Eltrombopag, a novel, oral platelet growth factor, increases platelet counts in thrombocytopenic patients and healthy subjects

Abstract

8602 Background: Eltrombopag (SB-497115) is a novel, first in class, orally bioavailable, thrombopoietin receptor agonist that induces differentiation and proliferation of megakaryocyte progenitors and has been shown to increase platelet counts in preclinical and clinical studies. Methods: In two randomized, placebo-controlled trials, eltrombopag was administered as oral tablets, once daily for 10 days to 73 healthy male subjects at doses of 5–75mg in an ascending dose cohort study, and to 103 (64 female/39 male) adult chronic immune thrombocytopenic purpura (ITP) patients, with a platelet count of <30×109/L, once daily for 6 weeks at doses of 30–75mg in a parallel dose cohort study. The primary efficacy endpoint in the Phase II ITP trial was the proportion of subjects with a platelet count >50×109/L after 6 weeks of dosing. Results: In healthy subjects, eltrombopag induced a dose dependent increase in the platelet counts. Mean maximal platelet count increases were 24.1 % at 30mg, 42.9 % at 50mg, and 50.4 % at 75mg. In 95 eligible ITP patients, platelet counts increased from <30 to >50×109/L in 16% (4/25) of subjects on placebo, and in the eltrombopag groups in 28% (7/25, p=ns) on 30mg, 67% (16/24, p<0.001) on 50mg and 86% (18/21, p<0.001) on 75mg eltrombopag. The median platelet counts in each treatment arm after 6 weeks of dosing were 16×109/L on placebo, 29×109/L on 30mg, 132×109L on 50mg, and 202×109/L on 75mg. The dose dependent effect was not significantly affected by the splenectomy status, background immunosuppressant use, or baseline platelet count (greater than or less than 15×109/L). Conclusions: The platelet count data from these clinical studies suggests that eltrombopag could be an effective therapy for the treatment of thrombocytopenia. Eltrombopag is being tested in further studies involving patients with ITP and chronic liver disease, and cancer patients receiving thrombocytopenic chemotherapy. [Table: see text]