Positive results with Revolade™ and Arzerra™ for difficult-to-treat blood disorders

GlaxoSmithKline (GSK) Oncology today announced further encouraging data for their investigational products Revolade™ (eltrombopag) and Arzerra™ (ofatumumab) at the 14th Congress of European Hematology meeting, organised by The European Hematology Association (EHA). The results demonstrate the potential of these drugs to improve patient outcomes and quality of life (QoL) in two haematological conditions.

Issued: Friday, 5 June 2009, London UK

GlaxoSmithKline (GSK) Oncology today announced further encouraging data for their investigational products Revolade (eltrombopag) and Arzerra (ofatumumab) at the 14th Congress of European Hematology meeting, organised by The European Hematology Association (EHA). The results demonstrate the potential of these drugs to improve patient outcomes and quality of life (QoL) in two haematological conditions.

GSK data being presented at the 2009 EHA Congress include new Phase III results for eltrombopag for a blood disorder known as chronic idiopathic thrombocytopenic purpura (ITP) and updated analyses of the pivotal study results for ofatumumab for late-stage chronic lymphocytic leukaemia (CLL).

“We are proud to develop medicines that may improve patients’ lives across the full spectrum of blood cancers and disorders,” said Michael Arning, M.D., Vice President, Oncology Medicine Development Center, GSK. “The submission of eltrombopag and ofatumumab to the European Medicines Agency for regulatory review in December 2008 and February 2009 respectively, demonstrate our commitment to patients to provide innovative medicines for these diseases.”

ORAL PRESENTATION: Association of Health-Related Quality of Life (HRQOL), Bleeding, and Platelet Levels in Chronic Idiopathic Thrombocytopenic Purpura (ITP): Results from RAISE and EXTEND (Abstract #1058) Embargo lifted Sunday 7 June 2009, 08.45 CEST

New data from two long-term studies (RAISE – 197 patients and EXTEND – 144 patients) show that patients treated with eltrombopag experienced significant elevations in platelet counts, as well as a reduction in bleeding and bruising, compared with placebo. In addition, patients experienced a statistically significant improvement in QoL. [i] QoL assessments measured patients’ vitality, fatigue, their ability to participate in normal day-to-day physical and social activities, as well as concerns related to bleeding and bruising.1 

“In two studies, we see the ability of eltrombopag, given once a day as an oral tablet, to increase platelet counts, reduce bleeding, and improve patient quality of life,” said Professor Adrian Newland, Professor of Haematology, The Royal London Hospital, London, U.K. “As physicians, we are primarily concerned with treating the disease, but it is also very important to establish the day-to-day impact of any potential medication. These data show how the clinical benefits achieved with eltrombopag equate to improvements in quality of life for ITP patients."

ITP is characterised by a low platelet count [ii] and an increased risk of bleeding2. Patients with ITP frequently suffer from bruises, nosebleeds, or bleeding that is difficult to stop.2Bleeding in the brain or gastrointestinal tract is less frequent, but can be life-threatening.2 Fear of bleeding can limit a patient’s everyday activities and impact their QoL.[iii]

In previous studies, the most common side-effects reported with eltrombopag use are nausea and diarrhoea. All other reported adverse events were similar between eltrombopag and placebo. [iv],[v]

ORAL PRESENTATION: Single-Agent Ofatumumab, a Novel CD20 Monoclonal Antibody, Results in High Response Rates in Patients with Fludarabine-Refractory CLL also Refractory to Alemtuzumab or with Bulky Lymphadenopathy (Abstract #0494)

Embargo lifted Saturday 6 June 2009, 08.45 CEST

Patients in this study were heavily pre-treated CLL patients who did not respond to, or who were ineligible for, currently available treatment options such as fludarabine and alemtuzumab. [vi]  

Based on an assessment from an independent endpoint review committee, ofatumumab demonstrated a 58 percent response rate in patients resistant to fludarabine and alemtuzumab (FA-ref). In those patients who did not respond to fludarabine and were not suitable for alemtuzumab (BF-ref), ofatumumab demonstrated a 47 percent response rate.6

“This analysis shows that ofatumumab delivered a significant improvement in disease symptoms and survival for patients with advanced-stage, difficult-to-treat CLL,” said Primary Investigator, Professor Anders Österborg, Department of Hematology, Karolinska Hospital, Stockholm, Sweden. “Typically, these types of advanced CLL patients are known to experience very poor outcomes, and at the moment there is no approved treatment for them. The response rate and tolerability profile of ofatumumab in this study are very encouraging.”

Study results showed that ofatumumab treatment demonstrated no unexpected adverse events. Infusion reactions at the first dose were seen in 38 percent of patients but these diminished over the course of the treatment.6 The most common grade three or four related adverse events during the treatment period were infections and neutropenia (low white blood cells).6 Early death (<8 weeks from="" treatment="" initiation) occurred in="" four="" fa-ref and="" two bf-ref patients none of="" which were considered related to="">6

Globally, 300,000 new cases of leukaemia are diagnosed each year and 222,000 patients lose their lives. [vii] CLL is the most common form of leukaemia in adults in western countries, accounting for 25 percent of all leukaemias. [viii],[ix] The annual incidence rate is projected to be between <1 and="" 5.5 per 100,000=""> [x] However, this figure is much higher in those over 70 years of age with an annual incidence rate of 50 cases per 100,000. [xi] The specific patient population that ofatumumab is being investigated for are CLL patients who have progressed following treatment with multiple therapies; this is a small, difficult-to-treat patient population.

NOTES TO EDITORS

Eltrombopag

Eltrombopag, which works by stimulating platelet production, is the first oral treatment for patients with previously treated chronic ITP. [xii]  

Eltrombopag is an investigational compound which has not received regulatory approval outside of the US and Venezuela, for any indication, at this time. Eltrombopag was submitted to the European Medicines Agency (EMEA) for regulatory review in December 2008 under the trade name Revolade. Eltrombopag was granted accelerated approved by the U.S. Food and Drug Administration (FDA) under the trade name Promacta® in November 2008 for the treatment of chronic ITP. 

Thrombopoietin (TPO) is the body’s platelet growth factor, a specific type of blood cell that stimulates the bone marrow to make platelets. [xiii],[xiv] Eltrombopag helps to increase platelet levels by binding to the TPO receptor on cells in the bone marrow. [xv] Eltrombopag is currently being studied in other areas where thrombocytopenia can interfere with treatments (e.g. hepatitis C, chronic liver disease and cancer). The discovery of eltrombopag resulted from a research collaboration between GSK and Ligand Pharmaceuticals, and was developed by GSK.

Ofatumumab

Ofatumumab (HuMax-CD20) is a novel, fully human-derived, investigational monoclonal antibody (MAb).[xvi] MAbs are designed to bind to and act against a single specific antigen.[xvii]. Ofatumumab binds to a specific part of the CD20 protein on the surface of B cells, known as the small loop epitope, which recruits components of the body’s immune system to attack and destroy those cells.16 The ofatumumab binding site on CD20 differs from the binding site of other currently approved CD20 MAbs, such as rituximab.[xviii] Ofatumumab is being developed to treat CLL, follicular lymphoma, diffuse large B cell lymphoma, Waldenstrom’s macroglobulinemia, rheumatoid arthritis and relapsing-remitting multiple sclerosis under a co-development and commercialisation agreement between Genmab and GSK.

Ofatumumab was submitted to the EMEA for regulatory review in February 2009 and to the U.S. FDA in January 2009. Ofatumumab is an investigational compound which has not yet received regulatory approval for any indication, in any country, at this time.

GSK in Oncology

GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s revolutionary ‘bench to bedside’ approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes collaborations with more than 160 cancer centres. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.

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 further information please visit www.gsk.com

Revolade is a registered trademark of GlaxoSmithKline group of companies and the proposed trade name in Europe.

Promacta® is a registered trademark of GlaxoSmithKline group of companies in the United States.

Arzerra™ is a registered trademark of GlaxoSmithKline group of companies and the proposed trade name in the United States and Europe.

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

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[i]       Bussel J, Grotzinger K, Duh M, et al. Association of Health-Related Quality of Life (HRQOL), Bleeding, and Platelet Levels in Chronic Idiopathic Thrombocytopenic Purpura (ITP): Results from RAISE and EXTEND. Presented at the 14th EHA meeting, 2009. Abstract# 1058

[iii]     MathiasSD, GaoSK, 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

[iv]            Bussel J, Cheng G, Saleh M et al.  Eltrombopag, an Oral Platelet Growth Factor, for the Treatment of Patients with Chronic Idiopathic Thrombocytopenic Purpura. N Engl J Med 2007;357(22):2237-2247

[v]     Bussel J, Proven 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: 641–48

[vi]    Osterborg A, Kipps T, Mayer J et al. Abstract 0494: Single-Agent Ofatumumab, a Novel Cd20 Monoclonal Antibody, Results in High Response Rates in Patients with Fludarabine-Refractory Chronic Lymphocytic Leukemia (CLL) also Refractory to Alemtuzumab or with Bulky Lymphadenopathy. Presented at the 14th EHA meeting, 2009. Abstract# 0494

[vii]    Parkin DM, Bray F, et al.  Global Cancer Statistics, 2002.  CA Cancer J Clin 2005; 55:74-108

[viii]   Kalil N, Cheson BD. Chronic Lymphocytic Leukemia. The Oncologist 1999;4:352-369

[ix]    Rozman C, Montserrat E. Chronic Lymphocytic Leukemia. N Engl J Med 1995;333:1052-1057

[x]      Redaelli A, Laskin BL, Stephens JM et al. The clinical and epidemiological burden of chronic lymphocytic leukaemia. Eur J Cancer Care 2004;13: 279-287

[xi]     Robak T. Novel Monoclonal Antibodies for the Treatment of Chronic Lymphocytic Leukemia. Curr Cancer Drug Targets 2008;8:156-171

[xii]     Erickson-Miller CL, Delrome E, Tian S et al. Preclinical Activity of Eltrombopag (SB-497115), an Oral, Nonpeptide Thrombopoietin  Receptor Agonist. Stem Cells 2009;27:424-430.

[xiii]   Vadhan-Raj S, Verschraegen CF,  Bueso-Ramos C et al.  Recombinant Human Thrombopoietin Attenuates Carboplatin-Induced Severe Thrombocytopenia and the Need for Platelet Transfusions in Patients with Gynecologic Cancer. Ann Intern Med 2000 132: 364-368

[xiv]  Sungaran R, Markovic B, Chong BH. Localization and regulation of thrombopoietin mRNa expression in human kidney, liver, bone marrow, and spleen using in situ hybridization. Blood 1997;89(1):101-7

[xv]   Eltrombopag (Promacta): Thrombopoietin (TPO) receptor agonist approved for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP). Jan 1, 2009 Formulary. Accessed 19 May 2009

[xvi]  Hagenbeek A, Gadeberg O, Johnson P et al. First clinical use of ofatumumab, a novel fully human anti-CD20    monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase I/II trial. Blood 2008;111:5486- 5495      

[xvii]   Cancer Research UK: About monoclonal antibodies. Accessed 19 May

[xviii]   Teeling JL, Mackus WJM, Wiegmann LJJM et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20. J Immunol 2006;177:362-371