Application Data Show PROMACTA Significantly Raised Platelet Counts and Lowered Bleeding Risk in Clinical Trials for the Short-Term Treatment of Patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP)
PHILADELPHIA and LONDON, Dec. 20 /PRNewswire-FirstCall/ -- GlaxoSmithKline (NYSE: GSK; London) today announced the submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for approval to market PROMACTA(TM) (eltrombopag). If approved, eltrombopag would be the first oral platelet growth factor therapy for the short-term treatment of previously treated patients with chronic idiopathic thrombocytopenic purpura (ITP) to increase platelet counts and reduce or prevent bleeding. Chronic ITP is a disorder marked by increased platelet destruction and/or inadequate platelet production in the blood, which causes an increased risk of bruising and bleeding.(1,2) Eltrombopag is an investigational, once-daily oral treatment that induces the proliferation and differentiation of cells in the bone marrow to produce platelets.
"Patients with chronic ITP do not have a treatment option that offers the convenience of an oral platelet growth factor," said Paolo Paoletti, M.D., Senior Vice President of the Oncology Medicine Development Center at GSK. "GSK is pleased with the data provided to support the NDA and hopeful that, if approved, PROMACTA may provide physicians and chronic ITP patients with a new, convenient and effective option for treating this difficult disease."
GSK also plans to submit a Marketing Authorization Application (MAA) for eltrombopag in Europe in 2008.
About the Data Submitted
The NDA submission is supported by the largest database of clinical trial information on investigational therapies for chronic ITP patients. Two pivotal trials, one Phase III trial and one Phase II trial, were submitted to support the NDA submission.
About the Phase III Data(3)
The Phase III study was an international, randomized, double-blind, placebo-controlled trial that enrolled 114 adults with chronic ITP and baseline platelet counts of less than 30,000/microliter. The primary endpoint in this study was a platelet count of greater than or equal to 50,000/microliter after up to six weeks of therapy. An endpoint of 50,000/microliter was selected because at a platelet count of greater than 50,000/microliter patients have a low risk of bleeding and bruising. Eligible patients must have had a platelet count less than 30,000/microliter, had failed or stopped responding to one or more chronic ITP therapies such as corticosteroids, immunoglobulins and/or splenectomy. Patients were allowed to continue on a concomitant chronic ITP medication, provided their dose had been stable for at least a month prior to enrollment. These patients were randomized to either placebo or eltrombopag 50mg (76 patients) once daily for up to six weeks. Patients were assessed for platelet count weekly and for six weeks following discontinuation of treatment with eltrombopag. Bleeding events were assessed weekly using the World Health Organization (WHO) bleeding scale. The study was originally presented by investigator Drew Provan, M.D., Senior Lecturer in Haematology, Department of Haematology, Royal London Hospital, U.K. at the 2007 Congress of the European Hematology Association in Vienna, Austria.
At the end of the trial, 59% of eltrombopag treated patients on the 50mg dose and 16% of placebo treated patients achieved a platelet count of greater than or equal to 50,000/microliter. Importantly, there was a significantly lower incidence of bleeding during treatment with eltrombopag compared to placebo (p=0.029). Clinically significant serious bleeding was 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 common AEs occurring in at least 5% of eltrombopag subjects included nausea, nasopharyngitis, diarrhea and vomiting.
About the Phase II Data(4)
The Phase II study was a multicenter, randomized, double-blind, placebo-controlled trial examining once daily oral dosing of eltrombopag. One hundred and eighteen adults with chronic ITP and platelet counts less than 30,000/microliter who had relapsed or were refractory to at least one ITP treatment were randomized to eltrombopag (30mg, 50mg, or 75 mg), or placebo. The primary endpoint was the proportion of patients with a platelet count greater than or equal to 50,000/microliter after up to six weeks of dosing.
After six weeks of treatment in chronic ITP patients, eltrombopag at daily doses of 30mg, 50mg and 75mg elevated platelet counts to greater than or equal to 50,000/microliter in 28% (8/29), 70% (19/27) and 81% (21/26) of patients respectively compared to 11% (3/27) of patients receiving placebo (pless than0.001). After seven days of treatment 44% and 62% of patients receiving eltrombopag 50mg and 75mg, respectively, achieved a platelet count of greater than or equal to 50,000/microliter. After 15 days, 88% and 81% of patients receiving eltrombopag 50mg and 75mg respectively had responded, with the median platelet counts approaching the normal range (i.e., 150-400,000/microliter). Platelet counts rose to greater than 200,000/microliter in 4% (1/27) of placebo-treated patients and in 14% (4/29), 37% (10/27) and 50% (13/26) of eltrombopag 30mg, 50mg and 75mg-treated patients respectively.
Eltrombopag was generally well tolerated in this study. The most common AE, mild-to-moderate headache, was observed at similar rates in both the eltrombopag 30mg (13%), 50mg (10%), 75mg (21%) and placebo (21%) arms. At least one AE was reported in 47%, 47% and 61% of patients in the eltrombopag 30mg, 50mg and 75mg groups respectively, compared with 59% in the placebo arm.
Phase II study results were published in the November 29, 2007 issue of New England Journal of Medicine.
About Idiopathic Thrombocytopenic Purpura There are estimated to be between 50,000-100,000 individuals diagnosed with chronic ITP in the U.S.(5) People with chronic ITP often bleed from small blood vessels causing bruises, nosebleeds or even fatal gastrointestinal or intra cerebral bleeds.(1)
About PROMACTA (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. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals (Nasdaq: LGND). 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 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 www.gsk.com.
Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the 'Business Review' in the company's Annual Report on Form 20-F for 2006.
Note to Editors
PROMACTA(TM) is the proposed registered trademark of the GlaxoSmithKline group of companies to be used in the United States.
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References:
(1) National Heart, Lung, and Blood Institute. Diseases and Conditions Index. http://www.nhlbi.nih.gov/health/dci/Diseases/Itp/ITP_WhatIs.html. Accessed November 12, 2007.
(2) Cines DB, Blanchette V. Idiopathic thrombocytopenic purpura. N Engl J Med. 2002;364: 995-1008.
(3) Data on File, GlaxoSmithKline.
(4) 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.
(5) Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic purpura. Annu Rev Med. 2005;56:425-442.
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