Novartis' Gleevec/Glivec (imatinib), the breakthrough treatment for chronic myeloid leukaemia, may also provide new hope for rheumatoid arthritis sufferers, researchers from Stanford University report in the Journal of Clinical Investigation, adding that the drug blocked the development of the disease in a mouse model.
The results suggest that Gleevec-based therapies could provide “a powerful approach to treat rheumatoid arthritis and other inflammatory diseases,” according to Dr William Robinson, who led the research. The Stanford team investigated the effect of Gleevec on rheumatoid arthritis following reports in 2003 that two RA patients showed an improvement in their symptoms following Gleevec treatment for malignancies from which they were also suffering.
In the latest study with mice, Gleevec - which is also used to treat gastrointestinal stromal tumours - was shown to dampen down key aspects of the animals' immune system, including tumour necrosis factor-alpha release, macrophage and mast cell production, as well as the production of B cells. Crucially, many of these cells are known to build up in the joints of patients with rheumatoid arthritis.
Existing treatments, such as Schering-Plough's Remicade (infliximab) and Wyeth/Amgen's Enbrel (etanercept), which target TNF-alpha, have already shown considerable success in treating patients with severe disease - and reel in billions of dollars apiece. However, not all patients respond to the drugs and experts say new therapies are needed.
The Stanford team says the apparent ability of Gleevec target a large range of immune cells and cytokines implicated in the disease suggests the drug could have an important role to play in the management of rheumatoid arthritis. “Our results provide further rationale for prospective clinical trials to determine whether imatinib provides efficacy in rheumatoid arthritis and other autoimmune diseases,” they say.
The researchers note there is also evidence that a patient receiving Gleevec for cancer showed an improvement in his psoriasis while mast cells - which the study showed are potently inhibited by the Gleevec - are implicated in multiple sclerosis and inflammatory bowel disease.
The news can only be a boon to Novartis: Sales of the drug in the first half of this year were $1.2 billion, a rise of 16% year-on-year. It is Novartis' second biggest selling product. By Michael Day