GlaxoSmithKline announced 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.
"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 US to provide the data to bring this product to market in Europe."
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.
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 US and published in Blood and The Journal of Clinical Oncology respectively.
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. 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. 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.
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, and 39 of those patients had relapsed following, or were refractory to, two or more prior chemotherapy treatments. 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.
Nelarabine received EMEA orphan drug status in June 2005. In the US, where it is marketed as Arranon, nelarabine received Orphan Drug status in December 2003 and FDA approval in October 2005.
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, recommending the product for approval.