Oral Drug Raises Plate Counts in Patients with Liver Disease

and Revolade in Europe) is an investigational oral, non-peptide platelet growth factor that induces the proliferation and differentiation of cells to produce platelets. While other drugs that restore normal platelet functions are infusions or injections, eltrombopag is a once-a-day pill. The current studies were sponsored by GlaxoSmithKline (Brentford, Middlesex, UKcom), the developer of eltrombopag.

Investigators at Weill Cornell Medical College (New York, NY, USA) worked with patients suffering from low platelet counts due to either infection with the hepatitis C virus (HCV) or from chronic idiopathic thrombocytopenic purpura (ITP). In both cases, initial platelet counts were less than 30,000 per milliliter, which is far below the normal level of about 150,00 to 450,000 per milliliter.

In one study, 74 patients with HCV-related cirrhosis and platelet counts of 20,000 to less than 70,000 per cubic millimeter were randomly assigned to receive eltrombopag (30, 50, or 75 mg daily) or a placebo daily for four weeks. The primary end point was a platelet count of 100,000 per cubic millimeter or more at week four. In the other study 118 adults with chronic ITP and platelet counts of less than 30,000 per cubic millimeter who had had relapses or whose platelet count was refractory to at least one standard treatment for ITP were randomly assigned to receive eltrombopag (30, 50, or 75 mg daily) or a placebo. The primary end point was a platelet count of 50,000 or more per cubic millimeter on day 43.

Results published in the November 29, 2007, edition of the New England Journal of Medicine (NEJM) revealed that in the HCV study, week four platelet counts were increased to 100,000 per cubic millimeter or more in a dose-dependent manner in 0 of the 17 patients receiving placebo, in nine of 12 (75%) receiving 30 mg of eltrombopag, in 15 of 19 (79%) receiving 50 mg of eltrombopag, and in 20 of 21 (95%) receiving 75 mg of eltrombopag.

Results in the ITP study showed that in the eltrombopag groups receiving 30, 50, and 75 mg per day, the primary end point was achieved in 28%, 70%, and 81% of patients, respectively. In the placebo group, the end point was achieved in 11% of patients. The median platelet counts on day 43 for the groups receiving 30, 50, and 75 mg of eltrombopag were 26,000, 128,000, and 183,000 per cubic millimeter, respectively; for the placebo group the count was 16,000 per cubic millimeter. By day 15, more than 80% of patients receiving 50 or 75 mg of eltrombopag daily had an increased platelet count. Bleeding also decreased during treatment in these two groups. In both studies, some patients experienced side effects including headaches, dry mouth, abdominal pain, and nausea. None were serious enough to discontinue the therapy.

Relating to the HCV study, contributing author Dr Samuel Sigal, assistant professor of medicine at Weill Cornell Medical College, said, "In this study, eltrombopag increased platelet counts in a dose-dependent manner, allowing more patients to complete the first 12 weeks of antiviral therapy--an important treatment goal.”


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