PHARMACEUTICAL NEWS

Oral Thrombopoietin Receptor Agonist Eltrombopag: New Drug for Chronic Idiopathic Thrombocytopenic Purpura

On December 4, 2008, the US Food and Drug Administration (FDA) approved GlaxoSmithKline’s eltrombopag (Promacta^®) for adult patients with chronic idiopathic thrombocytopenic purpura (ITP) who have demonstrated an inadequate response to corticosteroids, immunoglobulins, or splenectomy.

Approval of this thrombopoietin receptor agonist was supported by a unanimous decision from the FDA's Oncology Drugs Advisory Committee based primarily on data from 2 pivotal studies demonstrating the favorable nature of the risk-benefit profile of eltrombopag in short-term therapy. In these studies, patients who completed at least one previous regimen of ITP therapy and had a platelet count of less than 30 x 109/L were randomized to either daily placebo or eltrombopag administered for a maximum treatment period of 6 weeks followed by 6 weeks of no treatment. Treatment was discontinued if platelet counts exceeded 200 x 10⁹/L.

In both studies, 50 mg/day of eltrombopag was significantly more effective than placebo in achieving a platelet count response, defined as an increase from less than 30 x 10⁹/L at baseline to at least 50 x 10⁹/L at any time during the treatment period.

In these studies, hemorrhage was the most common serious adverse reaction, with most cases occurring after discontinuation of eltrombopag. Other serious events included liver test abnormalities and thrombotic or thromboembolic complications.

Eltrombopag therapy should be initiated at a dose of 50 mg once daily, except in patients of East Asian ancestry or in those who have moderate-to-severe hepatic impairment. For these patients, the recommended starting dose is 25 mg once daily. Clinical hematologic and liver tests should be performed regularly during the course of treatment.

Second Generation Tyrosine Kinase Inhibitor Nilotinib Now Approved in Japan

On January 21, 2009, Japanese authorities approved Novartis’ nilotinib (Tasigna^®) for the treatment of Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in adult patients who are resistant to imatinib (Gleevec^®/Glivec^®).

The approval in Japan was supported by 2 studies that investigated the efficacy of nilotinib in the chronic and accelerated phases of the disease. In the international phase II study, 42% of patients in the chronic phase of CML achieved a major cytogenetic response, while 66% of patients in the CML accelerated phase achieved a hematologic response. In the Japanese study, the response rates were 94% in the chronic phase and 71% in the accelerated phase.

Nilotinib was approved by the FDA in October 2007 and by the European Medicines Agency (EMEA) in November 2008 for the treatment of patients with imatinib-resistant/intolerant CML.

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