GlaxoSmithKline receives approval for Atriance in Europe for difficult-to-treat leukaemias and lymphomas

London, UK - 28 August 2007 - GlaxoSmithKline announced today that Atriance® (nelarabine solution for infusion) has received approval from the European Commission for the treatment of patients with T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to, or has relapsed following, treatment with at least two chemotherapy regimens.[1]

"The approval of nelarabine for this orphan indication, addresses the real patient need that exists in these rare types of leukaemia and lymphoma", said Andrew Witty, President, European Pharmaceuticals, GlaxoSmithKline. "Full development for nelarabine began in the 1990's and it has taken over a decade of GSK development and participation in innovative collaborations with well recognised organisations such as the National Cancer Institute (NCI) in the U.S. to provide the data to bring this product to market in Europe."

There are only a few hundred patients diagnosed with relapsed/refractory T-ALL/T-LBL each year in Europe and patients with T-ALL and T-LBL tend to have a worse prognosis than patients with B-cell disease.

"This is a significant and important approval for those patients affected and their specialist physicians across Europe. Nelarabine may offer a valuable chance for patients with few existing treatment options to go on to have potentially curative treatment, such as a stem cell transplant", said Professor Dieter Hoelzer, from J.W.Goethe Universität, Germany. "Many therapies currently used are combinations of cytotoxic drugs which can have a high rate of toxicity. Nelarabine given as a single drug has shown activity and a predictable side-effect profile, and the way it is administered means some patients are able to return home between cycles."

The approved indication for nelarabine is based on data from two, multi-centre pivotal Phase II clinical trials, both of which were conducted in collaboration with the NCI in the U.S.and published in Blood[2] and The Journal of Clinical Oncology[3] respectively.

Adult patients
A Phase II study of adult patients with relapsed or refractory T-ALL or T-LBL was conducted to assess the efficacy and safety of nelarabine.40 patients with relapsed or refractory T-ALL and T-LBL were enrolled, with 39 patients having received at least one dose of nelarabine. A subset of 28 patients out of 39, had relapsed following, or were refractory to, two or more prior chemotherapy treatments.2 Six patients out of the subset of 28 patients (21%), had a complete response* with or without restoration of normal blood cell levels and one patient from this group went on to receive a stem cell transplant.5 Also, the German ALL Study Group published their experience in 53 adult patients with refractory relapse of T-ALL. 47% achieved a remission and 74% of the complete response patients were transferred to a stem cell transplant.[4]

Paediatric patients
A Phase II study evaluated 153 paediatric patients (<21 years old) with relapsed or refractory T-ALL or T-LBL to assess the efficacy and safety of nelarabine. A subset of 84 patients were treated at the recommended dose and schedule of administration,3 and 39 of those patients had relapsed following, or were refractory to, two or more prior chemotherapy treatments.[5] 23% of these 39 patients experienced a complete response* with or without restoration of normal blood cell levels, and four of these patients went on to receive a stem cell transplant.5

*Complete response is the disappearance of all detectable signs of disease; this does not mean the cancer has been permanently cured.

The most common adverse effects during therapy with nelarabine included haematologic (blood) toxicity, fatigue, and nausea.2,3 In addition, severe neurological events have been reported with the use of nelarabine(see prescribing information for full information).

Nelarabine received EMEA orphan drug status in June 2005.[6] In the US, where it is marketed as Arranon®, nelarabine received Orphan Drug status in December 2003 and FDA approval in October 2005.[7],[8]

The European Commission approval of nelarabine results in a single marketing authorisation with unified labeling that is immediately valid in all 27 EU Member States with identical national licences usually issued in Norway, Iceland and Liechtenstein. The Commission’s decision follows a Positive Opinion by the European Medicines Agency (EMEA) in June 2007[9], recommending the product for approval.

About nelarabine
Nelarabine is a nucleoside analogue prodrug that when administered intravenously is converted to ara-G and then to its active form, ara-GTP.3 Accumulation of ara-GTP in T-cells leads to inhibition of DNA synthesis, which results in programmed cell death.[10]

About Acute Lymphoblastic Leukaemia (ALL) and Lymphoblastic Lymphoma (LBL)
ALL is a cancer of the white blood cells, the cells in the body that normally fight infections. It is a rare, difficult to treat disease that is more common in children and progresses rapidly in the absence of effective therapy. ALL is the most common cancer in children, representing 23% of cancer diagnoses among children younger than 15 years of age.[11] T-ALL represents a minority of the ALL population and has a particularly poor prognosis after relapse.

LBL is a type of non-Hodgkin's lymphoma (NHL), a cancer of the lymphatic system, which occurs more often in children than adults. T-LBL patients represent a subset of this population.

GSK in Oncology
Nelarabine further demonstrates GSK’s move into thehaematology/oncology arena and showcases GSK’s dedication to producing innovations in cancer that will make 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 partnerships 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.

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.

Notes to editors:
· Atriance® and Arranon® are registered trade marks of the GlaxoSmithKline group of companies.
· Atriance® is the trade mark used by GlaxoSmithKline for nelarabine in Europe.
· Arranon® is the trade mark used by GlaxoSmithKline for nelarabine in the United States.

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

References:
[1] http://www.emea.europa.eu/htms/human/epar/eparintro.htmAugust 2007
[2] DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine Induces Complete Remissions in Adults with Relapsed or Refractory T-lineage Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma: Cancer and Leukemia Group B Study 19801: Blood 2007;109:1810-1816
[3] Berg SL, Blaney S, Devidas M, et al. Phase II Study of Nelarabine (compound 506U78) in children and young adults with refractory: A report from the Children’s Oncology Group. Journal of Clinical Oncology 2005; 23(15), (May 20):3376-3382
[4] Gökbuget N, Arnold R, Atta J et al. Compund GW506U78 had high single-drug activity and good feasibility in heavily pretreated relapsed T-lymphoblastic leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LBL) and offers the option for cure with stem cell transplantation [abstract]. Blood 2005; 106:#150
[5] Cohen MH, Johnson JR Massie T, et al. Approval Summary: Nelarabine for the Treatment of T-Cell Lymphoblastic Leukemia/Lymphoma. Clin Cancer REs 2006;12(18), (Sept 15):5329-5335
[6] EMEA. Atriance Orphan Drug Status. June 2005. GSK data on file
[7] Arranon Fast Track designation. Orphan Drug Status. December 2003. GSK data on file
[8] Food Drug Administration. http://www.fda.gov/bbs/topics/NEWS/2005/NEW01251.html. Last accessed May 3 2007
[9] http://www.emea.europa.eu/pdfs/human/opinion/26744307en.pdf June 2007
[10]Rodriguez C, Gandhi V. Arabinosylguanine-induced Apoptosis of T-Lymphoblastic Cells. Cancer Research. October 1, 1999; 59: 4937-4943
[11]National Cancer Institute Fact Sheet, last updated 9/15/2005 www.nci.nih.gov/cancertopics/pdq/treatment/childall/healthprofessional

Enquiries:
UK Media enquiries: Philip Thomson (020) 8047 5502; Alice Hunt (020) 8047 5502; Joss Mathieson (020) 8047 5502; Claire Brough (020) 8047 5502
European Analyst/Investor enquiries: David Mawdsley (020) 8047 5564; Sally Ferguson (020) 8047 5543

SOURCE: GlaxoSmithKline

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