Abstract
Introduction: Hematide™ a novel, synthetic, PEGylated peptidic compound, binds to and activates the erythropoietin receptor. It is in development for treatment of anemia associated with chronic renal failure and cancer.
Objective: To assess the subcutaneous (SC) Hematide™ dose required to increase hemoglobin (Hb) by ≥ 1 g/dL in ≥ 50% of anemic cancer patients (pts) on chemotherapy. Safety, pharmacodynamics and pharmacokinetics were also assessed.
Method: In a phase 2, open label, multi-center, dose finding study, up to four doses of Hematide™ were given SC every 3 wks (Q3W) to 4 cohorts of fifteen pts at 0.05, 0.10, 0.15 or 0.2 mg/kg each. Entry criteria included confirmed solid tumor malignancy or lymphoma, >9 weeks of chemotherapy, baseline (BL) H ≥ 8 and <11 g/dL, and adequate iron, folate and B12 stores.
Results: Sixty patients were enrolled (45% male). Preliminary data show that across cohorts 0.05, 0.10, 0.15 and 0.20 mg/kg, mean (BL) Hb values were 10.1(±1.07), 10.0(±0.89), 9.8(±0.67), 10.1(±0.69); the % of pts completing the study were approximately 79%, 50%, 60%, and 92%. An increase in mean Hb from BL of ≥ 1g/dL in the pharmacodynamic dataset (forty two pts) at Week 7 occurred in approximately 20%, 70%, 55% and 55% of patients. Three pts withdrew due to AEs and six due to SAEs (none attributed to study drug). Three deaths occurred (two disease progression, one renal insufficiency) none attributed to study drug. One SAE, thrombophlebitis, was considered to be possibly/probably related to study drug. Final safety and efficacy data will be provided at the meeting.
Conclusion: In this study, HematideTM dosed SC Q3W resulted in an increase from BL of ≥ 1 g/dL of Hgb in ≥ 50% of patients in the 0.10, 0.15 and 0.20 mg/kg cohorts in the pharmacodynamic analysis. HematideTM appeared to be well tolerated at all doses studied.
Pharmacodynamic analysis of stress erythropoiesis: change in erythropoietin receptor pool size following double phlebotomies in sheep
