GSK initiates repeat dosing study of its novel oral platelet growth factor, eltrombopag, in ITP
Issued — Thursday 12 April 2007, London, UK & Philadelphia, US
GlaxoSmithKline plc today announced the initiation of a global, open-label, single group trial that will assess the efficacy, safety and tolerability of eltrombopag in patients previously treated for chronic idiopathic thrombocytopenic purpura (ITP). The trial, called REPEAT (Repeat ExPosure to Eltrombopag in Adults with Idiopathic Thrombocytopenic Purpura) will evaluate a repeated dosing schedule of three six week cycles of eltrombopag treatment in 50 patients with chronic ITP who will be enrolled at multiple centres.
"The current treatment approaches to acutely increase the platelet count typically include treatment with steroids or IV gammaglobulin - both of which may have issues with tolerability or safety,” 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 investigator for this trial. "Due to patients'' varying clinical circumstances, it is important to validate the safety and effectiveness of repeated short-term treatment with eltrombopag in patients with chronic ITP."
ITP is estimated to affect 50 to 100 new persons per million per year in the United States and Europe.1 People with ITP often bleed from small blood vessels underneath the skin causing bruises, nosebleeds, bleeding from the gums during dental work, or other bleeding that is difficult to stop. Bleeding in the brain or gastrointestinal (GI) tract is rare but can be life threatening if it occurs.2 Although this condition can be managed chronically, it is associated with significant mortality and morbidity — 5% of patients will die within ten years of diagnosis, primarily from intracranial haemorrhage.3
Initiation of the REPEAT trial follows completion of studies that evaluated 231 patients with chronic ITP and low platelet levels (<30,000/µL).3 The results showed a statistically significant increase (p=0.001) in the number of patients achieving a platelet count to ≥50,000/µL and decreased bleeding following eltrombopag doses of >50mg over six weeks.3 Eltrombopag was not associated with an increased incidence of adverse events (AEs) compared to placebo across the 30mg, 50mg and 75mg eltrombopag treatment arms. Bleeding adverse events included the following:haemorrhoids,haemorrhagic diarrhoea and conjunctival haemorrhage in 3 patients receiving placebo; epistaxis, gingival bleeding and contusions in 5 patients receiving 30mg of eltrombopag; menorrhagiain 1 patient receiving 50mg of eltrombopag (who did not respond to eltrombopag); and contusion in 1 patient receiving 75mg of eltrombopag. All seven patients who received eltrombopag and bled were non-responders. The most common AE observed in this study was mild to moderate headache, reported in 21% of subjects on placebo, and 13%, 10% and 21% of subjects in the 30mg, 50mg and 75mg eltrombopag arms, respectively.3
“We are extremely encouraged by the continued progress in our eltrombopag clinical development programme”, said Paolo Paoletti, MD, Senior Vice President, Oncology Medicine Development Centre, GSK. “We continue to be very optimistic about eltrombopag and we expect results from this trial will represent another step towards providing patients with a safer, more effective ITP treatment.”
In December 2006, GlaxoSmithKline announced the initiation of a Phase III trial assessing the safety, efficacy and tolerability of eltrombopag in a long-term setting (up to six months) in patients previously treated for chronic ITP. Long-term ITP treatment may be necessary in patients with consistently low platelet levels and current treatment options such as steroids have draw-backs if used on a long-term basis. Therefore, it is important to evaluate eltrombopag in this setting.4
Results from other studies involving eltrombopag will be presented at international medical congresses in the near future, and additional studies are ongoing and planned in ITP and other conditions where thrombocytopenia is an issue. Eltrombopag is an investigational agent that is not approved for use in any market for any indication at this time.
Study design
The REPEAT trial will assess the efficacy, safety, and tolerability of three repeated dosing cycles of eltrombopag in patients previously treated for chronic ITP, examples of which include splenectomy, corticosteroids, immunoglobulins, cyclophosphamide and rituximab. The primary objective is to evaluate the effect of eltrombopag on platelet counts during three consecutive treatment cycles with eltrombopag. Secondary objectives include evaluating incidence and severity of bleeding, as well as the frequency of adverse events.
About eltrombopag
Eltrombopag is a 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 maybe considered a platelet growth factor. Eltrombopag reduces the risk of bleeding and bruising in patients with ITP by elevating and maintaining platelet levels >50,000/µL.3 Eltrombopag is administered orally as a once a day tablet. The safety profile will be further examined in the ongoing clinical trials. Eltrombopag was discovered as a result of a 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.
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 mucosal bleeding that can become severe.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 and diagnosis can be confirmed following a routine blood test.
Other forms of thrombocytopenia
Thrombocytopenia can occur as a consequence of an autoimmune abnormality, a bone marrow disease, chemotherapy treatment, interferon treatment, viral infection or chronic liver disease. Thrombocytopenia can impede a variety of medical treatments. It can prevent cancer patients from receiving their full dose of chemotherapy, preclude patients with hepatitis C infection from receiving interferon therapy or lead to dose reductions or discontinuation, and complicate surgical or dental procedures.
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.
For further information on the trial please visit www.itpstudy.com or www.clinicaltrials.gov.
Notes to editors
To access the latest GSK Oncology media materials, visit www.gskcancermedia.com
References
1 National Heart, Lung, and Blood Institute. Diseases and Conditions Index. www.nhlbi.nih.gov/health/dci/Diseases/Itp/ITP_Summary.html. Accessed Mar 15 2007.
2 Newland, A, Cheng, G, et al. Eltrombopag increases platelets during 6-week treatment of ITP - results of a randomized, double-blind, placebo-controlled phase II study. Presented 18 June 2006, 11th Congress of the European Hematology Association meeting, Amsterdam, the Netherlands
3 Bussel, J., Cheng, G. et al. Eltrombopag, an Oral Platelet Growth Factor, for Treatment of Chronic Immune Thrombocytopenic Purpura (ITP): A Randomized, Double-blind, Placebo-controlled Trial. Presented 11 December 2006, 47th Annual Meeting of the American Society of Hematology, Orlando, Florida, USA.
4 Cines D.B., and Blanchette, V.S. (2002) Immune thrombocytopenic purpura. N Engl J Med. 346:995-1008.
5 Stasi, R., Provan, D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004;79:504- 522.
6 Medline Plus. Medical Encyclopedia. www.nlm.nih.gov/medlineplus/ency/article/003647.htm. Accessed Mar 15 2007.
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