As we reported in last June’s edition of the Health legal update, the National Institute for Health and Clinical Excellence (NICE) has been asked by the Department of Health (DH) to look into the possibility of appraising the clinical and cost effectiveness of bevacizumab (Avastin) to treat wet age-related macular degeneration, the leading cause of blindness in the UK, and other conditions affecting the eye.

NICE has now published a report of its findings: Exploratory work of bevacizumab in eye conditions.

Bevacizumab is an “anti-VEGF” drug, licensed for the treatment of cancer, which inhibits the blood supply to the tumour. The use of bevacizumab in the eye (to stop the untrammelled proliferation of weak, unstable blood vessels which burst and cause damage) is considered to constitute an “unlicensed”, rather than an “off-label” use of the drug, because the splitting of the product into vials of suitable volume for intraocular injection changes the volume and method of administration and creates an unlicensed product. Normally NICE would only appraise a drug for use within its licensed indications. The only VEGF inhibitor licensed to treat wet AMD is ranibizumab (Lucentis), a comparatively expensive drug. There are no licensed VEGF inhibitors for the treatment of non-AMD eye conditions. Bevacizumab, whilst chemically related to ranibizumab, is significantly less expensive and its routine use therefore has the potential to generate considerable costs savings for the NHS. At the moment, however, there is variation in both the inclination of clinicians to use the cheaper drug and the criteria set by primary care trusts to fund it. Access is therefore determined largely by the postcode lottery.

The report reveals that the principal concerns of the stakeholders (patient groups, NHS bodies, professional groups, pharmaceutical companies and the DH), not surprisingly, centred upon patient safety regarding the use of a drug lacking the “safety guarantee” of a licence. The known side effects and contraindications have been determined using studies where bevacizumab has been administered by a different route and in larger volumes. The drug is also known to be associated with an increased risk of stroke, and possible systemic toxicity, in people with cancer. Concerns were also raised about the absence of a central organisation to oversee standards of manufacture and the potential for variation in the techniques of preparation.

The report concludes that there are unknown safety risks associated with the intravitreal use of bevacizumab, and that these must be quantified, using data from existing records of the drug in clinical use. Moreover, it would be important for provision to be made for setting up and maintaining safety registers, tracking the origin of a batch and undertaking safety reviews and post marketing surveillance.

Notwithstanding these concerns, there was overall support for an appraisal of intra-vitreal bevacizumab. Stakeholders agreed that an appraisal would need to be conditional upon, or incorporate the assessment of, the safety and quality of intra-vitreal bevacizumab by a regulatory body or through the involvement of regulatory expertise. Arrangements for safety monitoring and pharmacovigilance would also need to be explored.

The next step is for the DH to decide whether or not to refer bevacizumab to NICE for consideration as part of its technology appraisal process.