The primary hematopoietic activity of Neumega is stimulation of megakaryocytopoiesis and thrombopoiesis. Neumega has shown potent thrombopoietic activity in animal models of compromised hematopoiesis, including moderately to severely myelosuppressed mice and nonhuman primates. In these models, Neumega improved platelet nadirs and accelerated platelet recoveries compared to controls.

Preclinical trials have shown that mature megakaryocytes which develop during in vivo treatment with Neumega are ultrastructurally normal. Platelets produced in response to Neumega were morphologically and functionally normal and possessed a normal life span.

IL-11 has also been shown to have non-hematopoietic activities in animals including the regulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), the inhibition of adipogenesis, the induction of acute phase protein synthesis, inhibition of pro-inflammatory cytokine production by macrophages, and the stimulation of osteoclastogenesis and neurogenesis. Non-hematopoietic pathologic changes observed in animals include fibrosis of tendons and joint capsules, periosteal thickening, papilledema, and embryotoxicity (see PRECAUTIONS, Pediatric Use and PRECAUTIONS, Pregnancy Category C).

IL-11 is produced by bone marrow stromal cells and is part of the cytokine family that shares the gp130 signal transducer. Primary osteoblasts and mature osteoclasts express mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Both bone-forming and bone-resorbing cells are potential targets of IL-11.(1)

The pharmacokinetics of Neumega have been evaluated in studies of healthy, adult subjects and cancer patients receiving chemotherapy. In a study in which a single 50 mg/kg subcutaneous dose was administered to eighteen healthy men, the peak serum concentration (C_max) of 17.4 ± 5.4 ng/mL (mean ± S.D.) was reached at 3.2 ± 2.4 hrs (T_max) following dosing. The terminal half-life was 6.9 ± 1.7 hrs. In a second study in which single 75 mg/kg subcutaneous and intravenous doses were administered to twenty-four healthy subjects, the pharmacokinetic profiles were similar between men and women. The absolute bioavailability of Neumega was >80%. In a study in which multiple, subcutaneous doses of both 25 and 50 mg/kg were administered to cancer patients receiving chemotherapy, Neumega did not accumulate and clearance of Neumega was not impaired following multiple doses.

In a dose escalation Phase 1 study, Neumega was also administered to 43 pediatric patients (ages 8 months to 18 years) and 1 adult patient receiving ICE (ifosfamide, carboplatin, etoposide) chemotherapy. Administered doses ranged from 25 to 125 mg/kg. Analysis of data from 40 pediatric patients showed that C_max, T_max, and terminal half-life were comparable to that in adults. The mean area under the concentration-time curve (AUC) for pediatric patients (8 months to 18 years), receiving 50 mg/kg was approximately half that achieved in healthy adults receiving 50 mg/kg. Available data suggest that clearance of oprelvekin decreases with increasing age.

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