Promacta (eltrombopag) shown to increase platelet counts and reduce bleeding in chronic immune thrombocytopenic

GlaxoSmithKline has announced positive safety and efficacy results from RAISE (RAndomized placebo- controlled ITP Study with Eltrombopag), a Phase III study of Promacta (eltrombopag) in adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who had received one or more prior ITP therapies.

Patients receiving Promacta were eight times more likely than those on placebo to maintain platelet counts between 50,000 to 400,000/microliters during a six- month treatment period, thereby reducing patients' bleeding symptoms and their need for concomitant and rescue ITP treatments. These data were presented at the 50th Annual Meeting of the American Society of Hematology (ASH), December 6-9, 2008, in San Francisco, CA.

"Promacta is the first approved agent to show that generating platelets can be achieved and maintained with an oral therapy," said Paolo Paoletti, M.D., Senior Vice President of Oncology R&D, GSK. "With the continued emergence of GSK in oncology, we want patients and physicians to continuously benefit from our dedication to developing truly innovative treatments that can help improve patients' lives. Promacta is a great example of this commitment."

Promacta received accelerated approval from the FDA on November 20 as a thrombopoietin receptor treatment for patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Promacta should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Promacta should not be used in an attempt to normalize platelet counts.

Chronic ITP is a disorder marked by increased platelet destruction and/or inadequate platelet production in the blood, which causes an increased risk of bleeding.(1) Approximately 60,000 individuals in the U.S. have the disorder.(2)

"Patients with chronic ITP often have a difficult time managing their disease. They may experience excessive bruising, bleeding and sometimes more serious hemorrhages that can rarely be fatal. Until recently, ITP patients have had few options well demonstrated to be effective in the long term," said James Bussel, M.D., director of the Platelet Disorders Center, Children's Cancer and Blood Foundation Division of New York Presbyterian/Weill Cornell Medical Center. "As the RAISE study demonstrates, Promacta is an important new oral treatment option for ITP patients that is effective in maintaining a hemostatic platelet response."

RAISE, a global, six-month, double-blind, placebo-controlled, Phase III study was designed to evaluate the safety and efficacy of Promacta in previously treated adults with chronic ITP and with platelet counts less than 30,000/microliters. The study enrolled 197 patients (Promacta: n=135; placebo: n=62) and, of these, approximately 50 percent had platelet counts less than or equal to 15,000/microliters; about 50 percent were receiving simultaneous ITP therapies at randomization; around 35 percent were splenectomized, and more than 50 percent had received at least three prior ITP medications. Patients began once daily treatment with Promacta at 50 mg (or matching placebo) with doses individualized based upon each patient's platelet response, ranging from once-daily doses of 25 mg to 75 mg, or less frequently. The baseline median platelet count in both the placebo and the Promacta groups was 16,000/microliters.

Throughout the study, the median platelet count in the placebo group never exceeded 30,000/microliters. By contrast, after just one week, patients in the Promacta arm experienced a rise in their median platelet count to 36,000/microliters, with median platelet levels subsequently ranging from 52,000 to 91,000/microliters for the remainder of the study, meeting the study's primary endpoint of odds of responding (platelets 50,000 to 400,000/microliters) during the six month treatment period. Patients receiving Promacta were eight times more likely to achieve an overall response of increased platelet counts of 50,000 to 400,000/microliters than those taking placebo (Odds ratio = 8.2; 99 percent CI [3.59, 18.73]; p < 0.001). In comparison to the placebo group, significantly fewer patients treated with Promacta had any bleeding or clinically significant (WHO Grades 2-4; p < 0.001) bleeding throughout the trial and more patients in the Promacta group (59 percent) stopped or reduced their simultaneous ITP medications than in the placebo group (32 percent; p = 0.016). In addition, during the treatment phase of the study, fewer patients in the Promacta arm (19 percent) required rescue therapy compared with those in the placebo arm (40 percent, p = 0.001).

The overall incidence of adverse events was similar between the Promacta (87 percent) and placebo groups (92 percent), which were mostly mild to moderate in severity. Headache was the most common adverse event in both groups (greater than or equal to 30 percent). Two corticosteroid-associated adverse events (dyspepsia and peripheral edema) were significantly less likely to occur in the Promacta group compared to the placebo group; however, a higher incidence of hepatobiliary laboratory abnormalities were reported in patients taking Promacta (13 percent) compared with those in the placebo group (7 percent). These abnormalities were not predictive of serious, drug-induced liver injury. One death was reported in the placebo group. There were no clinical or laboratory symptoms suggestive of bone marrow fibrosis in patients taking Promacta.