭遞淵齋觸憲) = 觸齋製獵築鏇鹹獵遞遞壓餘願糧構膚壓壓壓觸 (蓋齋鹹憲選餘選衊願願, 糧憲築膚淵醖壓膚糧築 ~ 膚網餘積製壓廠齋鏇夢) 更多	-	2024-09-19
				Placebo (Placebo)	願範蓋壓壓襯製廠蓋獵(醖壓蓋餘繭遞淵齋觸憲) = 顧範蓋簾齋鑰夢範顧醖壓餘願糧構膚壓壓壓觸 (蓋齋鹹憲選餘選衊願願, 遞網範廠蓋艱鹹築遞鑰 ~ 齋餘製淵積範齋襯壓鹹) 更多
NCT03008070 (NATIVE, Pubmed) 人工标引	临床2期	非酒精性脂肪性肝炎 insulin \| HOMA-IR \| HbA1c ... 更多	-	Lanifibranor	(觸鑰壓壓鏇蓋齋觸網餘) = 廠糧範積鏇壓範醖獵糧範艱艱醖獵鹹齋遞構蓋 (網齋糧觸憲壓繭製窪壓 ) 更多	积极	2024-05-10
NCT05232071 (LEGEND, GlobeNewswire) 人工标引	临床2期	2型糖尿病 \| 非酒精性脂肪性肝炎	63	lanifibranor+empagliflozin	(鏇築製廠衊範鏇衊窪觸) = 構憲艱築願積繭鏇觸簾醖鹹壓糧鑰壓選鏇遞廠 (蓋鹹鹽網遞觸齋糧鬱膚 ) 达到更多	积极	2024-03-18
				lanifibranor	(鏇築製廠衊範鏇衊窪觸) = 鑰簾淵築蓋鹽積廠鑰簾醖鹹壓糧鑰壓選鏇遞廠 (蓋鹹鹽網遞觸齋糧鬱膚 ) 达到更多
NCT03459079 (NATIVE trial, NASH_TAG2024)	临床2期	2型糖尿病 \| 代谢功能障碍相关的脂肪肝病 HbA1c \| plasma HDL-C \| adiponectin	38	Lanifibranor 800 mg	範蓋窪網衊鏇鬱夢廠壓(廠繭遞鹹艱網網壓餘鹽) = 構廠網醖蓋襯選糧觸憲齋築窪築鹹積艱餘範鑰 (膚窪憲鹹積蓋範壓製膚 ) 更多	积极	2024-01-04
				Placebo	範蓋窪網衊鏇鬱夢廠壓(廠繭遞鹹艱網網壓餘鹽) = 衊壓膚蓋餘夢醖觸廠蓋齋築窪築鹹積艱餘範鑰 (膚窪憲鹹積蓋範壓製膚 )
NASH_TAG2024	N/A	-	-	Semaglutide 0.06mg/kg	觸艱窪鏇蓋鹽齋簾鹹齋(壓觸糧鹽鑰遞鑰鹹夢網) = SEMA significantly reduced fructose and alcohol intake during the 5-week treatment when alcohol was provided, and LANI significantly reduced fructose and alcohol intake when alcohol was provided 壓簾獵選願鬱製鹽鹽衊 (醖淵鏇夢餘廠簾選築糧 ) 更多	-	2024-01-04
				Lanifibranor 30mg/kg
AASLD2023	N/A	-	-	Semaglutide	(顧淵簾願願獵願齋選築) = The 5-year OS rates were not significantly different between group B and group A 鹹齋鏇鏇鑰鹹齋淵鑰顧 (構鑰艱範網獵積蓋觸鏇 ) 更多	-	2023-11-10
				Lanifibranor
NCT03008070 (phase 2b, Pubmed \| N Engl J Med)	临床2期	非酒精性脂肪性肝炎	247	Lanifibranor 1200 mg	壓襯願鬱醖齋構遞鑰襯(廠選繭顧積廠鹽願夢壓) = 積醖構窪醖獵艱築製憲鹽蓋衊醖鹹遞膚構襯餘 (築積糧糧顧蓋築製繭廠 ) 更多	积极	2021-10-21
				Lanifibranor 800 mg	壓襯願鬱醖齋構遞鑰襯(廠選繭顧積廠鹽願夢壓) = 膚膚構願鹽鏇膚簾鹹蓋鹽蓋衊醖鹹遞膚構襯餘 (築積糧糧顧蓋築製繭廠 ) 更多
NCT03008070 (NATIVE \| phase 2b, CTgov)	临床2期	非酒精性脂肪性肝炎	247	IVA337 (IVA337 1200mg)	觸遞蓋構遞積衊膚繭獵(醖範蓋鬱獵範膚壓蓋齋) = 鏇憲構鹽齋鏇選範衊淵廠鏇糧憲糧觸選觸糧鹽 (鏇遞鑰鏇觸構獵窪積壓, 繭淵積蓋夢繭範醖鏇繭 ~ 淵製繭獵鹽繭製夢鏇範) 更多	-	2021-04-12
				IVA337 (IVA337 800mg)	觸遞蓋構遞積衊膚繭獵(醖範蓋鬱獵範膚壓蓋齋) = 膚淵窪網襯襯廠壓淵鹹廠鏇糧憲糧觸選觸糧鹽 (鏇遞鑰鏇觸構獵窪積壓, 鬱餘淵獵憲壓鹽膚繭淵 ~ 鹹憲襯遞糧繭獵構膚鹽) 更多
NCT03008070 (NATIVE, NASH_TAG2021)	临床2期	非酒精性脂肪性肝炎	-	Lanifibranor 30 mg/kg	(繭鹹網鏇簾憲繭蓋鹽糧) = Lanifibranor treatment demonstrated â¥2 point significant improvement in NAS 憲艱艱製鹽願夢鬱鑰膚 (憲糧簾憲觸選鏇齋鑰積 ) 更多	积极	2021-03-12