As MabThera (rituximab) reaches ten years of market availability in Europe for the treatment of non-Hodgkin's lymphoma (NHL), what does the future hold for the monoclonal antibody (MAb)?
Approved in June 1998 by the EC, although launched earlier in the US (where it is known as Rituxan), rituximab (formerly IDEC-C2B8) was the first anticancer MAb, heralding an influx of the molecules into treatment regimens for multiple tumour types. Originally discovered by IDEC (now Biogen Idec) and jointly developed along with Genentech, Roche and Zenyaku Kogyo, the MAb targets the CD20 protein that is expressed on over 95 per cent of B-cell lymphomas. It was the first MAb therapy to demonstrate a clinically-significant antitumour response, which finally provided proof of principle that these molecules could be efficacious, as well as specific and less toxic. Such a combination of attributes has seen rituximab realise significant revenue, with sales of US$2,252 million in 2006 and US$2,515 million in 2007.
Rituximab was initially approved to treat only a specific subset of patients with NHL. Over the years, the MAb has gained approval to treat additional types of NHL and has become a front-line therapy when used in combination with various chemotherapy regimens. But what about the future of the MAb? Ongoing clinical studies are investigating the long-term use of rituximab as a maintenance therapy to prevent relapse in patients with follicular lymphoma. These trials have shown that maintenance therapy prolongs the duration of remission and that the MAb can be safely administered for up to two years. Additionally, rituximab is in Phase III trials for relapsed and first-line chronic lymphocytic leukaemia. Rituximab has also been approved in areas outside of oncology, such as for the treatment of rheumatoid arthritis, and is being investigated as a therapy for lupus, multiple sclerosis and platelet disorders.
Sales of rituximab look set to remain at a steady level for the next five years, however, in April 2007, Dr Reddy's Laboratories launched Reditux, its brand of rituximab, in India. Reditux, for the treatment of NHL, is priced at around half the originator’s price. Dr Reddy's also announced plans to market Reditux in other markets, including the US, when the product's patent expires in 2015.
The success of rituximab has paved the way for the development and approval of additional anticancer MAbs, treating tumour types such as colorectal, breast, lung, and head and neck cancer. Rituximab has not only altered the way that NHL is treated, but it has significantly changed the approach to cancer drug development. MAb therapies are now an essential part of cancer treatment regimens and clinical trials. Future challenges will involve how to best incorporate new MAb therapies with current treatments, including new forms of immunotherapy. Despite the threat of future biosimilar competition, there is clearly life still left in the original MAb.
Matthew Dennis - Editor, Cancer Drug News