In a landmark move, the UK is to launch its own head-to-head study of Genentech and Novartis’ blindness drug Lucentis (ranibizumab) versus the US biotechnology giant’s Avastin (bevacizumab) after it emerged that ophthalmologists and primary care trusts are shunning the approved medicine in favour of the much cheaper cancer therapy Avastin, which is frequently used off-label to treat the wet form of age-related macular degeneration.

The move was brought to the fore in a report in The Guardian yesterday, although it has been known for some time that Avastin is being favoured over Lucentis on cost-grounds. But now it seems that the National Health Service is prepared to try and settle the argument once and for all as it faces trying to pay for a plethora of expensive new treatments whilst its primary care trusts struggle with huge deficits and public backlash.

Novartis’ Lucentis and Pfizer’s Macugen were cleared for marketing in Europe in 2006, but in the UK were faced with a 13-month delay waiting for the National Institute for Health and Clinical Excellence to make its decision on cost-effectiveness. When the draft recommendation came, just last month, it was met with derision: Macugen was blocked outright, while Lucentis received a thumbs up for people with predominantly classic subfoveal choroidal neovascularisation wet AMD, but only when both eyes are affected and then only in the better seeing eye. In stark contrast, Scotland has given its blessing to the use of both Macugen and Lucentis on its National Health Service.

Alongside this, there is a huge cost differential between Lucentis and Avastin that means many practitioners and PCTs choose to use Genentech’s cancer drug off-label over Lucentis. The AMD-approved Lucentis is £761.20 per injection, while Avastin can divided into much smaller doses that cost as little as £10 per shot, says The Guardian. And this is one of the reasons Genentech has given for not pursuing the AMD indication for Avastin, citing problems over sterility during the splitting of the product. Additionally, it points to Avastin’s longer half-life (the time the compound remains in the body), which it says could have potentially adverse effects on the retina, as well as the different manufacturing standards required for ophthalmic compared to cancer therapies. The US major has previously said it will not consider seeking regulatory approval of Avastin in AMD, because it would essentially have to go back to the drawing board and conduct preclinical trials to determine the drug’s toxicity in this indication, when it already has an approved medicine for this use in the shape of Lucentis.

About 26,000 new patients present themselves with AMD each year. In 2004, the RNIB published an estimate of the costs of blindness. It showed that the annual total cost of sight loss was in the region of £4.9 billion.

Debate hits Parliament

And the debate has made it to Parliament. Earlier this year, before NICE’s initial recommendation, the then Secretary of State for Health, Patricia Hewitt, claimed that: “No patient should be refused Lucentis or Macugen simply because NICE guidance does not yet exist.” She added: “If a clinician wants to use Avastin and the patient is willing to have an unlicensed drug used, it is available on the clinician's judgment, which will continue to be the case within the NHS.”

But a subsequent House of Commons interchange in April saw Sir George Young, Conservative state: “The Department of Health has said that the NICE review process should not be a barrier to the use of new treatments, but it has in effect opted out and delegated the decision on whether funding should be authorised to the 152 primary care trusts in England. Many are overspent, and do not have the resources to conduct the effective reviews of the treatment that they are obliged to carry out.”

Talking specifically about Lucentis and Avastin, he continued: “Other PCTs have mitigated the cost by authorising the use of the unlicensed treatment Avastin, which is having good results. The Secretary of State has suggested a head-to-head trial between Avastin and Lucentis. I understand that Professor Usha Chakravarthy in Belfast and Professor Simon Harding in Liverpool are leading such a trial with funding from the Health Development Agency. If it goes ahead, the trial will provide good evidence that would allow regulators such as NICE to recommend the use of Avastin over Lucentis and save the NHS a considerable amount of money.”

Indeed he quoted consultant ophthalmic surgeon Michael Lavin from Manchester Royal eye hospital as saying: “If all patients with wet AMD in the UK were treated with standard dose Lucentis, costs to the NHS by year two would be approximately £1,008m a year; if Avastin were used the cost would be about £4 million a year.”

And Andy Burnham, Minister of State at the Department of Health, confirmed in response that the National Institute for Health Research health technology assessment programme has agreed to fund a head-to-head trial of Avastin and Lucentis over a 42-month period. The project was expected to start on 1 May.

But Novartis Ophthalmics in the UK refuted both Young's and Lavin's comments, telling PharmaTimes World News that: "The fact is that this head-to-head study will not lead to a license in wet AMD for Avastin nor will it lead to approval by NICE as NICE do not assess medicines in respect of their usage for unlicensed indications." As regards the cost of Lucentis, the company added: "Data submitted to the NICE's ongoing review of these treatments estimates the cost of Lucentis to be £27 million in year one rising to £69 million in year three - these figures are far from the mentioned £1,008 million a year. Now that Lucentis has been licensed, the correct dose and price have been used in the cost modelling submitted to NICE. Novartis have shared this information widely, including others working on developing cost estimates for treating wet AMD. It is hoped that from this point onwards all healthcare professionals will use these up to

date and accurate cost assessments."

Meanwhile, in a submission to NICE ahead of its health technology appraisal, the Royal College of Ophthalmologists included details from a survey of its members showing that the vast majority believed the use of Avastin off-label in AMD would be justified ahead of NICE guidance on Lucentis, though they were hung (11 vs 11) on whether this should be the case after publication of the final appraisal.

This report includes comments taken from the uncorrected transcript of the Committee’s oral evidence sessions, which neither the witnesses nor the Members have had the opportunity to correct.