Use of bevacizumab in common and rare eye diseases
University of Southampton research has led to the use of the cancer drug bevacizumab as an alternative and more cost-effective treatment for age-related macular degeneration. Our research has underpinned new clinical policy guidelines and was used in a successful judicial review, which paved the way for the drug to be used by the NHS.
Additionally, bevacizumab has been identified as the first ever treatment for Sorsby fundus dystrophy, a rare juvenile form of macular degeneration.
Overview
Context
Age-related macular degeneration (AMD) is a common condition of the eye that usually first affects people in their 50s and 60s and causes progressive loss of central vision. There are nearly 700,000 cases in the UK.
The licensed treatments in the UK and EU for the rapid-onset form of AMD, known as ‘wet AMD’, are ocular injections of drugs that block growth of the fragile blood vessels. These cost around £700 per patient per injection.
In 2007, Southampton Professor of Ophthalmology Andrew Lotery reported effective use of a cheaper alternative treatment, the cancer drug bevacizumab, costing around £50 per patient per injection.
Professor Lotery played a key role in the subsequent trial and campaigning required for bevacizumab to become approved for use in wet AMD in the UK.
Research challenge
The NIHR-funded IVAN trial (2007-2013) was the first randomised, controlled trial to compare the cancer drug bevacizumab to a more expensive licensed drug, ranibizumab, in the treatment of wet AMD. It involved 610 patients from eye clinics across the UK, with a significant number of patients recruited from Professor Lotery’s Southampton clinic.
The trial demonstrated that bevacizumab was equally as effective as ranibizumab in targeting retinal blood vessels and managing wet AMD.
Further research led by Professor Lotery identified bevacizumab as the first ever treatment for Sorsby fundus dystrophy, a rare juvenile form of macular degeneration. The treatment is subsequently being used in the NHS for the first time.
Influence on WHO guidelines
Based on major clinical trials including the IVAN study, in October 2013 the World Health Organisation included bevacizumab in its essential medicine list for the treatment of AMD and continued to include it in its revised lists thereafter.
Influence on policy and guidelines of the General Medical Council and NICE
Southampton research and Professor Lotery’s role as Chair of the Scientific Committee of the Royal College of Ophthalmologists (RCO) were instrumental in assisting NHS Clinical Commissioning Groups (CCGs) to campaign for use of the cheaper drug for wet AMD.
On 23 January 2018, NICE published guideline NG82 on AMD, recognising the effectiveness of bevacizumab. On the same day, the General Medical Council released a statement acknowledging the NICE guidelines and support from the RCO.
Influence on NHS policy and defence of subsequent legal challenge
In late 2017, a group of twelve NHS CCGs in the North West introduced a policy to offer patients diagnosed with wet AMD the choice of bevacizumab as preferred treatment.
Prof Andrew Lotery. Genetic investigation of AMD.
The policy was met with legal action from Bayer plc and Novartis Pharmaceuticals UK Ltd, who held UK marketing authorisations for ophthalmic use of the two more expensive licenced drugs for wet AMD. The companies argued that the CCGs’ use of bevacizumab, sold as Avastin by Roche, to treat wet AMD went against EU law because Roche holds no marketing authorisation for ophthalmic use.
Professor Lotery acted as the single expert witness for the CCGs in the judicial review that followed. The case went in favour of the CCGs, with Professor Lotery’s evidence listed in the judgement.
In March 2020, following an appeal by the pharmaceutical companies, the judgement was upheld, paving the way for the use of bevacizumab in treating AMD in the NHS.
Ophthalmologists from University Hospital Southampton calculated a potential saving to the NHS of £449 million per year if all injections used bevacizumab. In 2019, Southampton clinicians administered 540 bevacizumab doses, saving approximately £243,000.
Bevacizumab for the treatment of Sorsby fundus dystrophy
Following the discovery by Professor Lotery’s team of bevacizumab as the first ever treatment for Sorsby fundus dystrophy, blindness has been prevented in five patients. It is now an accepted treatment at Southampton, and the team have provided the evidence base for this treatment to be used elsewhere in the NHS for this small but deeply affected patient group.
