The much cheaper but unlicensed option is as effective, according to interim results, but safety remains a talking point
Interim results from a much anticipated comparative study of two drugs support what many ophthalmologists already believe: that ranibizumab and bevacizumab are equally good for the treatment of neovascular age related macular degeneration (AMD), a leading cause of blindness in developed countries.
The two drugs were developed by, Genentech, part of Swiss drugmaker Roche, and are structurally similar - ranibizumab is a fragment of bevacizumab - which suggests similar biological activity.
While ranibizumab is approved for the treatment of neovascular AMD, bevacizumab, marketed as anticancer drug Avastin, is not. But bevacizumab is widely used by ophthalmologists because it is much cheaper.
The Catt (Comparison of AMD Treatments Trials) research group looked at 1200 patients with neovascular AMD. After one year, they found that the two drugs improved vision to the same extent when given according to the same, pre-determined schedule. The performance of bevacizumab changed when given ’as needed’ whereas the performance of ranibizumab stayed the same. Nevertheless, the researchers concluded: ’In each of the head-to-head comparisons of ranibizumab with bevacizumab, the drugs had equivalent effects on visual acuity at all time points throughout the first year of follow-up.’
In a New England Journal of Medicine editorial, Philip Rosenfeld, an ophthalmology professor at the University of Miami, US, said: ’Health care providers and payers worldwide will now have to justify the cost of using ranibizumab. Regulators in certain countries will be forced to reconsider their policies that make it illegal to use drugs off-label, particularly when so many of their citizens cannot afford ranibizumab.’
Novartis, which markets ranibizumab outside the US (as Lucentis), highlighted an industry funded study that looked primarily at safety, data from which was presented at a meeting of the Association for Research in Vision and Ophthalmology. The researchers analysed claims made through US health insurance programme Medicare and concluded that patients taking bevacizumab may be at higher risk of stroke and death than patients taking ranibizumab. However, the researchers say that the study was ’limited by incomplete information’, including lipid levels, blood pressure levels and behaviour, with respect to smoking.
Meanwhile, patient advice seems unchanged. The UK Royal College of Ophthalmologists urged caution in interpreting the results of the trial, adding that ’ranibizumab remains the recommended treatment for wet [neovascular] AMD’.
The Macular Disease Society, a UK charity, said ’there is insufficient data from this trial to draw firm conclusions about whether Avastin is as safe as Lucentis. As a result, our general position remains that patients with wet age-related macular degeneration should be treated with the licensed and approved drug for the condition, which is Lucentis’.
The unusual situation raises a question: Could an unrelated third party put ranibizumab forward for licensing authorisation for the treatment of neovascular AMD? Healthcare providers might be motivated to try.
A spokesperson for the UK Medicines and Healthcare Products Regulatory Agency told Chemistry World that any individual or group can submit an application for any drug candidate. But the applicant would need to provide comprehensive data on quality, safety and efficacy.
The CATT research group, N Engl J Med, 2011, DOI: 10.1056/NEJMoa1102673