GlaxoSmithKline announced today that Atriance® (nelarabine solution for infusion) has received a positive opinion from the European Medicines Agency (EMEA) for the treatment of T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) patients whose disease has not responded to, or has relapsed following, treatment with at least two chemotherapy regimens.[1] Nelarabine will now be considered for final marketing approval by the European Commission."Nelarabine may offer some patients the chance to go on to have potentially curative treatment, such as a stem cell transplant, so we are delighted that nelarabine has been granted a positive opinion from the EMEA,” said Paolo Paoletti, SVP and Global Head of Oncology Research and Development, GSK. “We are immensely proud of our involvement in the development of this orphan drug for such a rare disease, and believe it is an excellent example of our long-term commitment to improving the lives of patients through our ongoing investment in R&D - be they in their tens of thousands or, as in this case, as few as hundreds.”
T-ALL and T-LBL are rare, difficult to treat forms of acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL). There are only a few hundred cases of relapsed T-ALL each year in Europe.[2] Patients with T-ALL and T-LBL tend to have a worse prognosis than patients with B-cell disease. Given that there are few treatment options for those who do not respond to, or have relapsed following, at least two chemotherapy regimens, nelarabine is an important advance for this group of patients.
Nelarabine received EMEA orphan drug status in June 2005.[3] In the US, where nelarabine is marketed as Arranon® it received orphan drug status in December 2003 and FDA approval in October 2005.[4],[5]
The data submitted
The EMEA reviewed data from two, multi-centre pivotal Phase II clinical trials, both of which were conducted in collaboration with the National Cancer Institute (NCI) and published in Blood[6] and The Journal of Clinical Oncology.[7]
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.6 Six 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.8 A median overall survival of 20 weeks was reported.6
Paediatric patients
A Phase II study evaluated 153 paediatric patients (<21 years old) with relapsed or refractory T-ALL or T-LBL to access the efficacy and safety of nelarabine. A subset of 84 patients were treated at 650mg/m2 dose for 5 days,7 and 39 of those patients had relapsed following, or were refractory to, two or more prior chemotherapy treatments.[8] 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.8
The most common adverse effects during therapy with Atriance included haematologic (blood) toxicity, fatigue, and nausea.6,7 In addition, severe neurological events have been reported with the use of nelarabine.
Registration dossiers for nelarabine have been filed in Canada, Japan, Switzerlandand Israel.
About nelarabine
When administered intravenously nelarabine is converted to ara-G and then its active form, ara-GTP.7 Accumulation of ara-GTP in cells leads to inhibition of DNA synthesis, which results in programmed cell death.[9]
About Acute Lymphoblastic Leukemia (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 percent of cancer diagnoses among children younger than 15 years of age.[10] 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 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 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.
References
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[1] European Medicines Agency. Summary of Opinion. Atriance (nelarabine). June 2007
[2] Decision Resource, Onkos Study #2, Acute Lymphoblastic Leukemia, November 2006
[3] EMEA. Nelarabine Orphan Drug Status. June 2005. GSK data on file
[4] Arranon Fast Track designation. Orphan Drug Status. December 2003. GSK data on file
[5] Food Drug Administration. http://www.fda.gov/bbs/topics/NEWS/2005/NEW01251.html. Last accessed May 3 2007
[6] 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 Mar 7; [Epub ahead of print]
[7] 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
[8] 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
[9]Rodriguez C, Gandhi V. Arabinosylguanine-induced Apoptosis of T-Lymphoblastic Cells. Cancer Research. October 1, 1999; 59: 4937-4943
[10] National Cancer Institute Fact Sheet, last updated 9/15/2005 www.nci.nih.gov/cancertopics/pdq/treatment/childall/healthprofessional
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