Date Posted: 02 June 2010
Commentary from the UK's Royal College of Ophthalmologists (RCO) has advised against the off-label use of Avastin (bevacizumab) for the treatment of wet age-related macular degeneration.
Controversy surrounding the off-label use of Avastin for wet AMD has been covered widely in both the specialist and general press. The drug, developed by Genentech/Roche, is a full recombinant humanized monoclonal antibody with a molecular weight of 149kDa and is licensed for the treatment of metastatic colorectal and breast cancer. Avastin binds all isoforms of vascular endothelial growth factor-A (VEGF-A), a factor known to be critical in the pathogenesis of choroidal neovascularisation in AMD. A very similar drug, Lucentis (ranibizumab), is also a humanized therapeutic monoclonal antibody fragment that binds all isoforms of VEGF-A but has a molecular weight of 48kDa. In addition to being three times smaller than Avastin, Lucentis also differs by 6 amino acids in the Fab domain and has a shorter serum and vitreous half-life than that of the larger Avastin. Both drugs were developed and marketed by the same company.
The RCO's current position on injection therapy for age-related macular degeneration is available on their website (www.rcophth.ac.uk). However, much of the controversy has focused on the very large price differential between Avastin and Lucentis - Avastin costs £230 for a 100mg vial while Lucentis costs £761 for 0.23ml. Under an arrangement with Novartis the UK NHS pays for the first 14 treatments of Lucentis at a cost of £149,800 per patient amounting to approximately £300M per annum for the Exchequer. Even with such coverage many patients are unable to afford the approved drug and so pressure for off-label use of Avastin has been significant. Head to head trials comparing the two drugs in AMD treatment are due to report in late 2011 and early 2012.
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