GlaxoSmithKline (GSK) has announced additional results from an international phase II short-term, six-week study of its investigational non-peptide oral platelet growth factor, eltrombopag.
Analysis of data from this study showed that eltrombopag at 50mg or 75mg, resulted in a positive trend in decrease in bleeding incidence (all grades) in adult patients with chronic idiopathic thrombocytopenic purpura (ITP), an autoimmune condition which results in low blood platelet counts and bleeding from the small blood vessels. These data were presented at the 48th Annual American Society of Hematology (ASH) meeting in Orlando, Florida.
The primary efficacy data from this study of (a statistically significant increase in platelet counts at 50mg and 75mg doses) were previously presented at the European Society of Hematology in June 2006.
"Current treatments for ITP, such as steroids or the removal of the spleen, have limitations and side effects," says James B. Bussel, MD, director of the Platelet Disorders Centre, children's blood foundation division at the New York-Presbyterian Hospital/Weill Cornell Medical Centre and principal investigator for this trial. "Bleeding events caused by ITP, whether categorized as moderate or severe, are of great concern to patients and physicians. These study results indicate there is a potential new oral treatment that can reduce bleeding episodes."
The phase II trial was an international randomized, double-blind, placebo-controlled study that enrolled 117 adult patients with chronic ITP with baseline platelet counts of 1 Patients were randomized to placebo, 30mg, 50mg or 75mg of eltrombopag once daily for six weeks. Bleeding events were assessed weekly during treatment and biweekly after treatment via the World Health Organization (WHO) bleeding scale and by adverse event reporting.
The WHO bleeding scale measures bleeding severity from Grade 0 (no bleeding) through to Grade 4 (debilitating blood loss). The incidence of on therapy bleeding events regardless of grade and causality was 16 per cent, 3 per cent and 4 per cent in the 30mg, 50mg and 75mg eltrombopag arms respectively, versus 10 per cent in the placebo group.
At doses of 30mg, 50mg and 75mg, the median platelet count on day 43 of treatment was 26,000/mL, 128,000/mL and 183,000/mL respectively, in comparison to 16,000/mL in the placebo group. Bleeding adverse events (AEs) included the following: hemorrhoids, hemorrhagic diarrhoea and conjunctival haemorrhage in 3 patients receiving placebo; epistaxis, gingival bleeding and contusions in 5 patients receiving 30mg of eltrombopag; menorrhagia in 1 patient receiving 50mg of eltrombopag (who did not respond to eltrombopag); and contusion in patient receiving 75mg of eltrombopag.
The most common AE observed in this study was mild to moderate headache, reported in 21 per cent of subjects on placebo, and 13 per cent, 10 per cent and 21 per cent of subjects in the 30mg, 50mg and 75mg eltrombopag arms, respectively. There was no apparent relationship between dose and incidence of AEs observed in this study.3Further studies will more fully characterize the safety profile.
"We are very excit0d by these results for eltrombopag, which show great promise for chronic ITP patients who failed different lines of treatment," said Paolo Paoletti, MD, senior vice president, oncology medicine development centre, GSK. "Clinical trials for eltrombopag are ongoing, not only in ITP but also other conditions where thrombocytopenia is a clinical issue - for example liver disease and patients receiving chemotherapy. Our robust clinical trial program reflects our continued commitment in delivering novel treatments to address unmet medical needs."