An advocate general of the European Court of Justice has said EU pharmaceutical regulations don’t block member states’ health services from reimbursing drugs used for off-label indications in the interests of limiting the cost to national insurers.
The 25 July opinion (in French) by advocate general Henrik Saugmandsgaard Øe addressed questions from an Italian court hearing a case between a local subsidiary of Swiss drugmaker Novartis and the Italian medicines agency (AIFA).
Novartis holds a marketing authorisation for Lucentis, a drug used to treat retinal condition age-related macular degeneration (AMD), which is included on a list of treatments that are reimbursable by Italy’s national health service (SSN).
In 2014 – in accordance with an opinion handed down by Italy’s superior council of health, an advisory body to the country’s health ministry – the AIFA added rival pharma company Roche’s oncology drug Avastin to the AMD list, despite the fact that its marketing authorisation doesn’t cover the indication. According to the superior council’s decision, a bottle of Lucentis cost the SSN €902 compared to just €82 for a bottle of Avastin, leading the referring court to assume that it was motivated by a desire to reduce costs.
Novartis challenged the AIFA’s decision, claiming the two national laws on which it was based infringed EU-wide Directive 2001/83/EC. The directive holds that medicines can’t be placed on the market in member states without marketing authorisations, unless they are “prepared in a pharmacy in accordance with a medical prescription for an individual patient (commonly known as the magistral formula),” which Novartis claimed was not the case with the off-label prescription of Avastin.
The AIFA responded that the use of Avastin to treat AMD, which requires the repacking of the drug from its original vial into several single-use syringes containing 0.1 ml, does not have an industrial character and qualifies as a “magistral formula” under Directive 2001/83. In addition, AIFA pointed out that member states are allowed to derogate from the directive “in accordance with legislation in force and to fulfil special needs” to approve the provision of treatments “formulated in accordance with the specifications of an authorised health care professional and for use by his individual patients on his direct personal responsibility.”
The Italian Council of State referred the dispute to the ECJ, asking whether Directive 2001/83 allowed the AIFA to rely on national laws to add Avastin to the AMD treatment list as a way of keeping the SSN’s costs down, even though it was an off-label indication for the drug and Lucentis was already on the market.
Øe noted that the Treaty on the Functioning of the European Union empowered individual member states to regulate and manage their own health services, including the pricing of medicines and their inclusion within the scope of national health insurance systems. He also pointed to ECJ caselaw which holds that member states retain the power to regulate the conditions under which doctors can prescribe medications.
However, Øe pointed out that the ECJ had also consistently held that member states had to exercise these powers in accordance with EU law. As such, he said, there was nothing to stop the SSN reimbursing an off-label indication for a drug as long as it was manufactured and marketed in compliance with EU pharma regulations.
This raised the question of whether Avastin, when repackaged for the treatment of AMD, should be considered as a new drug requiring its own marketing authorisation under Directive 2001/83.
Øe noted that the repackaging process, while it involved changes to dosage, conditioning and the route of administration of Avastin, didn’t change the substance itself. As such, he said, the drug would remain subject to the same pharmacovigilance system established by Directive 2001/83, and the AIFA was not prevented from adding it to the AMD list. This was true even in the current case, where the sole reason for the off-label use of a drug was to reduce costs for the national health insurance scheme, and where there was already an alternative treatment on the market, he concluded.