Affymax, Inc and Takeda Pharmaceutical Global Research & Development Center, Inc, announced data from a phase-2 clinical trial of Hematide showing that Hematide increased haemoglobin and reduced or eliminated the need for blood transfusion in most patients with erythropoietin-induced pure red cell aplasia (PRCA). The data were published in the November 5, 2009 issue of the New England Journal of Medicine.

In the open-label, non-randomized trial, patients with chronic kidney disease (CKD), who had anti-erythropoietin antibody-mediated PRCA and who were anaemic, generally experienced increases in haemoglobin above 11 g/dL following once monthly injections of Hematide.

PRCA is a rare, serious and debilitating autoimmune disorder, which can occur when the body produces neutralizing antibodies against the currently marketed recombinant human erythropoietins, such as epoetin alfa or beta and darbepoetin alfa, thus suppressing the production of red blood cells by the bone marrow. While PRCA is a rare disorder, it remains a concern among physicians and patients as it can significantly limit treatment options for anaemia in patients with CKD and requires these patients to receive regular blood transfusions. Hematide is under development for the treatment of anaemia associated with chronic renal failure, including patients on chronic dialysis and not on dialysis. Hematide is a novel investigational synthetic, PEGylated peptide-based erythropoietin (EPO) receptor agonist with no sequence homology with human EPO, and hence is not expected to induce PRCA.

"These data suggest that Hematide may be a promising anaemia treatment alternative for patients in this population, with a different immunogenicity profile than other erythropoiesis-stimulating agents," said Iain C Macdougall, consultant nephrologist in the Department of Renal Medicine at King's College Hospital in London, Hematide clinical investigator and lead author of the New England Journal of Medicine article. "Hematide stimulated red blood cell production in most patients with antibody-mediated PRCA and thereby diminished these patients' dependence on blood transfusions. Additionally, following the start of treatment with Hematide, most patients experienced a decline in their levels of neutralizing anti-EPO antibodies associated with the underlying PRCA condition."

The purpose of this study was to test whether Hematide given subcutaneously can stimulate red blood cell production in patients with anti-EPO antibodies, who otherwise had a compromised ability to generate red blood cells. Fourteen patients were treated with Hematide for a median of 28 months (range 3-36). Thirteen of the 14 patients (93 per cent) achieved the primary endpoint of an increase in hemoglobin to a level greater than 11 g/dL without the need for regular blood transfusions. While the number of patients tested is small, the beneficial effect was consistent and sustained for up to 156 weeks. Further, in six of 14 patients, titers of anti-erythropoietin antibodies fell below the detection limit following treatment with Hematide.

Overall, adverse events were generally mild or moderate in severity. Adverse events that were possibly related to Hematide were hypertension, bone pain and injection site hematoma. Two serious adverse events were considered possibly related to Hematide (severe anaemia and lack of response) and both occurred in a patient who developed anti-Hematide antibodies. This patient initially responded to Hematide, but later had a diminished clinical response despite increasing doses of the drug.

"We are encouraged by these findings, which suggest fundamental differences with Hematide compared to commercially available ESAs," said Anne-Marie Duliege, chief medical officer of Affymax. "If approved, we believe that Hematide could represent a significant new treatment option for providers caring for patients with chronic renal failure."

Hematide is a synthetic, peptidic erythropoiesis stimulating agent (ESA) linked to polyethylene glycol (PEG) that is being developed for the treatment of anemia associated with chronic renal failure.

Dialysis and non-dialysis patients with CKD frequently develop anemia because of a reduction in native EPO production by dysfunctional kidneys.

Affymax is a biopharmaceutical company committed to developing novel drugs to improve the treatment of serious and often life-threatening conditions.