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) AGVifor 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

分子式C21H21FN6O2

InChIKeyKNYVRFXIVWUGBZ-UHFFFAOYSA-N

CAS号2095668-10-1

关联

6

项与 Vamifeport hydrochloride 相关的临床试验

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

NCT04938635 / Withdrawn临床2期

A Phase 2b, Double-blind, Randomised, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of VIT-2763 Multiple Doses in Adults With Transfusion-dependent Beta-thalassaemia

The main purpose of this study is to evaluate the efficacy of 3 multiple doses of VIT-2763 as measured by the reduction in red blood cell (RBC) transfusion burden from Week 13 to Week 24, to identify the most efficacious and safe dose.

开始日期2021-09-20

申办/合作机构

Vifor (International) AG

[+1]

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

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2021-06-18

申办/合作机构

Vifor (International) AG

[+1]

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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13

项与 Vamifeport hydrochloride 相关的文献（医药）

2024-09-01·HemaSphere

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

Article

作者: Altermatt, Patrick ; Flace, Anna ; Nyffenegger, Naja ; 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.

2022-08-18·Blood

The oral ferroportin inhibitor vamifeport improves hemodynamics in a mouse model of sickle cell disease

Article

作者: Doucerain, Cédric ; Flace, Anna ; Dürrenberger, Franz ; Buehler, Paul W. ; Nyffenegger, Naja ; Zennadi, Rahima ; Ingoglia, Giada ; Kalleda, Natarajaswamy ; Manolova, Vania ; Buzzi, Raphael M. ; Schaer, Dominik J.

AbstractSickle cell disease (SCD) is an inherited hemolytic anemia caused by a single point mutation in the β-globin gene of hemoglobin that leads to synthesis of sickle hemoglobin (HbS) in red blood cells (RBCs). HbS polymerizes in hypoxic conditions, leading to intravascular hemolysis, release of free hemoglobin and heme, and increased adhesion of blood cells to the endothelial vasculature, which causes painful vaso-occlusion and organ damage. HbS polymerization kinetics are strongly dependent on the intracellular HbS concentration; a relatively small reduction in cellular HbS concentration may prevent HbS polymerization and its sequelae. We hypothesized that iron restriction via blocking ferroportin, the unique iron transporter in mammals, might reduce HbS concentration in RBCs, thereby decreasing hemolysis, improving blood flow, and preventing vaso-occlusive events. Indeed, vamifeport (also known as VIT-2763), a clinical-stage oral ferroportin inhibitor, reduced hemolysis markers in the Townes model of SCD. The RBC indices of vamifeport-treated male and female Townes mice exhibited changes attributable to iron-restricted erythropoiesis: decreased corpuscular hemoglobin concentration mean and mean corpuscular volume, as well as increased hypochromic and microcytic RBC fractions. Furthermore, vamifeport reduced plasma soluble VCAM-1 concentrations, which suggests lowered vascular inflammation. Accordingly, intravital video microscopy of fluorescently labeled blood cells in the microvasculature of Townes mice treated with vamifeport revealed diminished adhesion to the endothelium and improved hemodynamics. These preclinical data provide a strong proof-of-concept for vamifeport in the Townes model of SCD and support further development of this compound as a potential novel therapy in SCD.

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	药物发现	希腊	Vifor (International) AG	2020-06-11
β地中海贫血	药物发现	以色列	Vifor (International) AG	2020-06-11
β地中海贫血	药物发现	泰国	Vifor (International) AG	2020-06-11
β地中海贫血	药物发现	黎巴嫩	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
β地中海贫血	药物发现	以色列	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
β地中海贫血	药物发现	泰国	Vifor (International) AG	2020-06-11
β地中海贫血	药物发现	黎巴嫩	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


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	廠繭齋衊築鹹願壓夢壓(壓繭醖襯鏇鑰簾網蓋廠) = 網鏇顧鏇淵鏇壓積鏇範糧鏇壓膚簾繭網範鹽繭 (廠願夢顧艱餘鏇顧繭選, 鏇繭醖鑰築繭簾獵鏇觸 ~ 鹹積衊糧範齋鹽淵夢鏇) 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)	(鑰鏇遞積衊夢構窪糧齋) = 蓋憲憲鑰選簾鹽構膚選選醖鑰壓網簾遞醖窪獵 (鬱築蓋網鑰鬱願網鹹觸 ) 更多	积极	2022-05-12
NCT04364269 (EHA2022) 人工标引	临床2期	输血依赖性β地中海贫血	25	Vamifeport hydrochloride (BID)	(膚獵膚壓蓋願築遞鹽選) = 構鬱鬱繭構衊艱蓋夢鬱壓淵鹹蓋遞鏇壓窪構簾 (網鏇廠壓範鏇鏇網範鏇 ) 更多	积极	2022-05-12