Pivotal Phase III Trial Showed Promacta (eltrombopag olamine) Raised Platelet Counts and Reduced Bleeding in Patients With Chronic ITP

VIENNA, Austria, June 11, 2007 /PRNewswire/ -- GlaxoSmithKline plc announced results from an international, pivotal Phase III study of its investigational non-peptide oral platelet growth factor, PROMACTA(R) (eltrombopag olamine). Data from this study showed that PROMACTA at 50-75mg once daily resulted in a statistically significant increase in platelet counts and also reduced bleeding in adult patients with chronic idiopathic thrombocytopenic purpura (ITP). These patients had previously received and failed current standard ITP treatments. These data, which are part of a six-week study of PROMACTA in patients with chronic ITP, were presented at the 12th 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 Drew Provan, M.D., Senior Lecturer in Hematology, Department of Hematology, Royal London Hospital, U.K. 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 PROMACTA 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. In Europe, primary ITP is estimated to affect 50 to 100 new persons per million per year.(2) 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.(3)

"We are extremely encouraged by these PROMACTA results, and what this may mean for ITP patients," said Paolo Paoletti, M.D., Senior Vice President, Oncology Medicine Development Center, GSK. "This pivotal Phase III trial data and our ongoing efforts to assess the benefits of both short- and long-term treatment of PROMACTA will be part of GSK's commitment to work with regulatory authorities and ensure new treatment options for ITP patients are provided."

The Phase III trial was an international, randomized, double-blind, placebo-controlled study that enrolled 114 adults with chronic ITP and baseline platelet counts of <30,000/microliter. 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 randomized to either placebo (38 patients) or PROMACTA 50mg (76 patients) once daily for six weeks. The PROMACTA 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 PROMACTA. Bleeding events were assessed weekly using the World Health Organization (WHO) bleeding scale.(1)

At the end of the trial, 59% of PROMACTA treated patients and 16% of placebo treated patients achieved a platelet count of more than 50,000/microliter. Importantly, there was a significantly lower incidence of bleeding events during treatment with PROMACTA compared to placebo (p=0.029) with clinically significant bleeding (WHO Grades 2-4) observed in fewer PROMACTA 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 PROMACTA and placebo respectively. Other AEs included nausea, nasopharyngitis, diarrhea and vomiting.

About PROMACTA

PROMACTA (eltrombopag olamine) 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.(4) The safety profile will be further examined in ongoing clinical trials. PROMACTA was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by GlaxoSmithKline. PROMACTA is an investigational compound that has not received regulatory approval in any market for any indication at this time.

Ongoing Trials

Several PROMACTA trials investigating the short- and long-term treatment of chronic ITP are currently open and enrolling.(5) EXTEND (Eltrombopag eXTENded Dosing Study) is an open-label study for patients who had participated in previous PROMACTA trials and wished to take PROMACTA for the long-term treatment of their chronic ITP. RAISE (RAndomized placebo controlled ITP Study with Eltrombopag) is a global, randomized, double-blind, placebo-controlled Phase III trial currently assessing the safety, efficacy and tolerability of PROMACTA in a long-term treatment setting (up to six months) involving 189 patients across 135 centers 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 PROMACTA. For further information on the trials, visit http://www.itpstudy.com or http://www.clinicaltrials.gov.

About Idiopathic Thrombocytopenic Purpura

ITP is characterized 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.(6) A normal blood platelet count is greater than or equal to 150,000/microliter and less than or equal to 400,000/microliter.(7) A reduction in platelet count (to a level <150,000/microliter) is the defining characteristic of any type of thrombocytopenia which can be confirmed following a routine blood test. An endpoint of 50,000/microliter was selected because at a platelet count of <50,000/microliter there is a higher risk of developing bleeding complications from low platelet counts. At a platelet count of >50,000/microliter 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.(8)

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.(9,10) 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.(11,12)

About GlaxoSmithKline

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

For further information on trials please visit http://www.itpstudy.com or http://www.clinicaltrials.gov.

Notes to Editors

PROMACTA(R) is the proposed registered trademark of the GlaxoSmithKline group of companies to be used in the United States.

    To access the latest GSK news, visit http://us.gsk.com/.



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    REFERENCES


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         Short-term Treatment in Chronic Idiopathic Thrombocytopenic Purpura:

         A Phase III Study. Presented 9th June 2007, 12th Congress of the

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    (2)  Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic

         purpura. Annu Rev Med. 2005;56:425-442.

    (3)  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.

    (4)  Bussel, J., Cheng, G. et al.  Analysis of Bleeding in Patients with

         Immune Thrombocytopenic Purpura (ITP): A Randomized, Double-Blind,

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         - Abstract #475.

    (5)  http://clinicaltrials.gov/ct/search;jsessionid=

         F4C94197494A9A19BE7A77071F71ECA2?term=eltrombopag.  Accessed April 16

         2007.

    (6)  Stasi, R., Provan, D. Management of immune thrombocytopenic purpura

         in adults. Mayo Clin Proc. 2004;79:504- 522.

    (7)  http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm.  Accessed

         Oct 19 2006.

    (8)  Study TRA100773 protocol

    (9)  http://www.mayoclinic.com/health/thrombocytopenia/DS00691/DSECTION=3.

         Accessed April 16 2007.

    (10) http://www.netdoctor.co.uk/diseases/facts/thrombocytopenia.htm.

         Accessed April 16 2007.

    (11) Goodnough LT, DiPersion JF.  Issues in the management of cancer-

         related thrombocytopenia.  Oncology. 2002; 16(11):1558-67.

    (12) Ong, JP., Younossi ZM. Managing the hematologic side effects of

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         thrombocytopenia. Cleve Clin J Med. 2004;71:S17-21.

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Posted: June 2007

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