Press Release

Once-a-day, oral therapy with a unique mode of action that stimulates platelet production and reduces the risk of bleeding during treatment

GlaxoSmithKline (GSK) announced today that the European Medicines Agency (EMEA) has granted marketing authorisation for Revolade® (eltrombopag), a once-daily oral treatment for adults with chronic immune thrombocytopenic purpura (ITP).1 Revolade is for patients who have already had their spleen removed (splenectomy) and are not responding to other treatments such as corticosteroids and immunoglobulins. It may also be considered as second line treatment for adult non-splenectomised patients where surgery is contraindicated. 1 ITP is a blood disorder characterised by a low platelet count and excessive bleeding.2

Revolade belongs to a class of agents known as thrombopoietin receptor agonists (TRAs) and is the first oral TRA licensed for this patient group. It has a unique mode of action which increases platelet production; this is a different therapeutic approach to existing ITP treatments such as immunoglobulins and corticosteroids, which reduce platelet destruction. 3 4, 5, 6

From a randomised placebo-controlled ITP study (RAISE TRA102537), the odds of responding over the 6-month treatment period were 8 times greater in Revolade-treated subjects than in placebo-treated subjects (p<0.001).7 Furthermore, throughout the entire treatment period, the odds of any bleeding (WHO Bleeding Grade 1-4) were significantly lower in subjects treated with Revolade compared to those treated with placebo (p<0.001).7

Dr Drew Provan, Senior Lecturer in Haematology, Barts and The London of School of Medicine and Dentistry commented: “Eltrombopag, as a once-a-day tablet, represents an innovative step forward in helping patients and their physicians meet the challenges of managing chronic ITP. Eltrombopag is an effective drug which is easy to take, offering a reduced risk of bleeding during treatment as well as broadening the options available to chronic ITP patients.”

Chronic ITP is a serious condition, where patients have low platelet levels either because the body does not produce enough platelets or destroys too many.2, 8 Platelets are essential to normal clotting, so patients with ITP are at increased risk of bleeding and for example may develop bruises or experience nose or gum bleeds or other types of bleeding that are difficult to stop.9, 10 Although a very rare occurrence, bleeding in the brain, associated with ITP, is potentially fatal9.

Revolade Data
Marketing authorisation for Revolade is based on the results from two Phase III, randomised, double-blind, placebo-controlled clinical trials, TRA100773B6 and RAISE TRA102537,7 and two open-label studies, REPEAT TRA 10805711 and EXTEND TRA105325,3 in previously-treated adult chronic ITP patients.

These studies showed that the patients treated with Revolade (plus the standard of care) experienced significant increases in platelet counts and a reduction in the incidence of bleeding, compared to those taking placebo (plus the standard of care).3, 6,7 Revolade treatment also allowed patients to reduce the dose of their concomitant medications, such as steroids.7

Revolade was generally well tolerated in ITP studies.1 In some cases, nausea, vomiting and abnormal liver function were recorded in the Revolade group and not in the placebo group.6

No clinically significant findings have been noted to date with bone marrow fibrosis, post-therapy reoccurrence of thrombocytopenia or cataracts although regular monitoring of platelet counts, liver function and the potential impact on bone marrow and cataracts is recommended.

In the UK, the crude incidence of adult ITP is 3.9 per 100,000 persons per year.12 Quality of life is adversely affected in patients with chronic ITP, with a fear of bleeding considerably limiting patients’ daily activities, such as participating in sports or manual work.13, 14 Fatigue and depression are also often associated with ITP.15

References

1. Revolade? Summary Of Product Characteristics (SPC). GlaxoSmithKline, February 2010.

2. Cines D, Blanchette V, Chir B. Immune Thrombocytopenic Purpura. New England Journal of Medicine. 2002; 346:995-1008.

3. Saleh M, Bussel JB, Cheng G, et al. Eltrombopag is efficacious in patients with refractory chronic idiopathic thrombocytopenic purpura (ITP) – data from the EXTEND Study. Blood 2008; 112:401 [ASH Annual Meeting Abstracts].

4. Stasi R, Provan D. Management of Immune Thrombocytopenic Purpura in Adults. Mayo Clin Proc. 2004;79:504-522.

5. McMillan R, Durette C. Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood. 2004;104: 956-960.

6. Bussel JB, Provan D, Shamsi T, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373:641-8.

7. Cheng G, Saleh M, Bussel J, et al. Oral eltrombopag for the long-term treatment of patients with chronic idiopathic thrombocytopenic purpura: results of a Phase III, double-blind, placebo-controlled study (RAISE). Blood 2008; 112:400. [ASH Annual Meeting Abstracts].

8. National Library of Medicine. Medical Encyclopedia – Platelet Count. http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm (accessed 11 November 2009).

9. National Heart, Lung, and Blood Institute: ITP 2009.
http://www.nhlbi.nih.gov/health/dci/Diseases/Itp/ITP_All.html

10. Platelet Disorder Support Association (PDSA): About ITP http://www.pdsa.org/about-itp.html

11. Psaila B, Bussel J, Vasey S, et al. Efficacy and safety of repeated intermittent treatment with eltrombopag in patients with chronic ITP. Abstract 0294 presented at the 13th congress of the European Haematology Association, June 2008.

12. Abrahamson P, Hall S, Feudjo-Tepie M, et al. The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review. Eur J Haem 2009; 83: 83-89

13. Mathias SD, Gao SK, Miller KL, et al. Impact of chronic immune thrombocytopenic purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective. Health Qual Life Outcomes 2008; 6:13.

14. Michel M. Immune thrombocytopenic purpura: epidemiology and implications for patients. Eur J Haem 2009; 82 (suppl. 71), 3-7

15. Platelet Disorder Support Association (PDSA): ITP Information. http://www.pdsa.org/itp-information/index.html Accessed November 2009.

16. Stasi R. Immune thrombocytopenic purpura: the treatment paradigm. Eur J Haem 2009; 82 (suppl. 71): 13-19.

17. Nurden AT, Viallard J-F, Nurden P. New-generation drugs that stimulate platelet production in chronic immune thrombocytopenic purpura. Lancet ; published online 25 March 2009.

18. EMEA. Committee for Orphan Medicinal Products. Public summary of positive opinion for orphan designation of eltrombopag olamine for the treatment of idiopathic thrombocytopenic purpura, 2009:1-4.

For more information:
http://www.gsk.com

Last updated on: 27/08/2010 11:40:18