Intended for healthcare professionals


Health ministers may call for appraisal of unlicensed cancer drug for eye treatment

BMJ 2011; 342 doi: (Published 06 January 2011) Cite this as: BMJ 2011;342:d62
  1. Nigel Hawkes
  1. 1London

Health ministers in England are considering calling for a full technical appraisal of a cancer drug to treat eye conditions, even though it is unlicensed for the indication.

Bevacizumab (Avastin) has been widely used in the US and the UK to treat the wet form of age related macular degeneration, despite its lack of a licence, because it is much cheaper than the licensed product ranibizumab (Lucentis). Both were originally developed by Genentech, part of Roche, and ranibizumab has been approved for NHS use by the National Institute for Health and Clinical Excellence (NICE). Both share a common mode of action, inhibiting blood vessel growth.

Bevacizumab is around 15 times cheaper than ranibizumab, if it is bought as a cancer drug and then split into many separate doses for injection into the eye. But Roche has no desire to apply for a licence because it would be undercutting its own more expensive alternative, which is marketed in the UK by Novartis.

The last UK Government asked NICE to examine the issues and provide advice. It published its findings early in December, concluding that there was support among interested parties for a full appraisal which would need to incorporate an assessment of the safety and quality of bevacizumab by a regulatory body, or through regulatory expertise. And since Roche would not be responsible for monitoring the use of the drug, special arrangements for safety monitoring would need to be implemented.

It is now up to ministers to decide if they want NICE to complete a full appraisal. A Department of Health spokeswoman said this week that they were considering the issue with input from the Medicines and Healthcare products Regulatory Agency (MHRA).

Although it is not unprecedented for NICE to be asked to review unlicensed or off label medicines, the MHRA generally sets its face against the use of such products when licensed alternatives are available.

Several clinical trials of bevacizumab in eye conditions have been carried out or are in progress, according to a report commissioned from Southampton Health Technology Assessments Centre. The team there identified 50 published trials, including 40 randomised clinical trials, and another 12 ongoing trials, including five randomised clinical trials in the UK.

These include dosing trials and a 600 patient head to head comparison with ranibizumab in age related macular degeneration (the IVAN trial), which is due to report in September this year. A similar study (CATT) involving 1200 patients is being carried out in the US and is expected to report in the first quarter of this year.

The NICE report concludes that IVAN and CATT will provide sufficient clinical evidence, though they may be under powered to detect all adverse events. It recommended that a full appraisal should be conducted, but doing so without any MHRA involvement would risk undermining the regulator. Accordingly it recommended an appraisal that involves the MHRA or its expertise in some way.

Even if positive, such an appraisal would leave doctors in a difficult position, since the drug would remain unlicensed and they might face actions for negligence if anything went wrong. The same could also apply to those who supply the medicine—Moorfields Eye Hospital in London and the Royal Liverpool and Broadgreen University Hospital. The Liverpool pharmacy, which is supplying the IVAN trial, is producing 7000 doses a year at around £50 (€59; $78) per dose, compared with £750 per dose for ranibizumab.

The main losers if unlicensed use of bevacizumab is allowed in the UK would be Novartis, which can be expected to lobby against any such move. The attitude of the present government is hard to predict. It was not responsible for requesting the NICE studies, and has its own ideas about how to make drug companies set prices that more nearly reflect the value of their products.


Cite this as: BMJ 2011;342:d62

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