A clinical trial run by consultant opthalmologists and statisticians in the UK has added fuel to the fire over the respective costs and use of Lucentis (ranibizumab) and Avastin (bevacizumab) to treat wet age-related macular degeneration (AMD).

The publication of the study results in the BMJ closely follows the news that ministers in the UK have asked the National Institute for Health and Clinical Excellence to look at the possibility of assessing the clinical and cost effectiveness of the much cheaper Avastin (Roche/Genentech) as an alternative to treatment with Lucentis (Novartis/Genentech) for wet AMD on the National Health Service.

This is despite Avastin not being licensed for wet AMD indication in the UK. The proposal mirrored the controversy of the relative price and value of Lucentis and Avastin for that indication in other markets such as the US. Globally, there is substantial off-label use of bevacizumab for wet AMD, despite Genentech’s efforts to discourage this strategy.

In the prospective randomised controlled study (the ABC Trial) at three ophthalmology centres in the UK, 131 patients with wet age-related AMD were randomised to either bevacizumab injections at six-week intervals or to the standard of care available when the trial started in 2006. The study did not include, or make any direct comparison with, ranibizumab for wet AMD.

The primary outcome measure was the proportion of patients gaining 15 or more letters of visual acuity in sight tests after 54 weeks. Secondary outcomes were the proportion of patients with stable vision and mean change in visual acuity.

Of the 131 patients enrolled, five did not complete the study due to adverse events, loss to follow-up or death (the average age of the participants was 81 years). Among those patients remaining, 21 or 32% of the bevacizumab group gained 15 or more letters from baseline visual acuity over the 54-week period, compared with 3% in the standard care group.

The proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly higher in the bevacizumab group (91%) than in patients on the standard of care (67%).

Average visual acuity improved by seven letters in the bevacizumab patients with a median of seven injections, against a decrease of 9.7 letters in the standard care group. The initial improvement in the bevacizumab group at week 18 was sustained through to week 54. Bevacizumab treatment was also associated with a low level of serious ocular adverse effects.

“The much lower cost and longer duration of action of bevacizumab compared with the only other intervention (ranibizumab) that results in visual recovery for the average patient with neovascular AMD, and its superiority to other licensed treatments as shown in this study, support its immediate implementation in healthcare systems whose budgetary limitations prevent patients’ access to ranibizumab,” commented the authors led by Adrian Tufall, from Moorfields Eye Hospital in London. “This would have a rapid impact of reducing incident global blindness.”

In an accompanying editorial for the BMJ, however, Usha Chakravarthy, professor of ophthalmology and vision sciences at Royal Victoria Hospital, Belfast, stressed that, while the ABC Trial “fills a gap in the evidence base and showed robustly that bevacizumab is better than no treatment, photodynamic therapy or six-week intravitreal pegaptanib sodium, it does not tell us whether the drug is as effective as ranibizumab”.

Early results from a small, single-centre randomised controlled trial comparing bevacizumab and ranibizumab, published last year in the American Journal of Ophthalmology, found no difference in efficacy between the two drugs, Chakravarthy pointed out. She also noted that the potential for systemic adverse events remains a concern in patients receiving intraocular therapy aimed at inhibiting vascular endothelial growth factor.

While the absence of serious adverse arterial thromboembolic events in the ABC Trial is “reassuring”, off-label use of bevacizumab should not be encouraged until the large randomised trials currently comparing the drug with ranibizumab for AMD report their findings, Chakravarthy concluded.