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Previous Volume 361:1848-1855 November 5, 2009 Number 19 Next

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ABSTRACT

Background We investigated whether a novel, synthetic, peptide-based erythropoietin-receptor agonist (Hematide, Affymax) can stimulate erythropoiesis in patients with anemia that is caused by antierythropoietin antibodies.

Methods In this open-label, single-group trial, we enrolled patients with chronic kidney disease who had pure red-cell aplasia or hypoplasia due to antierythropoietin antibodies and treated them with a synthetic peptide-based erythropoietin-receptor agonist. The agonist was administered by subcutaneous injection at an initial dose of 0.05 mg per kilogram of body weight every 4 weeks. The primary end point was a hemoglobin concentration above 11 g per deciliter without the need for transfusions.

Results We treated 14 patients with the peptide agonist for a median of 28 months. The median hemoglobin concentration increased from 9.0 g per deciliter (with transfusion support in the case of 12 patients) before treatment to 11.4 g per deciliter at the time of the last administration of the agonist; transfusion requirements diminished within 12 weeks after the first dose, after which 13 of the 14 patients no longer required regular transfusions. Peak reticulocyte counts increased from a median of 10x10⁹ per liter before treatment to peak counts of greater than 100x10⁹ per liter. The level of antierythropoietin antibodies declined over the course of the study and became undetectable in six patients. One patient who initially responded to treatment had a diminished hematologic response a few months later despite increased doses of the agonist and required transfusions again; this patient was found to have antibodies against the agonist. One patient died 4 months after the last dose of the agonist, and a grade 3 or 4 adverse event occurred in seven other patients during the study period.

Conclusions This novel agonist of the erythropoietin receptor can correct anemia in patients with pure red-cell aplasia caused by antierythropoietin antibodies. (ClinicalTrials.gov number, NCT00314795 [ClinicalTrials.gov] .)

Source Information

From the Department of Renal Medicine, King's College Hospital, London (I.C.M.); the Departments of Nephrology (J.R.) and Physiology (M.F.), Georges Pompidou European Hospital, Assistance Publique–Hôpitaux de Paris; Paris-Descartes University (J.R., M.F.); and the Department of Hematology, Hôpital Saint Antoine, Assistance Publique–Hôpitaux de Paris and Pierre et Marie Curie University (N.C.) — all in Paris; INSERM Unité 790, Villejuif, France (N.C.); BioPharma Consulting Services, Bellevue, WA (R.B.S.); Affymax, Palo Alto, CA (A.-M.D.); and the Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany (K.-U.E.).

Address reprint requests to Dr. Macdougall at the Renal Unit, King's College Hospital, London SE5 9RS, United Kingdom, or at iain.macdougall{at}kch.nhs.uk.

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• Bunn, H. F. (2009). End Run around Epo. NEJM 361: 1901-1903 [Full Text]  
• (2009). A Novel Erythropoietin Receptor Agonist for Red Cell Aplasia. JWatch Oncology and Hematology 2009: 1-1 [Full Text]