New Italian rules which allow off-label drug use to be reimbursed by the national health service for economic reasons will undermine the European Union (EU) regulatory framework, “potentially compromising patient safety and creating legal uncertainty,” industry leaders have warned.

Under the new law, Italy’s medicines agency AIFA will now, in some cases, permit off-label drug use to be reimbursed even if an alternative authorised treatment is available. Previously, such use was reimbursable only if the product was included in AIFA’s approved drug list and where no alternative authorised treatment was available.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) has condemned AIFA’s endorsement, under the new law, of the off-label use of Genentech/Roche’s Avastin (bevacizumab) in its decision to reimburse the drug for use in the eye, pointing out that on-label treatments are currently available to Italian patients.

“We are concerned about efforts by EU member states creating secondary, national marketing authorisations for economic reasons that undermine the EU regulatory framework and could potentially put patients at risk,” said EFPIA director general Richard Bergstrom.

“These medicines have not been tested and assessed to the same stringent standards for the off-label indication, putting patients’ health and safety at risk for the sake of cost savings,” he added.

And the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE) points out that, in a 2012 case, the Court of Justice of the EU clearly underlined that exceptions to the marketing authorisation requirement have to be interpreted narrowly, and that financial considerations in themselves cannot justify such an exemption.

“Despite this unambiguous case law, the new Italian law directly promotes the non-authorised use of a product for purely financial reasons,” says EUCOPE.

And EFPIA’s Richard Bergstrom warned: “promotion of economic-driven off-label use will discourage pharmaceutical companies from undergoing the costly and time-consuming authorisation process for new indications if public authorities favour off-label use of other, cheaper medicines which have not undergone the same stringent safety and efficacy assessment.” 

Life sciences expert Paul Ransom of law firm Pinsent Masons points to the UK case of Aventis and Novartis’ Lucentis (ranibizumab) where the off-label use of a lower-priced drug was evaluated against an on-label use of a higher-priced drug.

It was concluded that the two drugs were equally effective in treating wet age-related macular degeneration (AMD), and four NHS bodies in England initially used Avastin, the off-label but cheaper treatment for the condition. However, they changed their practice after Novartis lowered its prices for use of Lucentis, says Mr Ransome.