GlaxoSmithKline plc announced results from a global phase II study of its investigational small molecule oral platelet growth factor, eltrombopag. Data from this study demonstrated that treatment with eltrombopag resulted in a significant increase in platelet count compared to placebo across a variety of typically poorly responding ITP patients including those with prior splenectomy or those having a very low baseline platelet count (<15,000/mL).

At doses of 50mg and 75mg, 70 per cent and 81 per cent of patients respectively, achieved the primary clinical endpoint of having a platelet count greater than 50,000/mL after up to 6 weeks of dosing compared to 11 per cent of patients on placebo.1 Full results from this randomized, double-blind, placebo-controlled trial are being presented today at the 11th Annual Congress of the European Haematology Association (EHA) in Amsterdam. Based on these and previous clinical trial results, eltrombopag has the potential to be the first oral platelet growth factor for patients with thrombocytopenia, a disorder characterized by low platelet counts leaving patients at risk of episodes of spontaneous bruising, mucosal bleeding, and in severe cases intracranial haemorrhage.

"Results demonstrating the beneficial effect of an oral therapy such as eltrombopag, which may potentially work by stimulating the production of platelets, is very exciting and a major scientific advance," says Adrian Newland, Professor of Haematology at Queen Mary, University of London and a principal investigator for this trial. "This is highly encouraging news for patients who are in real need of new therapies to combat ITP because current treatment options such as steroids or removal of the spleen all have significant limitations, particularly in terms of side effects."

Eltrombopag is an investigational non-peptide small molecule that is administered orally and interacts with the thrombopoietin receptor. This receptor is located on the surface of specific cells in the bone marrow and its stimulation leads to the production of platelets.

The global phase II trial enrolled 118 adult patients with chronic idiopathic thrombocytopenic purpura (ITP). Patients were permitted to continue receiving stable doses of maintenance immunosuppressive therapy while participating in the study. Baseline platelet counts were <30,000/mL and the primary efficacy endpoint was the proportion of patients with platelets ?50,000/mL after up to 6 weeks of dosing. A dose dependent increase in the proportion of responders was observed: placebo (11%), 30mg (28%), 50mg (70%) and 75mg (81%).1 Difficult to treat subgroups including patients with previous splenectomy, patients who did not respond to previous treatments and patients with very low platelet counts (<15,000/mL) showed response to treatment with eltrombopag.

Overall, the safety profile was similar across the treatment groups, with the following percentage of patients experiencing at least one adverse event (AE) during treatment: placebo (59%), 30mg (47%), 50mg (47%) and 75mg (61%). The most common AE in the eltrombopag 75mg arm was headache reported by 21% of patients; 21% of patients exposed to placebo also reported headache. A total of 3 (10%), 2 (7%) and 1 (4%) of patients in the placebo, 50 mg and 75 mg groups respectively experienced an AE leading to withdrawal during treatment. No patients in the 30mg eltrombopag arms withdrew from the trial due to adverse events. No dose dependent safety concerns were identified.

"ITP is a frightening disease which does not follow a predictable course. Severity and symptoms vary enormously from one patient to another," says Shirley Watson, Founder of the ITP Support Association. "It is exciting news that a new drug is in development for ITP sufferers whose condition requires treatment. As eltrombopag stimulates platelet production rather than preventing platelet destruction, it offers a different approach for those with chronic refractory ITP."

Also during the EHA, Joseph A Erhardt of GlaxoSmithKline gave an oral presentation of data (abstract 1024) showing that in vitro stimulation of platelet production by eltrombopag induces the same level of platelet function as those produced in vivo.

"As we move into Phase III studies, the development of eltrombopag treatment represents a significant milestone for GSK Oncology in supportive care and underscores our continued commitment to delivering novel treatments to potentially meet a significant unmet medical need," says Paolo Paoletti, MD, Senior Vice President, Oncology Medicine Development Centre, GSK.

Eltrombopag is an investigational small-molecule thrombopoietin receptor agonist that has been shown in pre-clinical research and clinical trials to stimulate the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets, and thus may be considered a platelet growth factor. Because it is a small molecule, eltrombopag is administered orally as a tablet and may have less potential than large protein molecules for causing an immune system reaction.

Eltrombopag was discovered as a result of a research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by GlaxoSmithKline.

A reduction in platelet count is the defining characteristic of any type of thrombocytopenia and diagnosis can be confirmed following a routine blood test. Thrombocytopenia occurs in 5% to 10% of all patients hospitalized for any cause.

Idiopathic thrombocytopenic purpura is an autoimmune disorder that is marked by platelet destruction and/or inadequate platelet production. Primary ITP is estimated to affect 50 to 100 new persons per million per year in the United States and Europe.4 Some patients with ITP are asymptomatic or have mild bruising while others develop mucosal bleeding that can become severe.5 ITP is associated with a 5% fatality rate largely due to intracranial hemorrage.

Thrombocytopenia also can occur as a consequence of chemotherapy treatment, interferon treatment, or chronic liver disease. Thrombocytopenia can impede a variety of medical treatments. It can prevent cancer patients from receiving their full dose of chemotherapy, prevent patients with hepatitis C infection from receiving interferon therapy or lead to dose reductions or discontinuation, and it can prevent or complicate procedures (surgical, dental etc.) in patients with chronic liver disease and ITP.