Vamifeport hydrochloride(Vamifeport hydrochloride) - 药物靶点：FPN1_在研适应症：β地中海贫血，全身性肉碱缺乏症，镰状细胞血症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Vamifeport

靶点

FPN1

作用方式

抑制剂

作用机制

FPN1抑制剂(膜铁转运蛋白-1抑制剂)

治疗领域

神经系统疾病心血管疾病遗传病与畸形+ [3]

在研适应症

β地中海贫血全身性肉碱缺乏症镰状细胞血症

非在研适应症

非输血依赖性地中海贫血输血依赖性β地中海贫血

原研机构

Vifor Pharma AG

在研机构

Vifor (International) AG

CSL Behring LLCVifor Fresenius Medical Care Renal Pharma France S.A.S.

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C21H21FN6O2

InChIKeyKNYVRFXIVWUGBZ-UHFFFAOYSA-N

CAS号2095668-10-1

关联

5

项与 Vamifeport hydrochloride 相关的临床试验

NCT06726863

/ Completed临床1期

A Phase 1, Randomized, Open-label Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Vamifeport After Multiple Oral Administration of One Immediate-release Formulation and After Single and Multiple Oral Administration of Two Prolonged-release Formulations in Healthy Adult Subjects

This is a phase 1, single-center, randomized, open-label study to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and safety of vamifeport after multiple oral administrations of one immediate-release (IR) formulation and after single and multiple oral administrations of two prolonged-release (PR) formulation in healthy adult participants.

开始日期2024-11-22

申办/合作机构

CSL Behring LLC

NCT04817670

/ Completed临床2期

A Phase 2a, Double-blind, Randomised, Placebo-controlled, Efficacy, and Safety Study of Multiple Doses of VIT-2763 in Subjects With Sickle Cell Disease (ViSionSerenity)

The purpose of this study is to investigate the effect of VIT-2763 on markers of hemolysis (breakdown in red blood cells) in sickle cell disease (SCD). The safety, tolerability and clinical beneficial effects of VIT-2763 for the treatment of SCD are also explored.

开始日期2021-11-18

申办/合作机构

Vifor (International) AG

[+1]

NCT05077436

/ Completed临床1期

A Randomised, Open-Label, Food Effect and Formulation Bioavailability Study of Two Vamifeport Oral Formulations in Healthy Male and Female Adults

Two different vamifeport oral formulations will be administered in fed and fasted state to assess the vamifeport food-drug interaction and to assess the relative bioavailability (the proportion of drug entering the circulation) of 2 different vamifeport oral formulations in healthy adult participants.
Participants will be randomly allocated to one of four treatment sequences, with four dosing periods each, where different combinations of both formulations will be administered following fasted and fed state.
The total study duration for each participant is up to 7 weeks and 4 days.

开始日期2021-10-14

申办/合作机构

Vifor (International) AG

100 项与 Vamifeport hydrochloride 相关的临床结果

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100 项与 Vamifeport hydrochloride 相关的转化医学

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100 项与 Vamifeport hydrochloride 相关的专利（医药）

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14

项与 Vamifeport hydrochloride 相关的文献（医药）

2025-01-09·Blood

Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical study

Article

作者: Manolova, Vania ; Dürrenberger, Franz ; Asperti, Michela ; Antypiuk, Ada ; Sharma, Richa ; Navaneethabalakrishan, Shobana ; Vance, S. Zebulon ; Vinchi, Francesca ; Passos, Sara

AbstractAlthough iron overload is a common feature in myelodysplastic syndromes (MDS), it remains unclear how iron excess is detrimental for disease pathophysiology. Taking advantage of complementary approaches, we analyzed the impact of iron overload and restriction achieved through genetic activation of ferroportin (FPN) via the C326S mutation (FPNC326S) and pharmacologic inhibition (vamifeport) of the iron exporter FPN, respectively, in a MDS mouse model. Although FPNC326S-induced iron overload did not significantly improve the late stages of erythroid maturation, vamifeport-mediated iron restriction ameliorated anemia and red blood cell maturation in MDS mice, through the reduction of oxidative stress and apoptosis in erythroid progenitors. Iron overload aggravated, and restriction alleviated, reactive oxygen species formation, DNA damage, and cell death in hematopoietic stem and progenitor cells (HSPCs), resulting in altered cell survival and quality. Finally, myeloid bias, indicated by expanded bone marrow myeloid progenitors and circulating immature myeloid blasts, was exacerbated by iron excess and attenuated by iron restriction. Overall, vamifeport treatment resulted in improved anemia and significant survival increment in MDS mice. Interestingly, the combined therapy with vamifeport and the erythroid maturation agent luspatercept has superior effect in improving anemia and myeloid bias as compared with single treatments and offers additive beneficial effects in MDS. Our results prove, to our knowledge, for the first time in a preclinical model, that iron plays a pathologic role in transfusion-independent MDS. This is likely aggravated by transfusional iron overload, as suggested by observations in the FPNC326SMDS model. Ultimately, the beneficial effects of pharmacologic FPN inhibition uncovers the therapeutic potential of early prevention of iron toxicity in transfusion-independent MDS.

2024-09-01·HemaSphere

The oral ferroportin inhibitor vamifeport prevents liver iron overload in a mouse model of hemochromatosis

Article

作者: Altermatt, Patrick ; Nyffenegger, Naja ; Flace, Anna ; Sundstrom, Hanna ; Manolova, Vania ; Varol, Ahmet ; Doucerain, Cédric ; Dürrenberger, Franz

AbstractHemochromatosis is an inherited iron overload condition caused by mutations that reduce the levels of the iron‐regulatory hormone hepcidin or its binding to ferroportin. The hepcidin–ferroportin axis is pivotal to iron homeostasis, providing opportunities for therapeutic intervention in iron overload disorders like hemochromatosis. The aim of this study was to evaluate the efficacy of the oral ferroportin inhibitor vamifeport in the Hfe C282Y mouse model, which carries the most common mutation found in patients with hemochromatosis. A single oral dose of vamifeport lowered serum iron levels in Hfe C282Y mice, with delayed onset and shorter duration than observed in wild‐type mice. Vamifeport induced transient hypoferremia by inhibiting ferroportin and resulted in a feedback regulation of liver Hamp in wild‐type mice, which was absent in Hfe C282Y mice, reflecting the dysregulated systemic iron sensing in this hemochromatosis model. Chronic dosing with vamifeport led to sustained serum and liver iron reductions in Hfe C282Y mice, as well as markedly reducing liver Hamp expression in Hfe C282Y mice, suggesting distinct regulation of liver Hamp expression following acute or continuous iron restriction via vamifeport. At the tested dose, vamifeport retained its activity when combined with phlebotomy and did not significantly interfere with liver iron removal by phlebotomy in Hfe C282Y mice. These data demonstrate that chronic vamifeport treatment significantly reduces serum iron levels and prevents liver iron loading in the Hfe C282Y mouse model of hemochromatosis, thus providing preclinical proof of concept for the efficacy of vamifeport in hemochromatosis with or without phlebotomy.

2023-10-01·Haematologica

Ferroportin inhibitor vamifeport ameliorates ineffective erythropoiesis in a mouse model of β-thalassemia with blood transfusions.

Article

作者: Altermatt, Patrick ; Nyffenegger, Naja ; Flace, Anna ; Dürrenberger, Franz ; Kalleda, Natarajaswamy ; Doucerain, Cédric ; Ingoglia, Giada ; Manolova, Vania

β-thalassemia is an inherited anemia characterized by ineffective erythropoiesis. Blood transfusions are required for survival in transfusion-dependent β-thalassemia and are also occasionally needed in patients with non-transfusion-dependent β-thalassemia. Patients with transfusion-dependent b-thalassemia often have elevated transferrin saturation (TSAT) and non-transferrin-bound iron (NTBI) levels, which can lead to organ iron overload, oxidative stress, and vascular damage. Vamifeport is an oral ferroportin inhibitor that was previously shown to ameliorate anemia, ineffective erythropoiesis, and dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia, under non-transfused conditions. Our study aimed to assess the effects of oral vamifeport on iron-related parameters (including plasma NTBI levels) and ineffective erythropoiesis following blood transfusions in Hbbth3/+ mice. A single dose of vamifeport prevented the transient transfusion-mediated NTBI increase in Hbbth3/+ mice. Compared with vehicle treatment, vamifeport significantly increased hemoglobin levels and red blood cell counts in transfused mice. Vamifeport treatment also significantly improved ineffective erythropoiesis in the spleens of Hbbth3/+ mice, with additive effects observed when treatment was combined with repeated transfusions. Vamifeport corrected leukocyte counts and significantly improved iron-related parameters (serum transferrin, TSAT and erythropoietin levels) versus vehicle treatment in Hbbth3/+ mice, irrespective of transfusion status. In summary, vamifeport prevented transfusion-mediated NTBI formation in Hbbth3/+ mice. When given alone or combined with blood transfusions, vamifeport also ameliorated anemia, ineffective erythropoiesis, and dysregulated iron homeostasis. Administering vamifeport together with repeated blood transfusions additively ameliorated anemia and ineffective erythropoiesis in this mouse model, providing preclinical proof-of-concept for the efficacy of combining vamifeport with blood transfusions in β-thalassemia.

100 项与 Vamifeport hydrochloride 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
β地中海贫血	临床2期	希腊	Vifor (International) AG	2020-06-11
β地中海贫血	临床2期	意大利	Vifor (International) AG	2020-06-11
β地中海贫血	临床2期	黎巴嫩	Vifor (International) AG	2020-06-11
β地中海贫血	药物发现	希腊	Vifor (International) AG	2020-06-11
β地中海贫血	药物发现	意大利	Vifor (International) AG	2020-06-11
非输血依赖性地中海贫血	药物发现	以色列	Vifor (International) AG	2020-06-11
非输血依赖性地中海贫血	药物发现	泰国	Vifor (International) AG	2020-06-11
非输血依赖性地中海贫血	药物发现	希腊	Vifor (International) AG	2020-06-11
非输血依赖性地中海贫血	药物发现	黎巴嫩	Vifor (International) AG	2020-06-11
非输血依赖性地中海贫血	药物发现	意大利	Vifor (International) AG	2020-06-11

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临床结果

适应症

分期

评价

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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


NCT04817670 (ViSionSerenity, CTgov)	临床2期	镰状细胞血症	25	VIT-2763 (Cohort 1: VIT-2763 60 mg BID (120 mg/Day))	鏇鏇窪憲鑰鑰觸獵顧鑰(網糧獵觸繭憲遞構膚夢) = 糧觸夢網醖製獵網廠願糧鑰憲淵簾憲製製築膚 (夢壓顧顧憲膚獵鹽網齋, 憲構壓範願齋鑰範遞獵 ~ 範廠構膚觸獵齋膚願窪) 更多	-	2025-02-18
				VIT-2763 (Cohort 2: VIT-2763 120 mg BID (240 mg/Day))	鏇鏇窪憲鑰鑰觸獵顧鑰(網糧獵觸繭憲遞構膚夢) = 遞憲觸鬱獵製鏇築積齋糧鑰憲淵簾憲製製築膚 (夢壓顧顧憲膚獵鹽網齋, 憲壓觸糧齋鹽網廠醖衊 ~ 遞夢窪鏇鏇齋醖憲鏇膚) 更多
NCT04364269 (VITHAL, CTgov)	临床2期	β地中海贫血 \| 非输血依赖性地中海贫血	35	Placebo	鏇艱選廠鏇餘壓襯壓鬱(衊築構齋憲網夢願膚鏇) = 醖醖遞網製積觸構繭築艱製顧蓋壓積簾網夢鹽 (範憲構鏇憲淵鹹鬱觸醖, 鏇網築積選鏇艱淵餘鬱 ~ 糧糧憲淵鏇鹹簾衊顧夢) 更多	-	2023-12-14
NCT04364269 (EHA2022) 人工标引	临床2期	输血依赖性β地中海贫血	25	Vamifeport hydrochloride (QD)	(憲製糧襯簾遞鹽淵艱廠) = 觸憲糧簾選願構廠構醖襯壓淵鹽齋構獵製鬱鏇 (鑰衊廠餘鬱鬱齋窪顧獵 ) 更多	积极	2022-05-12
				Vamifeport hydrochloride (BID)	(繭衊獵網廠壓衊鬱選簾) = 鬱範窪膚窪鬱餘鏇觸鑰築艱餘夢顧蓋襯醖網膚 (繭積鹽襯窪夢網鹹壓願 ) 更多