NHS doctors should be allowed to prescribe a cheaper off-label version of a patented medicine for eye disease wet age related macular degeneration (AMD), says an investigation by The BMJ.
Currently, General Medical Council guidance and European drug licensing laws say that Lucentis (ranibizumab), developed by Novartis and Roche, and Bayer/Regeneron’s Eylea (aflibercept) – that are both approved to treat wet AMD – should be the first choice of treatment for the condition.
Doctors can prescribe drugs off-label – i.e., for conditions they think may be clinically suitable for a medicine but for which it does not have a licence. This is typically reserved for medicines in young children.
But a number of ophthalmologists in the UK and across many mature markets have been prescribing Roche’s cancer drug Avastin (bevacizumab) ahead of Lucentis and Eylea for years, predominately because it is around a tenth of the price of the licensed medicines.
Avastin currently only has cancer licences, but it is chemically similar to Lucentis as they are both anti-VEGF drugs, meaning it can be successfully used for wet AMD. In fact, Roche co-markets Lucentis with Novartis in certain markets as Lucentis is the ‘chemical cousin’ of Avastin.
Over the past three years a number of UK and US government-funded trials have shown that Avastin is as efficacious and safe as Lucentis in treating wet AMD (although there is no direct comparison with Eylea as yet).
Novartis maintains that because of the way Avastin is used for wet AMD, it may increase the risk of infection for some patients, and has actively lobbied against the use of the drug for wet AMD – a position Roche also holds.
The situation came to a head in 2012 when the Swiss firm attempted to sue an NHS Trust in order to get it to stop using Avastin off-label. It eventually dropped the lawsuit after the Trust agreed to use Lucentis instead, but only after Novartis offered a significant price cut.
But using Avastin to treat AMD could release just over £100m back into the NHS, which it could then re-invest into other front-line patient services.
BMJ investigation
Yet new evidence published today by The BMJ reveals a “campaign by the drug manufacturers” to “undermine and divert attention” from the results of these trials, even turning to the charity, Royal National Institute of Blind People (RNIB), for help.
Emails obtained under a freedom of information request show that doctors with ties to Novartis urged some primary care trusts to pull out of one trial. The BMJ said it has also learnt of attempts by Novartis to “derail” a second publicly funded UK trial.
The trial’s chief investigator, Alex Foss, a consultant ophthalmologist at Queen’s Medical Centre, Nottingham told The BMJ how, during the trial’s planning stage, a Novartis representative tried to divert him to Novartis funded work, with the prospect of future funds for personal research projects.
But while the studies have been ongoing, the General Medical Council (GMC) has told doctors it is unlawful to prescribe an “unlicensed” medicine on the grounds of cost.
This change of guidance has left doctors fearful of acting on the trial results.
The BMJ said it has learned that both the ABPI and the MHRA, acting on behalf of the government, lobbied against the proposed new clause. The RNIB has also lobbied the GMC against changing guidance to doctors that would allow more widespread use of off-label drugs.
The Journal’s editor in chief, Dr Fiona Godlee, says new evidence raised by its investigation: “raises questions about the legal and regulatory positions that have skewed clinical practice, fuelled NHS drug costs, and left doctors confused about what they can and can’t prescribe.”
‘Bullying and misinformation’
Dr Godlee says: “Doctors and academics have carried out clinical trials despite threats and intimidation – and doctors leaders should follow suit and not allow themselves to be bullied either. Patients have volunteered to participate in clinical trials thinking that their contribution might save the NHS millions of pounds. It is unethical not to act on their altruism.”
She adds: “Doctors’ leaders also need to sort out the web of misinformation about drug prescribing that has been generated behind closed doors and is costing the NHS hundreds of millions of pounds a year by scaring doctors from using cheap and effective medicines.”
In the US, surveys indicate that Avastin has about 60% of the market for ophthalmic use. The World Health Organization has also backed the drug for ophthalmic use, adding the drug to its ‘Essential Medicines’ List.