What is stopping the NHS from using bevacizumab for macular degeneration and other retinal disorders?

Financial implications

The IVAN study found that using bevacizumab instead of ranibizumab to treat neovascular AMD would save NHS England £102m (€128m; $160m) a year.5 In the US switching to bevacizumab would save nearly $29bn over 10 years without substantially altering patient outcomes.6 Therefore switching to bevacizumab seems an obvious way to minimise costs in this time of austerity. Furthermore, there are other retinal conditions for which the best treatment is vascular endothelial growth factor inhibitors. These include retinal vein occlusions and diabetic macular oedema. NICE has also approved ranibizumab for these conditions. The evidence base is, as yet, not so strong for bevacizumab in these diseases, but it is likely that it will be shown to be effective, again at a much cheaper cost.

All vascular endothelial growth factor inhibitors need to be given repeatedly over many years. In the context of an ageing population, the drug costs to the NHS can be expected to escalate exponentially.

In 2011, after the CATT study was published, the Royal College of Ophthalmologists stated: “The college believes that the NHS executive should urgently instruct NICE and the Medicines and Healthcare Products Regulatory Agency (MHRA) to evaluate the use of Avastin in the treatment of AMD and produce national guidelines for the use of anti-VEGF agents in AMD.”7 That call was ignored.

Obstacles to using bevacizumab

Commissioners are expected to enact NICE guidance, and NICE has not considered bevacizumab. This makes it difficult to commission the use of bevacizumab and to deprive patients of NICE sanctioned treatment. Furthermore, the General Medical Council (GMC) states that doctors should prescribe unlicensed drugs only if “there is no suitably licensed medicine that will meet the patient’s need.”8 Without unequivocal GMC and NICE support, ophthalmologists are understandably concerned that they may be assuming unacceptable personal liability by using an unlicensed drug when a licensed alternative exists. Where these concerns don’t exist, ophthalmologists are happy to prescribe bevacizumab. For example, bevacizumab is the market leading drug for neovascular AMD in the US.9 Closer to home, in Guernsey, where NICE guidance does not apply, bevacizumab is the only therapy commissioned for the treatment of neovascular AMD.

To change treatment in the UK NICE must appraise bevacizumab along with licensed drugs for the treatment of neovascular AMD. Other vascular endothelial growth factor inhibitors do not necessarily need to be excluded because, for example, some patients may benefit from a switch from one to another and aflibercept has a practical advantage in that it can be given at two monthly instead of monthly intervals.10 Therefore there should still be the option of using alternatives to bevacizumab if they are in the patient’s best interest. Until bevacizumab has been appraised the GMC must also be unambiguous in supporting doctors who use the off-label drug instead of licensed alternatives.

There are reasons why NICE has not considered bevacizumab. The same company Roche makes ranibizumab and bevacizumab (Novartis has marketing rights outside the US for ranibizumab) so there is little financial incentive for Roche to pursue NICE appraisal for bevacizumab or to have it licensed for use in neovascular AMD.11 12 Therefore in this unprecedented situation, either the regulators must find a way to licence a drug without the sponsorship of the company that owns it or NICE must find a way to consider an off-label drug that is not being submitted for appraisal by its owners. Bevacizumab could then be used routinely in the UK, saving the NHS millions of pounds a year.

The hospital eye service is facing a serious and ever increasing capacity problem because of the demand for frequent intravitreal injections. Consequently, patients may not be getting treatment when they need it and not getting the best results. The money saved by switching to bevacizumab could facilitate investment in these services. Given the overwhelming evidence for the effectiveness and safety of bevacizumab in the treatment of neovascular AMD, central government should act to overcome the bureaucratic hurdles that prevent its use.