NOXXON Pharma today 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.
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.
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.
Hepcidin inhibitors such as NOX-H94 offer the potential to provide a targeted treatment alternative for anemia of chronic disease and to avoid some of the disadvantages of the existing unspecific therapies which are often given at supra-physiological doses: erythropoiesis-stimulating agents (ESAs), i.v. iron, and blood transfusions:
the potential risks of ESAs in the treatment of patients with cancer and chronic kidney disease are documented in the black box warning required by the US FDA and include increased risk of tumor progression or recurrence;
use of i.v. iron has increased in response to concerns with ESAs; but this therapy is limited by the potential occurrence of iron overload, in addition administration of i.v. iron leads to a counter-productive increase in hepcidin;
blood transfusions also add iron to the body and in addition bring the risks of transmissible diseases and immunosuppression.
NOX-H94 is the first hepcidin inhibitor to reach Phase II.
Based on information from the GLOBOCAN database and scientific publications on rates and types of anemia in cancer and chronic kidney disease (CKD) patients, NOXXON estimates that there are approximately 230,000 cancer patients and 3.6 million CKD patients requiring treatment for anemia of chronic disease every year that could potentially benefit from a hepcidin inhibitor in the combined markets of the EU-5 (France, Germany, Italy, Spain and the United Kingdom), Japan and the United States.