Eltrombopag (Promacta): Thrombopoietin (TPO) receptor agonist approved for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP)

New molecular entity: Eltrombopag (Promacta), a TPO receptor agonist, was approved on November 20, 2008, for the treatment of thrombocytopenia in patients with chronic ITP.

Eltrombopag is a thrombopoietin (TPO) receptor agonist that initiates signaling cascades by binding to the transmembrane domain of the human TPO receptor, thereby inducing proliferation and differentiation of megakaryocytes. This agent was approved on November 20, 2008, for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Efficacy. The efficacy of eltrombopag was assessed in 2 randomized, double-blind, placebo-controlled trials (Studies 1 and 2) and in an open-label extension study. Studies 1 and 2 enrolled patients who had completed ≥1 previous ITP therapy and had a platelet count <30×109 /L. Patients were randomized to treatment with eltrombopag (Study 1, eltrombopag 50 mg/d; Study 2, eltrombopag 30, 50, or 75 mg/d) or placebo for ≤6 weeks. The primary efficacy end point was response rate, defined as an increase in platelet count to ≥50×109 /L. In Study 1, 59% of patients treated with eltrombopag 50 mg/d demonstrated a response rate versus 16% of placebo-treated patients (P<.001); in Study 2, 70% of patients treated with eltrombopag 50 mg/d demonstrated a response rate versus 11% of placebo-treated patients (P<.001). In the open-label extension study, 109 patients who had completed a previous clinical trial of eltrombopag were enrolled; 74 patients completed 3 months of treatment, 53 completed 6 months of treatment, and 3 completed 1 year of treatment with eltrombopag. The median platelet count was 74×109 /L at 3 months, 67×109 /L at 6 months, and 95×109 /L at 9 months.

Safety. This agent is available only through a restricted distribution program. Treatment with eltrombopag may cause hepatotoxicity. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels should be measured before and during treatment. TPO receptor agonists increase the risk for development or progression of reticulin fiber deposition within bone marrow. Excessive increases in platelet counts may lead to thrombotic/thromboembolic complications during treatment. Stimulation of the TPO receptor may increase the risk of hematologic malignancies. The most common adverse events associated with eltrombopag treatment include nausea, vomiting, menorrhagia, myalgia, paresthesia, and cataract.