罗沙司他(Roxadustat) - 药物靶点：HIF-PHs_在研适应症：贫血，肾性贫血，慢性肾性贫血_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Roxadustat (JAN/USAN/INN)、可博美、ASP 1517

+ [9]

靶点

HIF-PHs

作用机制

HIF-PHs抑制剂(缺氧诱导因子脯氨酰羟化酶家族抑制剂)

治疗领域

血液及淋巴系统疾病泌尿生殖系统疾病

在研适应症

贫血肾性贫血慢性肾性贫血+ [2]

非在研适应症

伴随慢性肾病的贫血镰状细胞血症肿瘤+ [1]

原研机构

FibroGen, Inc.

在研机构

珐博进（中国）医药技术开发有限公司Astellas Pharma Europe Ltd.Astellas Pharma Global Development, Inc.

+ [5]

非在研机构

Astellas Pharma Europe BV

最高研发阶段批准上市

首次获批日期

中国 (2018-12-17),

慢性肾性贫血

最高研发阶段(中国)批准上市

特殊审评特殊审批 (中国)

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结构

分子式C19H16N2O5

InChIKeyYOZBGTLTNGAVFU-UHFFFAOYSA-N

CAS号808118-40-3

关联

136

项与罗沙司他相关的临床试验

LBCTR2024015495 / Suspended临床3期

A Phase 3, Open-label, Uncontrolled Study to Evaluate the Activity, Safety, Pharmacokinetics and Pharmacodynamics of Roxadustat for the Treatment of Anemia in Pediatric Participants with Chronic Kidney Disease - -

开始日期2024-06-01

申办/合作机构

Astellas Pharma US, Inc.

ACTRN12624000188538 / Not yet recruiting临床2期

Hypoxic Enhancement Before Major Surgery (HYPE): A pilot randomised controlled trial of preoperative Roxadustat vs placebo in patients undergoing major surgery, assessing safety, effectiveness and feasibility.

开始日期2024-04-15

申办/合作机构-

CTR20240386 / Active, not recruitingN/A

罗沙司他胶囊单中心、随机、开放、单剂量、两制剂、两周期、两序列交叉设计，空腹和餐后状态下的人体生物等效性研究。

本试验旨在研究单次空腹和餐后口服安徽省先锋制药有限公司研制、生产的罗沙司他胶囊（50 mg）的药代动力学特征；以珐博进（中国）医药技术开发有限公司生产的罗沙司他胶囊（爱瑞卓®，50 mg）为参比制剂，比较两制剂中药动学参数Cmax、AUC0-t、AUC0-∞，评价两制剂的人体生物等效性。

开始日期2024-02-29

申办/合作机构

安徽省先锋制药有限公司

100 项与罗沙司他相关的临床结果

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100 项与罗沙司他相关的转化医学

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100 项与罗沙司他相关的专利（医药）

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370

项与罗沙司他相关的文献（医药）

2024-03-01·Journal of Hypertension

Hypoxia-inducible factor-prolyl hydroxylase inhibitor Roxadustat (FG-4592) reduces renal fibrosis in Dahl salt-sensitive rats

Article

作者: Naito, Yoshiro ; Masuyama, Tohru ; Yasumura, Seiki ; Tsujino, Takeshi ; Ishihara, Masaharu ; Okuno, Keisuke ; Asakura, Masanori

Objective::

Although hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed for the treatment of renal anemia, their effects on cardiac and renal dysfunction remain unknown. We previously reported on Dahl salt-sensitive rats, in a rat model of salt-sensitive hypertension, that exhibited anemia and impaired expression of duodenal iron transporters after the development of hypertensive cardiac and renal dysfunction. Therefore, we investigated the effects of Roxadustat (FG-4592), an HIF-PH inhibitor, on anemia, iron regulation, and cardiac and renal dysfunction in Dahl salt-sensitive rats.

Methods::

Six-week-old male Dahl salt-sensitive rats were fed a normal or high-salt diet for 8 weeks. A further subset of Dahl salt-sensitive rats, that were fed a high-salt diet, was administered Roxadustat for 8 weeks.

Results::

Dahl salt-sensitive rats fed a high-salt diet developed hypertension, cardiac and renal dysfunction, and anemia after 8 weeks of feeding. Roxadustat increased hemoglobin and serum erythropoietin levels in Dahl salt-sensitive rats fed a high-salt diet. With regard to the iron-regulating system, Roxadustat lowered hepatic hepcidin gene expression and increased the gene expression of duodenal iron transporters, such as cytochrome b and divalent metal transporter 1, in Dahl salt-sensitive rats fed a high-salt diet. Roxadustat did not affect the development of hypertension and cardiac hypertrophy in Dahl salt-sensitive rats with a high-salt diet; however, Roxadustat treatment attenuated renal fibrosis in these rats.

Conclusions::

Roxadustat ameliorated anemia with affecting the gene expression of the iron-regulating system, and did not affect cardiac hypertrophy but attenuated renal fibrosis in Dahl salt-sensitive rats fed a high-salt diet.

International Urology and Nephrology

A clinical study on roxadustat for anemia in diabetic nephropathy: a 8-week study

Article

作者: Sun, Dong ; Raj, Ashok ; Zheng, Zhifang ; Jia, Ruoyu ; Xu, Yizhou ; Jiang, Luhua ; Zhang, Xuejie

PURPOSE:

The development of roxadustat is a standard treatment for renal anemia, and multiple clinical trials have proved its safety and efficacy. However, less information is available from trials of the population with diabetic nephropathy (DN). This study aimed to determine whether roxadustat is effective for treating DN.

METHODS:

This was a single-center, retrospective, institutional review board-approved cohort study. The patients with DN were chosen and given roxadustat or erythropoietin (EPO) for 8 weeks. The mean hemoglobin (Hb) level after 8 weeks of treatment served as the primary outcome. Alterations in the iron index and lipid levels were considered secondary objectives. Sub-group analysis was performed to observe the impact of inflammation and glycemic status on Hb.

RESULTS:

A total of 80 patients were enrolled, 40 in each group. After 8 weeks of treatment, the Hb levels in the roxadustat group were higher than those in the control group. The number of patients who achieved Hb response was higher in the roxadustat group than in the control group (77.5% versus 27.5%; P < 0.001). In addition to lowering total cholesterol and low-density lipoprotein cholesterol, roxadustat decreased ferritin and elevated total iron-binding capacity. Compared to the control group, roxadustat was more beneficial for patients with an inflammatory condition and poor glycemic control.

CONCLUSIONS:

Roxadustat treatment remarkably corrected anemia in patients with DN, and its effectiveness was unaffected by inflammation or glycemic control levels. In addition, roxadustat can also reduce a patient's blood lipid level and enhance the body's use of iron.

CLINICAL TRIAL REGISTRATION:

ChiCTR2200057232.

2024-03-01·Pediatric Nephrology

Compassionate use of roxadustat for treatment of refractory renal anemia in an infant

Article

作者: Liu, Dengli ; Chen, Yan ; Bai, Haitao ; He, Bizi ; Yang, Yang ; Yang, Yan

Abstract:

Background:

Erythropoiesis-stimulating agents (ESAs) have played an important role in the treatment of renal anemia in children, but cannot improve hemoglobin to target level in some cases. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, can stimulate endogenous erythropoietin production and regulate iron metabolism even in patients with kidney failure. However, roxadustat has not yet been approved for use in children.

Case–diagnosis/Treatment:

We report a case of refractory renal anemia in an 80-day-old boy, who was hyporesponsive to ESAs even in combination with iron supplementation and transfusion. Compassionate use of roxadustat successfully corrected the intractable anemia. Hyperkalemia is a manageable adverse event of concern during follow-up.

Conclusion:

The successful experience in this case may inform the clinical utility of roxadustat for refractory renal anemia in children, which should be further confirmed by well-designed prospective clinical trials.

264

项与罗沙司他相关的新闻（医药）

2024-04-24

·BioSpace

FibroGen Announces Clinical Data from Dose Escalation Phase 1b Study of FG-3246 (FOR46) in Combination with Enzalutamide in Patients with Metastatic Castration Resistant Prostate Cancer will be Presented at the 2024 ASCO Annual Meeting

SAN FRANCISCO, April 24, 2024 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ: FGEN) today announced that clinical data from the dose escalation portion of the Phase 1b/2 study of FG-3246 in combination with enzalutamide in patients with metastatic castration resistant prostate cancer have been selected for a poster presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 31-June 4, 2024 in Chicago, Illinois. Details for the poster presentation are as follows: Session: Poster Session – Genitourinary Cancer – Prostate, Testicular, and Penile Title: A Phase 1b dose escalation study of FOR46, a novel antibody-drug conjugate targeting a tumor-specific epitope of CD46, in combination with enzalutamide (Enza) in patients with metastatic castration resistant prostate cancer (mCRPC). Presenter: Nonna Shakhnazaryan and Dr. Rahul Aggarwal, MD from the UCSF Helen Diller Family Comprehensive Cancer Center Abstract number: 5066 Poster number: 472 Date and Time: June 2, 2024 at 9:00-12:00 AM CDT About FG-3246 FG-3246 (also known as FOR46) is a potential first-in-class fully human antibody-drug conjugate (ADC), exclusively in-licensed from Fortis Therapeutics, and is being developed by FibroGen for metastatic castration-resistant prostate cancer and other tumor types. FG-3246 binds to a tumor-specific epitope of CD46, a cell receptor target, that induces internalization upon antibody binding, is present at high levels in prostate cancer and other tumor types, and demonstrates limited expression in most normal tissues. FG-3246 is comprised of an anti-CD46 antibody, YS5, linked to the anti-mitotic agent, MMAE, which is a clinically and commercially validated ADC payload. FG-3246 has demonstrated anti-tumor activity in both preclinical and clinical studies. FG-3246 is currently in an ongoing investigator-initiated Phase 1b/2 study being conducted at UCSF to evaluate it in combination with enzalutamide with initial data expected in mid-2024, and a biomarker trial using a PET biomarker for CD46 using the same antibody backbone. We anticipate the initiation of a Phase 2 monotherapy dose optimization study of FG-3246 in metastatic castration-resistant prostate cancer in 2H 2024. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority. About FibroGen FibroGen, Inc. is a biopharmaceutical company focused on accelerating the development of novel therapies at the frontiers of cancer biology. Pamrevlumab, a fully human anti-CTGF monoclonal antibody, is in clinical development for the treatment of metastatic pancreatic cancer and locally advanced unresectable pancreatic cancer (LAPC). Roxadustat (爱瑞卓®, EVRENZOTM) is currently approved in China, Europe, Japan, and numerous other countries for the treatment of anemia in chronic kidney disease (CKD) patients on dialysis and not on dialysis. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted for review by the China Health Authority. FG-3246 (also known as FOR46), a first-in-class antibody-drug conjugate (ADC) targeting CD46 is in development for the treatment of metastatic castration-resistant prostate cancer. This program also includes the development of an associated CD46-targeted PET biomarker. In addition, FibroGen has expanded its research and development portfolio to include two immuno-oncology product candidates for the treatment of solid tumors. For more information, please visit FibroGen, Inc. Investors: David DeLucia, CFA Vice President of Corporate FP&A / Investor Relations ir@fibrogen.com Media: Meichiel Keenan Director, Investor Relations and Corporate Communications media@fibrogen.com

临床1期抗体药物偶联物ASCO会议上市批准

2024-04-19

·FiercePharma

FibroGen, former employees settle dispute over alleged trade secrets theft

Under a settlement, neither FibroGen nor China’s Andao Pharmaceutical or California-based Kind Pharmaceuticals are on the hook for any type of payment or compensation. Nearly a year and a half after FibroGen slapped a pair of former employees with a lawsuit alleging trade secrets theft, both the plaintiffs and the defendants are walking away from the case little worse for wear. China’s Andao Pharmaceutical and California-based Kind Pharmaceuticals, along with the latter company’s CEO and chief scientific officer, Dong Liu, Ph.D., and Shaojing Deng, Ph.D., this week announced a mutual agreement with FibroGen to withdraw legal proceedings in the trade secrets spat. Neither FibroGen nor Andao or Kind are on the hook for any type of payment or compensation, according to a press release issued by Kind. FibroGen originally sued Liu and Deng in December 2022 for allegedly pinching proprietary information and filing improper patents around hypoxia-inducible factor prolyl hydroxylase enzyme inhibitors (HIF-PHIs)—a class of drug used to treat anemia that includes FibroGen’s Astellas- and AstraZeneca-partnered roxadustat. Liu and Deng worked as scientists at FibroGen for years. In 2013, two years before leaving FibroGen, Liu founded Kind, according to a court order from last month. Deng joined Kind in a leadership position in 2019. Liu also founded Hangzhou Andao Pharmaceutical and became chairman, CEO and general manager of that company before formally exiting FibroGen, according to the court order, which granted and denied certain parts of the defendants' motion for dismissal. In its case, FibroGen said its former employees hatched an “international scheme” to give Kind an “unlawful head start” in order to avoid “years of research developing and identifying HIF-PHI compounds with clinical efficacy.” FibroGen originally sought to stop Kind from using its proprietary information and pressure the company to list FibroGen as the true owner on its HIF-PHI patents. FibroGen also wanted compensation and for its former employees to forfeit any profits made from patents they “wrongfully” claimed. With the new settlement in place, Kind Pharma is now “free to develop” its lead HIF-PHI candidate AND017 and other similar drugs in its pipeline, Kind explained in its press release. AND017 is in midphase testing in anemia and cancer-related anemia, according to Kind’s online pipeline. "Kind is pleased that these disputes have been fully and finally resolved,” Liu said in a statement. “With these disputes behind us, Kind can now focus on advancing its innovative pipeline of products to the market.” As for FibroGen’s roxadustat, the drug has fallen victim to a string of setbacks in the U.S. that culminated in late February with AstraZeneca returning the rights to FibroGen for the HIF-PHI in a range of territories outside China and South Korea, where it’s approved under the brand name Evrenzo. The decision came on the heels of a phase 3 trial flop and an FDA complete response letter for roxadustat in anemia associated with chronic kidney disease in the U.S. Outside China and Korea, Astellas has a deal with FibroGen to market Evrenzo in Japan and Europe.

临床3期高管变更专利侵权

2024-04-15

·米内网

【重磅】南京正大天晴拿下首仿，抢食默沙东$6亿畅销品种

精彩内容4月15日NMPA官网发布最新药品获批信息，南京正大天晴制药的来特莫韦片获批，为国内首仿。默沙东的来特莫韦2023年全球销售超过6亿美元，南京正大天晴制药是该品种首家报产的国内药企。图1：南京正大天晴制药最新获批的产品情况来源：NMPA官网来特莫韦是默沙东研发的抗病毒新药，用于接受异基因造血干细胞移植(HSCT)的巨细胞病毒(CMV)血清学阳性的成人受者[R＋]预防巨细胞病毒感染和巨细胞病毒病。原研的来特莫韦片在2021年获批进入中国市场，原研的来特莫韦注射液也在2022年获批进口，片剂和注射剂均在2022年进入国家医保谈判目录。图2：近几年来特莫韦的全球销售情况（单位：百万美元）来源：米内网跨国上市公司数据库米内网数据显示，默沙东的来特莫韦在2019年的全球销售额已突破1.65亿美元，近几年保持快速增长态势，2023年全球销售额已超过了6亿美元，市场潜力不容小觑。图3：来特莫韦相关产品的仿制上市申请情况来源：米内网中国申报进度（MED）数据库南京正大天晴制药在2022年首家提交了来特莫韦片和来特莫韦注射液的4类仿制上市申请，目前已拿下来特莫韦片的国内首仿，同时也是公司今年以来首个获批的新产品。表1：南京正大天晴制药报产在审的产品来源：米内网中国申报进度（MED）数据库目前，南京正大天晴制药有15个新产品报产在审。磷酸芦可替尼片、来特莫韦注射液、氯苯唑酸葡胺软胶囊、达格列净二甲双胍缓释片、罗沙司他胶囊、哌柏西利片、复方维生素C聚乙二醇(3350)钠钾散目前暂无国产仿制药获批，南京正大天晴制药有望争夺这7个产品的国内首仿。资料来源：NMPA官网、米内网数据库本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

上市批准专利侵权

100 项与罗沙司他相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10593	-	B03XA05	DB04847

研发状态

适应症	最高研发状态	国家/地区	公司
贫血	批准上市	智利更多	AstraZeneca PLC 更多
骨髓增生异常综合征	临床3期	中国更多	FibroGen, Inc. 更多
慢性肾病	临床3期	西班牙更多	Astellas Pharma Global Development, Inc. 更多
伴随慢性肾病的贫血	终止	美国更多	FibroGen, Inc. 更多
终末期肾脏病	无进展	罗马尼亚更多	FibroGen, Inc. 更多

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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


NCT04655027 (CTgov)	临床4期	伴随慢性肾病的贫血 \| 慢性肾性贫血	25	Roxadustat (Roxadustat)	憲膚顧鬱鏇醖繭積窪淵(壓艱壓糧廠築蓋膚遞築): Difference in Estimate (LSM) = 19.5 (95.0% CI, -11.155 ~ 50.15), P-Value = 0.212 更多	-	2024-04-22
				rHuEPO (rHuEPO)
Pubmed	临床3期	慢性肾病 hemoglobin level \| transferrin saturation	2,354	Roxadustat	糧製襯築壓獵繭願構夢(鬱壓觸夢鏇選襯鬱齋淵) = high hemoglobin rate of rise (≥ 0.5 g/dL/week; odds ratio [OR] 2.09; 95% confidence interval [CI] 0.98-4.46) showed a trend towards increased risk of thromboembolic events before week 12 淵獵願構蓋糧鹹鹹壓蓋 (範選構繭膚願餘餘鑰簾 ) 更多	-	2024-04-01
NCT03263091 (MATTERHORN, GlobeNewswire) 人工标引	临床3期	骨髓增生异常综合征	62	Roxadustat (higher transfusion burden)	衊淵網糧範餘積壓鑰製(鹽製窪醖鑰構醖廠鏇醖) = 廠積廠憲齋顧獵觸築構鹽鑰構窪積餘製鬱淵鬱 (鑰鹽淵衊鏇窪壓網蓋觸, 20.8 ~ 53.8) 更多	积极	2023-12-09
				placebo (higher transfusion burden)	衊淵網糧範餘積壓鑰製(鹽製窪醖鑰構醖廠鏇醖) = 壓壓製構衊鬱繭網築艱鹽鑰構窪積餘製鬱淵鬱 (鑰鹽淵衊鏇窪壓網蓋觸, 2.4 ~ 30.2) 更多
MATTERHORN (ASH2023)	临床3期	骨髓增生异常综合征	140	Roxadustat	繭淵齋鏇網網齋夢憲艱(構願顧餘窪廠衊積願繭) = percentages of pts with TEAEs leading to treatment discontinuation were similar across arms 壓繭製膚觸鹹鹽鑰廠鏇 (廠觸蓋膚繭衊齋膚鑰壓 ) 更多	积极	2023-12-09
				Placebo
ESMO2023 人工标引	临床3期	肿瘤	140	Roxadustat	選餘鹽餘遞齋網夢夢簾(鑰鹹範膚範齋願遞窪醖) = 網廠鹽廠觸範鏇鏇製獵選鏇鑰壓襯積齋範顧築 (繭選製膚築鏇憲窪艱鹹, 13.58 ~ 20.71)	非劣	2023-10-21
				rHuEPO-α	選餘鹽餘遞齋網夢夢簾(鑰鹹範膚範齋願遞窪醖) = 積艱醖蓋範鏇淵願夢醖選鏇鑰壓襯積齋範顧築 (繭選製膚築鏇憲窪艱鹹, 11.34 ~ 19.50)
ERA2023	N/A	甲状腺功能减退症	93	Roxadustat	衊餘網鑰遞壓醖襯顧繭(鹹鹹醖網製鹽遞廠顧構) = 積夢齋憲遞繭夢觸膚襯壓繭範齋襯鏇廠衊獵鏇 (衊鏇鏇獵衊醖鑰壓夢願 )	-	2023-06-15
DOLOMITES, 1517-CL-0610; HIMALAYAS, FGCL-4592-063; SIERRAS, FGCL-4592-064; ROCKIES, D5740C00002 (Pubmed)	临床3期	伴随慢性肾病的贫血	2,142	Roxadustat	齋廠簾網蓋構構蓋壓鬱(鏇壓淵鹹觸淵製顧壓膚): HR = 0.79 (95% CI, 0.61 ~ 1.02) 更多	积极	2023-02-07
				Erythropoiesis-Stimulating Agents
NCT04410198 (CTgov)	临床3期	终末期肾脏病 \| 贫血	203	Roxadustat	顧鬱鹹艱獵遞構選襯簾(網憲選廠鹽艱襯製糧遞) = 憲顧鏇簾蓋遞簾鬱構醖憲鹹網獵顧衊製顧窪選 (觸壓夢鏇鬱積廠遞糧夢, 顧繭觸築觸構繭壓鏇廠 ~ 蓋夢壓醖醖膚淵壓夢夢) 更多	-	2022-09-13
NCT04484857 (CTgov)	临床3期	终末期肾脏病 \| 贫血	283	Roxadustat	壓蓋構繭鹹廠鹽範願鏇(願繭襯壓製膚蓋獵顧膚) = 製艱膚夢鑰鏇壓網淵範窪鑰製醖選繭夢夢顧網 (鹽築襯蓋鹹齋壓糧築窪, 艱製鑰餘餘簾鏇遞鏇鏇 ~ 憲糧鏇艱膚簾蓋顧觸壓) 更多	-	2022-07-26
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