PARIS, Jan 2 (APM) - France has published new conditions under which a drug can be used off-label even when an alternative exists - an amendment to the temporary use recommendations (RTUs) drawn up in response to the Lucentis-Avastin debate in age-related macular degeneration (AMD).

The Official Journal (JO) on Wednesday published a decree setting out the new conditions under which RTUs may now be set up, following the extension of the scope of this tool within the amended social security funding law (LFSS rectificative) for 2014.

The text, almost identical to the draft released in August (APMMA 39373), came into force on Thursday, Jan 1.

The RTU was first set up in law on December 29, 2011, to allow authorised off-label prescribing of named products under special monitoring conditions, when no therapeutic alternative exists. A list of RTUs is drawn up by France’s drugs regulator ANSM. The amended law now means even drugs with alternatives may be considered.

The government attempted to widen the scope of this provision in the LFSS for 2013 by authorising use for public health reasons or in case of impact on health insurance finances. However, this failed owing to hostility on the part of the Council of State to the “economic RTU” section.

The new social security funding law for 2014 modified the legislation for RTUs via an amendment based on European case law.

It is expected that off-label prescription regulated by an RTU is possible, “in the absence of a drug with the same active substance, same dose, same pharmaceutical form with a marketing authorisation (AMM) or temporary authorisation (ATU) in the indication or conditions of use under consideration”.

This means that even if a drug is already approved in a particular indication, an RTU for another drug becomes possible.

The amendment specifically aims to allow use and reimbursement of Roche’s cancer drug Avastin (bevacizumab) in age-related macular degeneration (AMD). It is not approved in this indication but is widely used off-label, namely because it costs much less than the approached option, Novartis’ Lucentis (ranibizumab).

The application decree published on Wednesday allows implementing the changes, originally criticised by pharma, contained in the amended LFSS.

According to the text, the public health code will be modified to state that the purpose of the RTU is the “prescription of a drug not in compliance with its marketing authorisation (AMM) by a prescriber that in order to fulfil special needs of the patient, assessed through examination, and based on purely therapeutic considerations specific to the latter, prescribes the drug for the patient in the form and dose the prescriber considers appropriate”.

It emphasises that this applies “in the absence of a drug with the same active principle, the same pharmaceutical form and same dose, with an AMM in the indication or conditions of use under consideration”.

Further, the decree re-states the arrangements for monitoring the RTU. The agreement signed between ANSM and the pharma company requesting an RTU is deleted. Only the patient monitoring protocol and conditions for collecting information on the RTU, remains and has been added to.

The protocol should “inform on the role of each party intervening in patient follow up and particularly that of the prescribers and pharmacists and of the marketing authorisation holder or of the company that exploits it and that has been appointed for this purpose by the holder”.

Prescribers and pharmacists are bound to take part in collecting information. The recommendation may authorise the company to entrust patient follow-up, in whole or in part, to another company by means of a written contract.

Further, the decree sets out that the marketing authorisation holders or the pharma companies exploiting them shall distribute the initial RTU and every update to the prescribers. Measures taken for this distribution are subject to the prior opinion of ANSM and “shall not constitute an advertisement”.

In November, ANSM said it hoped to issue an opinion of the RTU concerning Avastin in AMD in the first six months of 2015 (APMMA 40370).

(Journal officiel of December 31, text 80)

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