This comment article highlights the controversy that exists in the choice for anti-VEGF drugs used for treatment of macular oedema and wet age-related macular degeneration (AMD). Two existing licensed drugs for macular oedema are ranibizumab (Lucentis) and aflibercept (Eylea). A third drug, bevacizumab (Avastin), is only licensed for colorectal cancer, and therefore, use in the eye is ‘off label’. Yet, independently supported randomised controlled trials, and systematic reviews were unable to find a significant difference in their safety or efficacy. The cost difference is, however, significant. Prices, according to the British National Formulary (BNF), are: ranibizumab £742 per single injection vial; aflibercept £816 per single injection vial; bevacizumab £242.66 per vial, but in practice each bevacizumab vial is divided into 20 injections, giving a price of £12.13 per injection. In each case, these costs are multiplied many times because patients require repeated injections. A total of 189 FOI requests were sent to all UK NHS ophthalmic units for the number of ranibizumab, aflibercept and bevacizumab injections prescribed during January 2015. The results indicated the anti-VEGF injection cost to the NHS; the vast majority (97%) were with the more expensive drugs of ranibizumab and aflibercept. If all injections used divided bevacizumab, the estimated cost would be £607,749 (£729,500 incl. VAT) saving the NHS £449,196,354 (£539,035,492 incl. VAT) per year.
The hurdle remains, since General Medical Council (GMC) guidelines state that “Prescribing unlicensed medicines may be necessary where: There is no suitably licensed medicine that will meet the patient’s need…/ Or where a suitably licensed medicine that would meet the patient’s need is not available.” It is agreed that licensing prevents companies marketing drugs without evidence of safety. Also, since bevacizumab vials could be divided in the clinic, in a non-regulated environment, there is greater chance of infection, contamination or incorrect dosage. However, it could be argued that arms of the same company produce bevacizumab and ranibizumab. Genentech (San Francisco, CA, USA), a subsidiary of Roche (Basel, Switzerland), markets ranibizumab in the USA and bevacizumab worldwide. Novartis (Basel, Switzerland), a major shareholder in Roche, markets ranibizumab outside the USA and it seems there is no financial incentive for a company producing one expensive and licenced drug for macular oedema, to licence another one of its cheaper drug. In a cost-effective environment, for healthcare the world over, bevacizumab remains a popular choice. The ability to change practice rests with advisors and those with the purchasing power.
GMC guidance states that clinicians must provide effective treatments based on the best available evidence, and must make good use of resources. A core remit of the National Institute for Health and Care Excellence (NICE) is to ensure NHS treatments are cost-effective. The Royal College of Ophthalmologists has stated: “There is clear evidence that, despite the lack of a licence, Avastin is a safe and effective drug for the treatment of neovascular AMD. The College would therefore welcome an urgent review of this issue by the United Kingdom Health Regulatory Bodies to consider how this unusual situation can be remedied.” One possible solution could be for NICE / Medicines and Healthcare Products Regulatory Agency (MHRA) to initiate licensing themselves, preserving quality control for bevacizumab preparation while saving hundreds of millions of pounds of NHS budget.