Payers step up the heat over off-label Avastin (December 1st 2014)

There has been an on-going battle between payers and Novartis/Roche over the off label use of Avastin to treat neovascular age related macular degeneration (AMD). Although Avastin is licensed to treat cancer, it works in the same way as Lucentis which revolutionised the treatment of neovascular AMD. Avastin has been used off label because it is significantly cheaper to use than Lucentis at about a tenth of the cost.

Neovascular AMD is the leading cause of blindness in the elderly in industrialised countries. One estimate suggests that the NHS would save £102 million a year by switching from Lucentis to Avastin. However, both Lucentis and Avastin are owned by Roche and to further complicate matters Lucentis is marketed by Novartis outside of the USA. There is no incentive for Roche to encourage the use of Avastin to treat neovascular AMD when they already have a very effective – and more expensive – drug in Lucentis. Indeed, both Roche and Novartis have every reason to actively discourage the use of Avastin in this way.

The battle in the UK has bubbled under for some years, even after clinical trials found the two drugs to be equally effective in the treatment of neovascular AMD with Novartis raising patient safety concerns. It is now threatening to reach new highs following the recent Cochrane Collaboration review looking at the safety of intravitreal bevacizumab (Avastin) and ranibizumab (Lucentis) which judged them to be equivalent in terms of patient safety.

Following publication of the review, the Royal College of Ophthalmologists called for regulators (MHRA, NICE and the GMC) to remove the obstacles to the use of Avastin for neovascular AMD in the UK. At the same time, the Health Service Journal reported that a number of Clinical Commissioning Groups in England are considering commissioning Avastin for the treatment of neovascular AMD. Previous attempts at such a move by CCGs, or their predecessors PCTs, failed whenNovartis threatened a judicial review of the decision in 2012.

The main barrier for UK doctors over using Avastin off label is that the General Medical Council (GMC) has stated that, although it is perfectly acceptable for doctors to use medicines off label, they should only use them if “there is no suitably licensed medicine that will meet the patient’s need”. In the case of Avastin’s off label use, there is a suitably licensed medicine in Lucentis which could be used.

This is a uniquely European problem and in countries where these barriers do not exist, like the US, Avastin is often the market leading drug for neovascular AMD. However, there are signs that other European countries are increasing the pressure on Naovartis and Roche. The Italian competition authority fined Roche and Novartis  over €180 million because they “colluded to exclude the cheap drug Avastin ... and channel demand towards the much more expensive Lucentis”. The French health regulator the National Agency for Medicines and Health Products Safety (ANSM) has asked Roche  to provide information about the safety and efficiency of Avastin off label to treat neovascular AMD. They will issue their recommendations in 2015.

Of course, it could be argued that the whole situation is irrelevant because the PPRS agreement, which governs drug prices in the UK, requires the industry to reimburse the Department of Health if there is growth in expenditure on branded drugs. On the basis of this, ophthalmologists should be able to use Lucentis to their hearts content and not worry about the cost because any excess will be reimbursed to the DOH.

If only life were that simple! The money does get reimbursed by the industry but it does not go back to the NHS. In fact, no one seems clear about where it goes. The PPRS was hailed as the way to increase the uptake of innovative new products and it should have achieved that. However, the Department of Health managed to undo all the good that it was meant to achieve by not channelling the money gained back into the NHS.

The result of all of this is a mess. On the one hand, it is always better to use a licensed medicine to treat a condition when possible. The licensing system gives reassurance of the effectiveness and safety of the product; and the weight of evidence to support its use is usually far greater than that for an off label use of a medicine. Lucentis is licensed for use in neovascular AMD and Avastin is not. They were both developed by the same company which will not voluntarily seek a licence for Avastin to be used in neovascular AMD.

On the other hand, ophthalmologists would argue that Avastin is safe and effective and they should be able to use the cheaper drug and hence be able to treat a greater number of patients. They can point to good evidence of equivalent effectiveness and patient safety between Lucentis and Avastin. But ophthalmologists are wary of prescribing Avastin off label in case they fall foul of the GMC.

So far this has only been taken up by the specialist media. If the row escalates into legal action or the national media picks up on it, the industry - and the regulators - will not come out of it well. Pharma will look like it is pursuing purely commercial gain at the cost of patients going blind and this will reinforce the poor image of the industry. The regulators will look like they are colluding with the industry to stop doctors from saving the NHS millions of pounds. If there is a lot of media attention, the issue could have wide ranging implications.

There are some complex ethical issues at stake about how we use off label medicines, but the headlines are likely to be about bad pharma and bad regulators. We need an honest debate about the cost of medicines; the prescribing of medicines off label and the value of innovative medicines for the NHS. However, this is unlikely to happen in a battle reflected in newspaper headlines.

David Pruce - Director, PruceConsulting Ltd

Off label prescribing is where a medicine is used to treat a patient whose condition does not fall under the marketing authorisation or license for the medicine. It is fairly common, and quite legitimate, to prescribe off label - particularly in paediatric cases because a lot of medicines have not been tested in children. It can be beneficial to the industry, if a drug is prescribed off label as it extend the use of the drug and even pave the way for new licensed indications. Indeed, there have been a number of cases brought against companies for promoting off-label uses of their drugs.