EMA Highlights: Drug watchdog’s hands are tied in off-label prescribing spat

by Gary Finnegan: The European Medicines Agency (EMA) says its powers are limited when it comes to regulating off-label use of licensed medicines. The watchdog is at the centre of a long-running row that has come to a head in Italy after a series of adverse events in patients given a cancer drug to treat an eye condition.

Reports from Italian media say five patients suffered eye infections following off-label treatments at a hospital in Careggi, Florence, prompting an internal inquiry to find the source of infection.

Cost-conscious national authorities in several EU countries have been allowing the off-label use of Avastin (bevacizumab) – a drug approved for several cancers – to treat people with age-related macular degeneration (AMD).

This has proven controversial as there are licensed medicines for AMD in Europe which are available in most countries. However, these are believed to be significantly more expensive than Avastin.

The drugs in question are all monoclonal antibodies which target the same cell growth mechanisms. Experts say they are biochemical cousins; similar but not the same.

Another key difference is packaging. While drugs approved for AMD are sold in single-use sterile doses, the cancer drug comes in larger volumes and must be prepared by pharmacists if they are to be used for AMD patients. Critics say that even top pharmacists with excellent facilities cannot completely eliminate the risk of infection during this process.

This is not the only medical condition where off-label alternatives are used instead of licensed products but the case has become a focal point for research-based pharmaceutical companies.

Three organisations representing the pharma and biotech sector – EFPIA, Europabio and Eucope – wrote to the European Commission earlier this year claiming that the Italian authorities were “undermining key elements of the EU pharmaceutical regime, in particular the marketing authorisation system”.

The European Medicines Agency routinely collects information on all adverse events – including those that occur in relation to off-label use – but cannot advise governments on which drugs to reimburse.

“In the case of Avastin, the product information was changed in July 2012 to update warnings related to its unlicensed intravitreal use in eye conditions,” a spokesperson said. The warning says that direct injection into the eye can increase the risk of infection, bleeding in the eye, raised eye pressure and compromised vision.

The update followed adverse events reported after “unapproved intravitreal use of Avastin compounded from vials approved for intravenous administration in cancer patients”, according to the EMA.

However, the agency said it cannot comment on off-label use where a licensed product is available “as this mainly involves issues revolving around reimbursement and pricing, which do not fall into the remit” of the EMA.

The row highlights the tensions between Brussels and national authorities when it comes to health policy and drug prices. While the EU has a key role in regulating medicines, decisions on their approval and use are made by Member States.