Date: 2015-05-29
Type of information: Presentation of results at a congress
phase: 2a
Announcement: presentation of results at the 52nd annual meeting of the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) conference in London
Company: Noxxon Pharma (Germany)
Product: lexaptepid pegol (NOX-H94)
Action
mechanism: spiegelmer. 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. High hepcidin levels, commonly found in dialysis patients, lead to iron restriction, also known as functional iron deficiency. This condition, in which iron is blocked inside its cellular stores and therefore unavailable for hemoglobin synthesis, ultimately results in anemia. NOX-H94 inhibits this pathological mechanism by binding and inactivating hepcidin.
Disease: erythropoietin (EPO)-hyporesponsive anemia in dialysis patients
Therapeutic area: Kidney diseases - Renal diseases
Country: UK
Trial
details: The Spiegelmer lexaptepid pegol (NOX-H94) offers a hepcidin-specific approach to the treatment of anemia of chronic disease. The safety and the activity of lexaptepid pegol are supported by data from healthy subjects and patients with multiple myeloma or lymphoma. The present study in dialysis patients with functional iron deficiency and ESA-hyporesponsiveness is conducted to demonstrate the safety of lexaptepid pegol in this population, to investigate its pharmacokinetic (PK) and pharmacodynamic (PD) profiles and its efficacy in increasing haemoglobin (Hb) in dialysis patients. (NCT02079896)
Latest
news: * On May 29, 2015, Noxxon Pharma announced that results from Part 1 of its two-part Phase 2a trial of the anti-hepcidin Spiegelmer® NOX-H94 in erythropoiesis-stimulating agent (ESA)-hyporesponsive dialysis patients were reported at the 52nd annual meeting of the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) conference in London. This trial is investigating the tolerability, pharmacokinetics, iron mobilization effects and efficacy of NOX-H94 in the treatment of ESA-hyporesponsive anemia. Approximately 10% of the anemic dialysis population in the US is hyporesponsive to treatment with ESAs, and thus these patients end up receiving higher doses of these agents to treat their anemia. As a result, the 10% of patients that are ESA-hyporesponders consume approximately 40% of all erythropoietin administered in the dialysis population. One factor believed to contribute to ESA-hyporesponsiveness is hepcidin, a peptide hormone increased by inflammation that is a key regulator of iron in the human body. Hepcidin shuts off iron supply to erythropoietic tissue in the bone marrow and blocks iron absorption from dietary sources, thereby preventing incorporation of iron into the oxygen carrying protein, hemoglobin. NOX-H94 offers the potential for a more effective treatment of this population by binding and neutralizing hepcidin. Nine patients were enrolled in Part 1 of the trial in which the single-blind cross-over design called for each patient to receive sequentially one administration each of placebo and NOX-H94. Treatment with NOX-H94 was generally well tolerated and all adverse events observed were considered unrelated to treatment. The results showed that no adjustment of the dosing will be required in dialysis patients for the second part of the clinical trial and that the expected effect of increased serum iron levels was seen following NOX-H94 administration. This is the fourth clinical trial with lexaptepid pegol. Lexaptepid pegol (NOX-H94), an anti-hepcidin Spiegelmer®, has completed a Phase IIa pilot study in cancer patients with anemia and is now being studied in EPO-hyporesponsive dialysis patients.
As a result of the data seen in Part 1 of this trial, Noxxon has elected to initiate Part 2. Dosing of the first of 24 patients in Part 2 has already begun, half of whom will receive NOX-H94, and the other half placebo, twice per week for four weeks. Patients that
respond with a pre-defined increase of hemoglobin will be considered responders. The company plans to announce top-line data in the fourth quarter of 2015.
* On July 31, 2014, Noxxon Pharma announced the treatment of a first patient with its anti-hepcidin Spiegelmer® lexaptepid pegol (NOX-H94) in a phase IIa proof-of-concept clinical trial to treat erythropoietin (EPO)-hyporesponsive anemia in dialysis patients. The multi-center, placebo-controlled study will examine the pharmacokinetics, pharmacodynamics, efficacy and safety of single and multiple doses of lexaptepid pegol in EPO-hyporesponsive dialysis patients with anemia. Approximately 10% of the dialysis population has erythropoiesis-stimulating agent (ESA)-resistant anemia, an unmet medical need that NOXXON now addresses with this study. Anemic dialysis patients that do not respond adequately to an ESA could benefit from the inhibition of hepcidin by lexaptepid pegol. A recent study by Noxxon, presented at the AACR meeting and the EHA congress in 2014, has already shown significant increases in hemoglobin levels (>1 g/dL) in response to lexaptepid pegol monotherapy in a subset of anemic cancer patients.
