Skip to main content
Article thumbnail
Location of Repository

Chronic Pharmacological and Safety Evaluation of Hematide™, a PEGylated Peptidic Erythropoiesis-Stimulating Agent, in Rodents

By Kathryn W Woodburn, Susan D Wilson, Kei-Lai Fong, Peter J Schatz, Charles B Spainhour and Daniel Norton


Hematide™ is a synthetic peptide-based, PEGylated erythropoiesis-stimulating agent, which is being developed for the chronic treatment of anaemia associated with chronic renal failure. To support the safety of long-term dosing of chronic renal failure patients, a comprehensive toxicology programme was implemented including rat subchronic and chronic studies. Rats were administered 0, 0.1, 1 and 10 mg/kg of Hematide every 3 weeks for 3 months via subcutaneous injection or for 6 months via intravenous injection. The dosing period was followed by a 6-week follow-up period. The primary pharmacology of Hematide resulted in erythroid polycythemia as measured by elevated haemoglobin levels that were time-and dose-dependent. The pharmacology profiles were similar regardless of administration route. For example, for male rats at Day 90, subcutaneous dosing resulted in haemoglobin increases of 2.7, 4.5 and 6.9 g/dl for 0.1, 1 and 10 mg Hematide/kg respectively, compared to 2.8, 5.7 and 7.4 g/dl increases for intravenous dosing. Histopathological changes were related to the prolonged severe polycythemia induced in normocythemic animals administered an erythropoiesis-stimulating agent. The findings included extramedullary haematopoiesis in the spleen and liver, bone marrow hypercellularity and organ congestion. Microscopic findings were reversible, demonstrating a return towards control findings within 6 weeks following cessation of dosing. Systemic exposures, based on both area under the curve (AUC) and maximum concentration (Cmax), were substantially greater for intravenous than subcutaneous administration. No Hematide-specific antibodies were detected. In conclusion, Hematide is a potent erythropoiesis-stimulating agent, and the studies provide support for the safety of clinical development, including chronic dosing, for the treatment of anaemia associated with chronic renal failure

Topics: Original Articles
Publisher: Blackwell Publishing Inc
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2003). Anemia: not just an innocent bystander? Arch Intern Med
  2. Casadevall N et al . Hematide is immunologically distinct from erythropoietin and corrects anemia induced by antierythropoietin antibodies in a rat pure red cell aplasia model. Exp Hematol,
  3. Duliege A-M et al . Treatment of erythropoietin antibody-mediated pure red cell aplasia with a novel synthetic peptide-based erythropoietin receptor agonist [abstract].
  4. New agents that stimulate erythropoiesis.
  5. (2003). Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev
  6. (1990). The anemia of chronic renal failure: pathophysiology and effects of recombinant erythropoietin. Contrib Nephrol
  7. Velkovska S et al . Preclinical evaluation of Hematide, a novel erythropoiesis stimulating agent, for the treatment of anemia. Exp Hematol

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.