The NHS has won a major legal battle over the pharmaceutical industry in the UK High Court. It is likely to a have a significant impact on patients with wet age-related macular degeneration (AMD).
It was discovered a decade ago that off-label bevacizumab – sold under the trade name Avastin – was also effective at treating certain eye conditions. This was confirmed by a number of international clinical trials and is also accepted by the World Health Organisation (WHO). Drugs licensed for ophthalmic use, such as Lucentis, are made from the same molecule as Avastin but command a far higher price.
Last week, the High Court ruled in favour of 12 NHS clinical commissioning groups (CCGs), allowing them to offer patients Avastin to treat wet-AMD, the leading cause of vision loss in the UK.
The CCGs, all based in the north of England, had been embroiled in the legal dispute with the companies Novartis and Bayer – who make drugs licensed specifically for treating wet-AMD – since November last year after deciding to offer off-label Avastin to their patients.
Legal proceedings were initiated by the companies on four grounds – that the supply of Avastin was unlawful as it was not licenced for ophthalmic use, went against drug regulation, undermined NICE approved drugs and that patient information was misleading.
The decision by the High Court in favour of the CCGs could mean huge savings for the NHS. An injection of Lucentis or Eylea – the licenced drugs for wet-AMD produced by Novartis and Bayer, respectively – costs between £500-800. Avastin costs as little as £28.
Estimates of annual savings to the NHS following the ruling are around £100m. It has been estimated by one health economist that had the decision been made a decade ago, it could have saved the NHS between £2-3bn.
The Royal College of Ophthalmologists (RCOphth) has campaigned for the use of Avastin since 2012. Its scientific chair, Prof Andrew Lotery, said it was a ‘great day for the NHS and patients’ and that RCOphth members ‘can now feel assured that they can offer the best treatment for their patient’s individual needs’.
‘We expect that the release of funds in the use of Avastin will be secured to improve patient care within the hospital eye service,’ he added.
However, Mike Burdon (pictured), president of the RCOphth, added: ‘The ruling will not lead to an immediate large scale saving for the NHS because significant infrastructure, equipment and staffing issues will have to be addressed to ensure service delivery. But, by continuing to engage with commissioners and the health care bodies in all four nations, the predicted savings are achievable and which should be invested back into the hospital eye service.’
Dr David Hambleton, chief of South Tyneside CCG, one of the 12 involved in the case, called the ruling a ‘victory for common sense over commercial interests’.
He said: ‘The drug is undeniably, equally effective, and much less expensive, and the money this will save – in excess of £13.5m per year for the 12 CCGs involved in this litigation alone, and hundreds of millions of pounds across the country – can be ploughed straight back into delivering the very best care possible to our patients.
‘Here in the North, that’s enough to pay for an extra 270 nurses or 266 heart transplants every year, and in a financially stretched NHS that could be life-changing for thousands of our patients.’
Dr Lawrence Gnanaraj, consultant ophthalmologist and clinical director at the Sunderland Eye Infirmary that treats thousands of AMD patients in the North East, said: ‘Today’s decision is very positive news not only for our patients here in Sunderland and the North East, but potentially across the whole NHS.
‘As clinicians, we understand the importance of ensuring value for money for the NHS and we have supported the introduction of a policy across the North East and north Cumbria which not only offers increased patient choice, but also has the potential to substantially reduce costs for the NHS which can be reinvested directly back into patient care.’
According to a report by GlobalData, a data and analytics company, half of patients with wet-AMD are prescribed Avastin in the US. The company said: ‘Avastin is a much cheaper alternative, costing only a small fraction of the approved drugs for wet AMD treatment, less than £400 a year per patient; however, the UK government ruled out the routine use of Avastin in 2015.’
No prohibition on prescribing
The 2015 ruling highlighted another issue – lobbying. A British Medical Journal (BMJ) investigation found that doctors had been discouraged from prescribing Avastin by pharma companies, Meanwhile, only this year European courts found Novartis and Roche, which makes Avastin but also sells the licence to produce Lucentis to Novartis, guilty of anti-competitive behaviour and spreading misinformation about Avastin to Italian doctors.
For some, this has brought the integrity of the General Medical Council (GMC) and Medicines and Healthcare Products Regulatory Agency (MHRA) into focus. Healthcare journalist Deborah Cohen claimed: ‘Both deterred use of an off-label drug, such as Avastin, on the grounds of cost. Both maintained they were following the law. Both had been lobbied.’
In a 2015 article for BMJ, she said: ‘The BMJ has learned that both the Association of the British Pharmaceutical Industry (ABPI) and the MHRA, acting on behalf of the government, lobbied against the proposed new clause [to allow the use of off-label Avastin on cost grounds].
‘Documents obtained under a freedom of information request show that the GMC consulted the ABPI and the MHRA on the matter, and continued to negotiate with both organisations after the consultation period had closed in May 2011.’
The GMC told Optician: ‘The GMC’s guidance reflects our understanding of the legal position. It says doctors should usually prescribe the medication licensed for a particular indication – but it does not prohibit doctors from prescribing unlicensed drugs simply because there is a licensed alternative. The judgment (Bayer & Novartis v North East CCGs) concluded that our guidance did not deter the use of off-label drugs.’
It did not, however, comment directly on the lobbying claims, adding: ‘Since the publication of our prescribing guidance in 2013 a number of organisations have made representations to us about their views on how our guidance should be interpreted. We responded by explaining the key points of the guidance – in particular that, although the guidance says doctors should usually prescribe licensed medicines in accordance with the terms of their licence, there were circumstances where they may prescribe unlicensed medications.
‘The judgment is clear that our guidance could not be seen as a prohibition on prescribing Avastin. And that our January 2018 statement puts that beyond doubt.’
‘It is important that the regulatory bodies such as the GMC and the MHRA now reflect on the best ophthalmic practice in the light of this ruling and the previous supporting guidance from NICE,’ said RCOphth’s Burdon. ‘Licensing laws are designed to protect patients from poorly regulated and unproven drugs. As recently as January, NICE guidance concluded that there was “no clinically significant differences in effectiveness and safety” between Avastin and the current licensed drugs.’
‘Following the publication of NICE’s guidance in January, which clarified that there are no clinically significant differences in the effectiveness and safety of medications that are licensed for treating AMD and those that are not licensed, we were also able to provide additional reassurance to doctors,’ added the GMC.
The newly won ability to use Avastin to treat wet-AMD comes with some additional challenges, however. Patients being treated with Avastin may require more injections than if they were being given Lucentis or Eylea, meaning more pressure on hospital eye services.
Ruling a ‘setback’
As might be expected, the pharma companies were highly critical of the ruling.
Roche said: ‘We firmly support a physician’s right to make an informed choice of medication for their patients, that patients should be informed and give consent that they are receiving an unapproved product and understand the risks/benefits associated with it. However, we believe the unapproved use of medicines for purely economic reasons breaches established laws governing the unapproved or unlicensed use of medicines.’
Meanwhile, Bayer said: ‘The ruling prioritises the cost of medication over doctors’ clinical judgement and expertise, as well as over the regulatory assessment of a medicine’s quality, efficacy and safety.
‘A service using this product [Avastin] risks increasing the number of clinic visits and injections a patient needs for proper monitoring of their conditions and for sight-saving treatment, placing more strain on NHS services and the already stretched workload of NHS staff. Bayer believes the ruling is a setback for public health.’
It intends to appeal against the judgement as it ‘has the potential to set a worrying precedent that denies patients the protection afforded by the regulatory process’.
‘Bayer’s appeal will focus on two principal issues: our firm view that supply of unlicensed bevacizumab as envisaged by the policy is unlawful; and our belief that the policy undermines the comprehensive licensing regime for medicines across the EU,’ it added.
Despite these criticisms, optical bodies welcome the ruling. A statement by the RCOphth added: ‘It is critical that trusts work with their clinicians and commissioners to ensure that any further increase in demand on the hospital eye service – predicted to increase by 50% over the next 20 years – can be strategically planned to continue to deliver efficient and high-quality care for patients.
‘While the ruling will be welcomed by all ophthalmologists in all four home nations, the hospital eye service remains seriously under-resourced in staff, equipment and infrastructure to deliver a safe and effective service, including the treatment of wet AMD.’
Jo Mullin, from the College of Optometrists, said: ‘We welcome the fact that the availability of an effective and cheaper drug will give those caring for patients with AMD a choice of treatments. We hope that the money saved will be reinvested in eye care.’
RNIB policy and campaigns manager, Helen Lee, said she welcomed the ‘clarity provided’ by the review but that she was ‘concerned that patients will be anxious about what this means for their treatment’.
‘It is critical each patient has the opportunity to have a full discussion with their clinician to give consent prior to switching or embarking on treatment,’ said Lee. ‘We know that some patients are permanently losing vision due to delayed and cancelled eye care appointments as services are struggling to cope with demand, so all savings generated by providing Avastin rather than licensed anti-VEGF drugs must be invested in eye care services.’