Date: 2014-06-13
Type of information: Presentation of results at a congress
phase: 2a
Announcement: presentation of results at the 19th Congress of the European Hematology Association (EHA) in Milan, Italy
Company: Noxxon Pharma (Germany)
Product: lexaptepid pegol (NOX-H94)
Action
mechanism: Lexaptepid pegol (NOX-H94) is a Spiegelmer® (chemically synthesized, non-immunogenic alternative to antibodies) designed to treat anemia of chronic disease by targeting the peptide hormone hepcidin, the keyregulator of iron metabolism. Hepcidin is up-regulated by acute and chronic inflammatory reactions resulting in “iron restriction”, which means that iron is blocked inside cellular stores and not available for hemoglobin synthesis1. This is in contrast to “iron deficiency”, in which iron stores are depleted.
Excessive concentrations of the peptide hormone hepcidin, which is also called the master regulator of iron homeostasis, occur in some chronic diseases such as cancer, renal disease, or inflammatory diseases. These high hepcidin levels lead to iron restriction, also known as functional iron deficiency: a condition in which iron is blocked inside its cellular stores and is thus unavailable for hemoglobin synthesis. This condition, over time, results in anemia of chronic disease. NOX-H94 inhibits this pathological mechanism by binding and inactivating hepcidin.
Disease: anemia associated with chronic disease as infections, cancers, autoimmune diseases and chronic kidney diseases
Therapeutic area: Infectious diseases - Hematological diseases - Cancer - Oncology - Autoimmune diseases - Renal diseases - Kidney diseases
Country: Europe
Trial
details: The NOX-H94 Phase IIa study is being conducted to investigate the hypothesis that inhibition of hepcidin can raise hemoglobin levels in patients with anemia of chronic disease. The four-week repeated-dose multi-center study will be conducted in Europe in anemic patients with cancer. An open-label pilot phase will be followed by a 3-arm randomized, double-blind, placebo-controlled main phase comparing two different dose-regimens of NOX-H94 with placebo. Twelve cancer patients with anemia (hemoglobin < 10 g/dL) were treated for four weeks with twice weekly intravenous infusions of lexaptepid pegol. This treatment period was followed by a one month observation period. No treatment with ESAs (erythropoiesis stimulating agents) such as EPO (erythropoietin) or iron products was allowed during the study period.
Latest
news: * On June 13, 2014, NOXXON Pharma presented the outcome of a Phase IIa pilot study on the anti-hepcidin Spiegelmer® lexaptepid pegol (NOX-H94) for treating anemia of chronic diseases at the 19th Congress of the European Hematology Association (EHA) in Milan, Italy, from 12-15 June 2014. The results of this pilot trial of lexaptepid pegol monotherapy in anemic cancer patients showed pharmacodynamic responses (ferritin decreases) in 10 of 12 patients and hemoglobin increases of 1g/dL or more in 5 of 12 patients supporting the concept of hepcidin inhibition as valuable treatment of anemia of cancer. Increased hepcidin levels, commonly found in anemic patients with cancer or on dialysis, lead to iron restriction, also known as functional iron deficiency: a condition in which iron is blocked in its cellular stores and is thus unavailable for hemoglobin synthesis. The titles and contributors for the four above mentioned poster presentations at EHA are as follows: Abstract P1172: THE ANTI-HEPCIDIN SPIEGELMER® LEXAPTEPID PEGOL (NOX-H94) AS TREATMENT OF ANEMIA OF CHRONIC DISEASE IN PATIENTS WITH MULTIPLE MYELOMA, LOW GRADE LYMPHOMA, AND CLL: A PHASE II PILOT STUDY. Pencho Georgiev, Mihaela Lazaroiu, Luminita Ocroteala, Janet Grudeva-Popova, Emanuil Gheorghita, Mariana Vasilica, Sanda Popescu, Andrei Cucuianu, Luciana Summo, Stéphanie Vauléon, Stefan Zöllner, Frank Schwoebel, Kai Riecke, Heinz Ludwig * On April 8, 2014, Noxxon Pharma has announced that data from a Phase IIa pilot study in anemic cancer patients treated with lexaptepid pegol (NOX- H94) will be presented at the annual meeting of the American Association for Cancer Research (AACR) in San Diego, CA. The objective of this single-arm, open label, multi-center study was to evaluate the efficacy, pharmacokinetics, safety and tolerability of treatment with lexaptepid pegol. The results showed significant increases in hemoglobin levels (>1 g/dL) in 5 of 12 (42%) patients in response to lexaptepid pegol monotherapy. Increased hemoglobin was maintained throughout the follow-up period. For reference, the combination of EPO and intravenous iron in a similar population resulted in a response in 65% of patientsi. Lexaptepid pegol responders showed increases of both red cell and reticulocyte hemoglobin and a decrease in soluble transferrin receptor levels. This latter marker is an indicator of increased iron demand, and was identified as one of two promising diagnostic predictors along with reticulocyte hemoglobin content.Following this positive pilot study, NOXXON plans to initiate soon a new study with lexaptepid pegol in EPO-hyporesponsive dialysis patients. * On December 4, 2012, Noxxon Pharma has announced the treatment of the first patients in a Phase IIa clinical trial of its anti-hepcidin Spiegelmer® NOX-H94 to treat anemia associated with chronic disease. This Phase IIa study was initiated following the successful completion of the clinical Phase I program, data from which will be presented at the upcoming ASH (American Society of Hematology) meeting in Atlanta, Georgia, 8-11 Dec 2012. The Phase I program consisted of a comprehensive single and multiple ascending dose study in healthy volunteers and a subsequent human pharmacodynamic study to assess the ability of NOX-H94 to prevent endotoxin-induced hypoferremia in healthy subjects. This endotoxemia study delivered the first clinical evidence that NOX-H94 is capable of neutralizing high levels of hepcidin in humans and maintaining higher serum iron concentrations relative to subjects receiving placebo. NOX-H94 is the third Spiegelmer® to enter Phase II studies and this study is the fourth Phase IIa trial that Noxxon has started this year. The other Phase IIa studies initiated in 2012 include the NOX-E36 Phase IIa for the treatment of diabetic nephropathy, the NOX-A12 Phase IIa for the treatment of Chronic Lymphocytic Leukemia, and the NOX-A12 Phase IIa for the treatment of Multiple Myeloma.
