GlaxoSmithKline plc has announced results from an international, pivotal phase III study of its investigational non-peptide oral platelet growth factor, Revolade (eltrombopag).

Data from this study showed that eltrombopag at 50-75mg once daily resulted in a statistically significant increase in platelet counts and also reduced bleeding in adult patients with chronic idiopathic thrombocytopenia purpura (ITP). These patients had previously received and failed current standard ITP treatments. These data, which are part of a six-week study of eltrombopag in patients with chronic ITP, were presented at the 12th congress of the European Haematology Association (EHA) in Vienna, Austria.

"ITP is a condition that can be serious for some individuals, or those who fail to respond to therapy and not only puts patients at risk of bleeding but may also cause severe fatigue, bruises and complications during surgery or pregnancy," says Dr Drew Provan, senior lecturer in Haematology, Department of Haematology, Royal London Hospital, UK and investigator for this trial. "Options are particularly limited for those patients who fail to respond to primary treatment altogether and those who initially respond and then fail. These trial results demonstrate that eltrombopag may represent the potential for a new oral therapy to reduce the number of bleeding episodes in ITP patients."

There are estimated to be between 50,000-100,000 individuals diagnosed with chronic ITP in the US People with ITP often bleed from small blood vessels causing bruises, nosebleeds, bleeding from the gums during dental work, or other bleeding that is difficult to stop. The predicted five year mortality rates for ITP patients with persistent low platelet counts range from 2.2 per cent for patients younger than 40 years of age, to 47.8 per cent for those older than 60 years.

The phase III trial was an international, randomised, double-blind, placebo-controlled study that enrolled 114 adults with chronic ITP and baseline platelet counts of <30,000/µL. Eligible patients must have failed or stopped responding within three months of receiving one or more ITP therapies such as corticosteroids, immunoglobulins and/or splenectomy. Patients were allowed to continue on a concomitant ITP medication, provided their dose had been stable for at least a month prior to enrolment. These patients were randomised to either placebo (38 patients) or eltrombopag 50mg (76 patients) once daily for six weeks. The eltrombopag dose could be increased to 75mg in patients not responding after an initial three weeks of treatment. Patients were assessed for platelet count weekly and up to six weeks following treatment with eltrombopag. Bleeding events were assessed weekly using the World Health Organization (WHO) bleeding scale.

At the end of the trial, 59 per cent of eltrombopag treated patients and 16 per cent of placebo treated patients achieved a platelet count of more than 50,000/µL. Importantly, there was a significantly lower incidence of bleeding events during treatment with eltrombopag compared to placebo with clinically significant bleeding (WHO Grades 2-4) observed in fewer eltrombopag patients (16%) than placebo patients (36%). The most common adverse event (AE) observed in this study was headache, reported in 8 per cent and 11 per cent of patients receiving eltrombopag and placebo respectively. Other AEs included nausea, nasopharyngitis, diarrhoea and vomiting.

"We are extremely encouraged by these eltrombopag results, and what this may mean for ITP patients," said Paolo Paoletti, MD, senior vice president, Oncology Medicine Development Centre, GSK. "This pivotal phase III trial data and our ongoing efforts to assess the benefits of both short- and long-term treatment of eltrombopag will be part of GSK's commitment to work with regulatory authorities and ensure new treatment options for ITP patients are provided."