Vifor Pharma receives positive phase-I trial results for oral ferroportin inhibitor
- Category: Small Molecules
- Published on Monday, 07 January 2019 12:02
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- Data in healthy volunteers shows favorable safety/tolerability profile
- Early results translate well from preclinical models to humans
- Phase-II study in beta-thalassemia patients to begin in the second half of 2019
GLATTBRUGG, Switzerland I January 7, 2019 I Vifor Pharma is pleased to report positive phase-I trial results for its oral ferroportin inhibitor. The trial which was conducted amongst healthy volunteers over a period of 9 months, concluded in October 2018. Trial subjects received single oral doses of VIT-2763 (ferroportin inhibitor) from 5 mg to 240 mg, or multiple doses from 60 mg to 120 mg once or twice daily over 7 days.
In all treated trial participants, the ferroportin inhibitor was well tolerated with mild to moderate side effects that were transient and self-limiting. The human pharmacokinetic profile exhibited dose-linear exposure, following which serum iron was lowered and remained below baseline values up to 24 hours post-dose. This iron-lowering pharmacodynamic effect is consistent with observations in preclinical models.
Following these positive phase-I results, Vifor Pharma intends to start a phase-II proof-of-concept trial in the second half of 2019. This will be a phase-II randomized, controlled, multi-national trial conducted in patients with beta-thalassemia and documented iron overload.
VIT-2763 is an oral inhibitor of ferroportin, the only known mammalian iron exporter and essential for transport of iron from one cell type to another. Preclinical models had already shown that VIT-2763 decreases serum iron levels in a dose-dependent manner1.
Beta-thalassemia is an inherited, rare blood disorder that reduces the production of functional haemoglobin in red blood cells, which can lead to a lack of oxygen in many parts of the body potentially causing anaemia. Affected individuals may experience classic signs of anaemia including fatigue, weakness and shortness of breath. Severe forms can cause serious, even life-threatening complications if left untreated. Beta-thalassemia is often treated with blood transfusions which may lead to excess levels of iron in the body (iron overload). Treatment with VIT-2763 can improve iron metabolism and the production of red blood cells, erythropoiesis.
Stefan Schulze, President of the Executive Committee and Chief Operating Officer of Vifor Pharma Group commented: “VIT-2763 has made a strong transition from the preclinical stage into human trials. These results are encouraging and provide a strong basis from which we can continue to build the ferroportin inhibitor programme. This is a novel orally administered therapy to treat diseases related to iron overload and it has the potential to transform the treatment of iron-related diseases.”
Vifor Pharma Group is a global pharmaceutical company. It aims to become the global leader in iron deficiency, nephrology and cardio-renal therapies. The company is the partner of choice for pharmaceuticals and innovative patient-focused solutions. Vifor Pharma Group strives to help patients around the world with severe and chronic diseases lead better, healthier lives. The company develops, manufactures and markets pharmaceutical products for precision patient care. Vifor Pharma Group holds a leading position in all its core business activities and consists of the following companies: Vifor Pharma; Vifor Fresenius Medical Care Renal Pharma, a joint company with Fresenius Medical Care; Relypsa; and OM Pharma. Vifor Pharma Group is headquartered in Switzerland, and listed on the Swiss Stock Exchange (SIX Swiss Exchange, VIFN, ISIN: CH0364749348). For more information, please visit www.viforpharma.com.
Vifor Pharma, a company of the Vifor Pharma Group, is a world leader in the discovery, development, manufacturing and marketing of pharmaceutical products for the treatment of iron deficiency. The company also offers a diversified portfolio of prescription and non-prescription medicines. Vifor Pharma’s operational headquarters are in Zurich, Switzerland, and the company has an increasingly global presence and a broad network of affiliates and partners around the world. For more information about Vifor Pharma, please visit www.viforpharma.com.
VIT-2763 is a first-in class oral inhibitor of ferroportin, the only known iron transporter in mammals playing a key role in regulating iron uptake and distribution in the body and thus in controlling iron levels in the blood. Developed by Vifor Pharma, VIT-2763 binds to ferroportin at the molecular level and blocks it to prevent iron from being released into the blood. In pre-clinical studies, VIT-2763 prevented iron loading, improved anaemia and ameliorated ineffective erythropoiesis and splenomegaly in a murine thalassaemia disease model. Thus, VIT-2763 exhibits potential for the same positive effects in patients suffering from ineffective erythropoiesis and iron overload conditions.1
Beta-thalassemia is a heterogeneous autosomal recessive hereditary anaemia characterized by reduced or absent β globin chain synthesis. The resulting relative excess of unbound α globin chains precipitate in erythroid precursors in the bone marrow, leading to their premature death and, hence, to ineffective erythropoiesis. β-thalassemia phenotypes are variable, ranging from the severe transfusion dependent thalassemia major to the mild form of thalassemia intermedia.2 When transfusion therapy is considered, careful attention to the potential risks of iron overload should be made.3
1 Manolova V, Flace A, Altermatt P et al. Ferroportin Inhibitors Improve Ineffective Erythropoeisis and Prevent Iron Loading in a Beta-Thalassemia Disease Model. BioIron Congress 2017; Abstract
2 Danjou F, Anni F, Galanello R. Beta-thalassemia: from genotype to phenotype. Haematologica 2011;96:1573–753
3 Taher A, Vichinsky E, Musallam K et al. Guidelines for the Management of Non Transfusion Dependent Thalassemia (NTDT). 2ND EDITION Thalassemia International Federation. Publication No. 22; ISBN 978-9963-717-11-8
SOURCE: Vifor Pharma