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Embargoed until Saturday 9 June 2007, 08.00am BST

GlaxoSmithKline plc today 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 today at the 12^th congress of the European Hematology Association (EHA) in Vienna, Austria.[1]

"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 U.S. 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% for patients younger than 40 years of age, to 47.8% for those older than 60 years.[2]

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 enrollment. 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.¹

At the end of the trial, 59% of eltrombopag treated patients and 16% 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 (p=0.029) 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% and 11% 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.”

About eltrombopag

Eltrombopag is an oral, non-peptide 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 can be considered a platelet growth factor.[3] The safety profile will be further examined in ongoing clinical trials. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by GlaxoSmithKline. Eltrombopag is an investigational compound that has not received regulatory approval in any market for any indication at this time.

Ongoing trials

Several eltrombopag trials investigating the short- and long-term treatment of chronic ITP are currently open and enrolling.^[4] EXTEND (Eltrombopag eXTENded Dosing Study) is an open-label study for patients who had participated in previous eltrombopag trials and wished to take eltrombopag for the long-term treatment of their chronic ITP. RAISE (RAndomised placebo controlled ITP Study with Eltrombopag) is a global, randomised, double-blind, placebo-controlled Phase III trial currently assessing the safety, efficacy and tolerability of eltrombopag in a long-term treatment setting (up to six months) involving 189 patients across 135 centres in 26 countries. REPEAT (Repeat ExPosure to Eltrombopag in Adults with Idiopathic Thrombocytopenic Purpura) will involve 50 patients with chronic ITP and will assess the safety and efficacy of repeated administration of eltrombopag.

For further information on the trials please visit www.itpstudy.com or www.clinicaltrials.gov.

About Idiopathic Thrombocytopenic Purpura

ITP is characterised by increased autoimmune platelet destruction and/or inadequate platelet production. Its cause is currently unknown. Some patients with ITP are asymptomatic or have mild bruising while others develop more serious bleeding that can be life-threatening.^[5] A normal blood platelet count is ≥150,000/µL and ≤400,000/µL.^[6] A reduction in platelet count (to a level <150,000/µL) is the defining characteristic of any type of thrombocytopenia which can be confirmed following a routine blood test. An endpoint of 50,000/µL was selected because at a platelet count of less than 50,000/µL there is a higher risk of developing bleeding complications from low platelet counts. At a platelet count of >50,000/µL there is a lower risk of bleeding and bruising. This is consistent with products previously approved to treat ITP and is considered as a target platelet count in ITP treatment guidelines.[7]

Other forms of thrombocytopenia

Thrombocytopenia can occur as a consequence of an autoimmune abnormality, bone marrow insufficiency, chemotherapy treatment, interferon treatment, viral infection or chronic liver disease.[8]^,[9] Thrombocytopenia can impede a variety of diagnostic and/or medical treatments. It can prevent cancer patients from receiving their full dose of chemotherapy on schedule, preclude patients with hepatitis C infection from receiving interferon therapy or lead to dose reductions or discontinuation of therapy, and complicate surgical or dental procedures.^3,[10],[11]

About GlaxoSmithKline

GlaxoSmithKline is one of the world’s leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit www.gsk.com.

Notes to editors

REVOLADE^® and PROMACTA^® are registered trade marks of the GlaxoSmithKline group of companies.

PROMACTA^® is the proposed registered trademark to be used in the United States.

REVOLADEäis the proposed trade mark for use in certain European countries.

To access the latest GSK Oncology media materials, visit www.gskcancermedia.com.

Enquiries:

 

UK Media enquiries:	Philip Thomson	(020) 8047 5502
	Joss Mathieson	(020) 8047 5502
	Gwenan White	(020) 8047 5502
European Analyst/Investor enquiries:	Anita Kidgell	(020) 8047 5542
	David Mawdsley	(020) 8047 5564
	Sally Ferguson	(020) 8047 5543

REFERENCES

[1] Bussel, J., Provan A., Shamsi T et al. Eltrombopag Raises Platelet Count and Reduces Bleeding compared with Placebo during

Short-term Treatment in Chronic Idiopathic Thrombocytopenic Purpura: A Phase III Study. Presented 9th June 2007, 12^th Congress of the European Hematology Association, Vienna, Austria. Abstract # 1814.

[2] Cohen, YC., Djulbegovic B., et al. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Int Med. 2000:160 (11);1630-8.

[3] Bussel, J., Cheng, G. et al. Analysis of Bleeding in Patients with Immune Thrombocytopenic Purpura (ITP): A Randomized, Double-Blind, Placebo-Controlled Trial of Eltrombopag, an Oral Platelet Growth Factor. Presented 11 December 2006, 48^th Annual Meeting of the American Society of Hematology, Orlando, Florida, USA– Abstract # 475.

[4] http://clinicaltrials.gov/ . Accessed April 16 2007.

[5] Stasi, R., Provan, D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004;79:504- 522.

[6] www.nlm.nih.gov/medlineplus/ency/article/003647.htm . Accessed Oct 19 2006.

[7] Study TRA100773 protocol.

[8] www.mayoclinic.com/health/thrombocytopenia/DS00691/DSECTION=3 . Accessed April 16 2007.

[9] www.netdoctor.co.uk/diseases/facts/thrombocytopenia.htm . April 16 2007.

[10] Goodnough LT, DiPersion JF. Issues in the management of cancer-related thrombocytopenia. Oncology. 2002; 16(11):1558-67.

[11] Ong, JP., Younossi ZM. Managing the hematologic side effects of antiviral therapy for chronic hepatitis C: anemia, neutropenia, and thrombocytopenia. Cleve Clin J Med. 2004;71:S17-21.