Delving into the Latest Updates on Vamifeport hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Vamifeport

Target

FPN1

Mechanism

FPN1 inhibitors(Ferroportin-1 inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesCongenital Disorders+ [3]

Active Indication

Beta-ThalassemiaSystemic Carnitine DeficiencyAnemia, Sickle Cell+ [1]

Inactive Indication

Iron OverloadNon-transfusion dependent thalassaemiaTransfusion-dependent Beta Thalassemia

Originator Organization

Vifor Pharma AG

Active Organization

Vifor (International) AG

Vifor Pharma AGVifor Fresenius Medical Care Renal Pharma France S.A.S.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Structure

Molecular FormulaC21H21FN6O2

InChIKeyKNYVRFXIVWUGBZ-UHFFFAOYSA-N

CAS Registry2095668-10-1

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.

Start Date14 Oct 2021

Sponsor / Collaborator

Vifor (International) AG

LBCTR2021064783 / SuspendedPhase 2

A Phase 2a, double-blind, randomised, placebo-controlled, ascending dose and maintenance dose, efficacy, and safety study of multiple doses of VIT-2763 in subjects with sickle cell disease

Start Date30 Sep 2021

Sponsor / Collaborator-

100 Clinical Results associated with Vamifeport hydrochloride

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100 Translational Medicine associated with Vamifeport hydrochloride

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100 Patents (Medical) associated with Vamifeport hydrochloride

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10

Literatures (Medical) associated with Vamifeport hydrochloride

01 Oct 2023·Haematologica

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

Article

Author: 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.

21 Mar 2023·eLife

Structures of ferroportin in complex with its specific inhibitor vamifeport.

Article

Author: Lehmann, Elena Farah ; Liziczai, Márton ; Langini, Cassiano ; Sundstrom, Hanna ; Manolova, Vania ; Altermatt, Patrick ; Dürrenberger, Franz ; Drożdżyk, Katarzyna ; Manatschal, Cristina ; Dutzler, Raimund

A central regulatory mechanism of iron homeostasis in humans involves ferroportin (FPN), the sole cellular iron exporter, and the peptide hormone hepcidin, which inhibits Fe²⁺ transport and induces internalization and degradation of FPN. Dysregulation of the FPN/hepcidin axis leads to diverse pathological conditions, and consequently, pharmacological compounds that inhibit FPN-mediated iron transport are of high clinical interest. Here, we describe the cryo-electron microscopy structures of human FPN in complex with synthetic nanobodies and vamifeport (VIT-2763), the first clinical-stage oral FPN inhibitor. Vamifeport competes with hepcidin for FPN binding and is currently in clinical development for β-thalassemia and sickle cell disease. The structures display two distinct conformations of FPN, representing outward-facing and occluded states of the transporter. The vamifeport site is located in the center of the protein, where the overlap with hepcidin interactions underlies the competitive relationship between the two molecules. The introduction of point mutations in the binding pocket of vamifeport reduces its affinity to FPN, emphasizing the relevance of the structural data. Together, our study reveals conformational rearrangements of FPN that are of potential relevance for transport, and it provides initial insight into the pharmacological targeting of this unique iron efflux transporter.

18 Aug 2022·Blood

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

Article

Author: Doucerain, Cédric ; Dürrenberger, Franz ; Flace, Anna ; 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 Deals associated with Vamifeport hydrochloride

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-transfusion dependent thalassaemia	Phase 3	GR	Vifor (International) AG	11 Jun 2020
Non-transfusion dependent thalassaemia	Phase 3	LB	Vifor (International) AG	11 Jun 2020
Non-transfusion dependent thalassaemia	Phase 3	IT	Vifor (International) AG	11 Jun 2020
Beta-Thalassemia	Phase 2	GR	Vifor (International) AG	11 Jun 2020
Beta-Thalassemia	Phase 2	GR	Vifor (International) AG	11 Jun 2020
Thalassemia	Phase 2	-	Vifor Pharma AG	-
Beta-Thalassemia	Preclinical	IT	Vifor (International) AG	11 Jun 2020
Non-transfusion dependent thalassaemia	Discovery	TH	Vifor (International) AG	11 Jun 2020
Non-transfusion dependent thalassaemia	Discovery	IL	Vifor (International) AG	11 Jun 2020
Iron Overload	Discovery	GR	Vifor Pharma AG	03 Mar 2020

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04364269 (EHA2022) Manual	Phase 2	Transfusion-dependent Beta Thalassemia	25	Vamifeport hydrochloride (QD)	(ggwfmbxtlp) = mjzznkmnys ykzkptsroz (vnbbmhrbfw ) View more	Positive	12 May 2022
NCT04364269 (EHA2022) Manual	Phase 2	Transfusion-dependent Beta Thalassemia	25	Vamifeport hydrochloride (BID)	(mpttyarclg) = tpiskauhro nnxruypzts (qdxpjnrolt ) View more	Positive	12 May 2022
NCT04364269 (CTgov)	Phase 2	Non-transfusion dependent thalassaemia \| Beta-Thalassemia	35	Placebo	(inyrnxfnly) = hhulkxfkas kknddqragu (fulpgpgjpe, rwuperjjfh - dbpszngkwc) View more	-	14 Dec 2023