The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending that marketing authorisations can be granted bendamustine HCI (Levcat, Mundipharma International, Cambridge, UK; also market as Ribomustin and Treanda) in most Member States of the EU. Bendamustine is can now be used a a vital treatment in patients with indolent non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM).[1]
Dr Thomas Mehrling from Mundipharma commented, “We are delighted with this decision and believe it represents a dramatic step towards improved treatment for patients with hematological malignancies.” Following a European Commission decision on this positive opinion and the granting of national licences, the first launches of bendamustine in the European Union are anticipated in mid-2010 in Austria, Denmark, Finland and the UK.
Bendamustine is a highly effective chemotherapy agent which differs from those that are already available due to its unique chemical structure and activity. Bendamustine Hydrocholride (HCI) has shown clinical activity in patients with disease refractory to conventional alkylator chemotherapy. Results from a study by Leoni et al, suggest that bendamustine HCI possesses mechanistic features that differentiate it from other alkylating agents and may contribute to its distinct clinical efficacy profile. [2]
Preclinical data demonstrate that bendamustine HCI acts in two distinct ways to kill cancer cells. Bendamustine HCI damages the DNA in cancer cells, which leads to cell death by a process known as apoptosis (programmed cell death) as well as by an alternate cell death (non-apoptotic) pathway known as mitotic catastrophe (a disruption of normal cell division).
The announcement by the CHMP is particularly important for those patients with common white blood cell malignancies, notably indolent NHL, CLL and MM, including those patients with indolent NHL that have not responded to other therapies, or those patients where their cancer has returned after a period of absence.
Bendamustine is currently licensed in Germany (under the brand name Ribomustin) for CLL, first-line therapy of advanced indolent NHL in a combination protocol, and in combination with prednisone for advanced MM stage II with progress or stage III.[3] Between 2008 and 2009, bendamustine was used to treat 13,357 patients in Germany.[4] In the United States, bendamustine is indicated for the treatment of indolent B-cell NHL that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen and also for the treatment of patients with CLL. [5] Since its launch, 14,000 patients have been treated in the United States.[6]
“New treatments capable of inducing further remission without excessive toxicity are urgently needed. Many of the patients who may benefit from bendamustine currently have no or few treatment options available. This product provides these patients with renewed hope” commented Professor Marco Montillo, Department of Haematology, Niguarda Ca’Granda Hospital, Milan, Italy.
Bendamustine HCI, a white, water soluble microcrystalline powder with amphoteric properties, was first synthesized in 1963 at the Institute for Microbiology and Experimental Therapy in Jena in the former German Democratic Republic (East Germany) by Ozegowski and Krebs. The molecule, originally termed IMET 3393 (4-[5-(bis[2-chloroethyl]amino)-1-methyl-2-benzimidazolyl] butyric acid), was intended to be a ‘bi-functional’ molecule with alkylator and antimetabolite properties [7, 8]
Until 1990 it was only available in the former East Germany. The drug received its first EU marketing approval in Germany where it is marketed under the tradename Ribomustin. SymBio Pharmaceuticals Ltd holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries.
In March 2008, Cephalon Inc received approval from the US FDA to market bendamustine in the US, where it is sold under the tradename Treanda.
References
1. European Medicines Agency website: Accessed March 2010
2. Leoni LM, Bailey B, Reifert J, Bendall HH,et al, Bendamustine (Treanda) Displays a Distinct Pattern of Cytotoxicity and Unique Mechanistic Features Compared with Other Alkylating Agents. Clin Cancer Res 2008; 14(1):309-317
3. Ribomustin SPC
4. IMS Oncology Analyzer- data on file
5. Treanda website: Accessed March 2010
6. Tandem Audit 2010-data on file
7. Forero-Torres A, Saleh MN. Bendamustine in non-Hodgkin lymphoma: the double-agent that came from the Cold War. Clin Lymphoma Myeloma. 2007 Dec;8 Suppl 1:S13-7.
8. Ribomustin EU Safety Data Sheet
