Avastin is as effective as Lucentis for wet AMD and could save NHS £84m a year, study shows

New trial results have confirmed that bevacizumab (Avastin) and ranibizumab (Lucentis) perform very similarly in the treatment of wet age related macular degeneration.

Using bevacizumab, which is much cheaper but is unlicensed for the condition, could save the NHS £84m a year, say the British researchers responsible for one of the trials.

The new data come from the second year of the comparison of age related macular degeneration treatment trials (CATT) and the interim analysis of one year’s results from the inhibit VEGF in age related choroidal neovascularisation (IVAN) trial. Both were presented at the annual meeting of the Association for Research in Vision and Ophthalmology at Fort Lauderdale in Florida and published in Ophthalmology.1 2

The trials were designed to discover whether patients given ranibizumab could read five more letters (CATT) or 3.5 more letters (IVAN) on an opticians’ chart, or better, than patients given bevacizumab. In neither trial was this limit exceeded, showing that bevacizumab was not inferior to ranibizumab by these margins.

There was a small but statistically insignificant difference of less than two letters in favour of ranibizumab. The CATT triallists concluded: “Ranibizumab and bevacizumab had similar effects on visual acuity over a two-year period.” The IVAN triallists say that the comparison of visual acuity was inconclusive but consistent with the drugs having “similar efficacy.”

Neither study was large enough to detect differences in rare side effects, but CATT did show that the proportion of patients with one or more serious adverse events was higher (at 39.9%) among those given bevacizumab for two years than among those given ranibizumab (31.7%). The same trend was seen in the IVAN trial but did not reach statistical significance.

The IVAN triallists unexpectedly found an increase in the risk of heart attack or stroke with ranibizumab, but the numbers were small (six cases against one).

Usha Chakravarty of Queen’s University in Belfast, who led the IVAN trial, said, “Regardless of which drug they received, the average person improved by approximately one line. And when it comes to comparing the two drugs, the difference was extremely small: less than two letters of the eye chart.

“Both drugs were equally safe, and the small differences that were found in terms of heart attack and strokes were cancelled out when we looked at both our study and the American study. In terms of other adverse events which put patients in hospital, these differences were consistent in both studies, and we did observe a slight increase with bevacizumab.”

Both drugs were developed by Genentech, which became part of Roche. Novartis has the licence for ranibizumab outside the United States. Bevacizumab was developed as an anticancer drug that works by inhibiting the growth of blood vessels. Ranibizumab, with a different molecular structure but similar mode of action, was developed for wet macular degeneration and licensed for that indication. Among other differences, it has a much shorter half life after injection, which should lead to a lower adverse event profile. But bevacizumab is priced differently, enabling it to be divided into several doses for ophthalmic use and greatly reducing its cost.

The IVAN trial measured what this difference would mean to the NHS. Used monthly, treatment with ranibizumab cost £9656 a year, whereas bevacizumab cost £1654. When used on an “as needed” basis—that is, only when disease progression was noted, the approach preferred by ophthalmologists—the cost of ranibizumab treatment came down to £6398 a year and that of bevacizumab only to £1509, because the costs of administration and monitoring as a proportion of the total cost are greater for bevacizumab.

If the NHS across the UK was to use the cheaper drug, it would save £84.5m a year, if 17 295 eyes were treated, the team estimates.

Novartis, which markets ranibizumab in the United Kingdom, says that it has a well established safety profile as a result of its clinical trial programme and continuing post-market surveillance. Neither CATT nor IVAN was powered for safety, yet the CATT two year results did show a significantly higher risk of serious adverse events for the unlicensed drug.

Neither CATT nor IVAN was equivalent to the clinical trials needed to obtain a licence, and it was unlikely that bevacizumab would ever be licensed for ophthalmic use, said Christopher Brittain, senior medical adviser to Novartis.

Although the National Institute for Health and Clinical Excellence (NICE) recommended 18 months ago that bevacizumab should be appraised, the Department of Health has not called for an appraisal.

In a statement commenting on the IVAN results, Novartis said that it was in discussions with NICE and the Department of Health “regarding options looking at the cost effectiveness of ranibizumab across all of its indications”—a hint that a compromise on price may be possible.