Akebia Therapeutics, Inc, a small molecule discovery and development company focused on anaemia and vascular disorders, has successfully completed the first-in-man phase-1a study for AKB-6548 in healthy volunteers. AKB-6548 is an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor designed to increase the natural production of erythropoietin (EPO) in anaemic patients. In the clinical study, a single dose of AKB-6548 increased EPO levels and was found to be safe and well tolerated.

"The completion of this phase 1a study is clearly an important milestone for Akebia, and we are very pleased to have human safety data and markers of efficacy in humans," said Dr Robert Shalwitz, chief medical officer of Akebia. "After carefully selecting AKB-6548 from a series of analogs and moving it into human trials it is very gratifying to see the drug perform so well. There were no serious adverse events at any of the doses tested, and the compound produced a robust, dose responsive increase in EPO concentration. Based on the results from this phase 1a trial we look forward to moving AKB-6548 into phase 1b and 2a clinical trials in 2010.”

The phase-1a study involving 48 healthy volunteers was designed to evaluate the safety,
tolerability, pharmacokinetic and pharmacodynamic responses to single ascending doses of AKB-6548. The efficacy of AKB-6548 was determined by measuring EPO and other biomarker responses. In particular, doses of AKB-6548 producing significant increases in EPO did not change levels of vascular endothelial growth factor (VEGF). VEGF is a biomarker that potentially is upregulated by HIF stabilization. Separation of the EPO response from a VEGF response is critical for a chronic therapeutic that may be used in patients with anaemia associated with either chemotherapy or chronic kidney disease. The Phase 1a trial was conducted at Medpace, Inc. in Cincinnati, Ohio.

Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in oxygen, or hypoxia, in the cellular environment.

AKB-6548 is an orally bioavailable HIF-PH inhibitor designed to increase natural production of EPO, a glycoprotein hormone that controls red blood cell production.

Akebia Therapeutics is a discovery and development company focused on anaemia and vascular disorders.