General Court annuls the Commission’s decision refusing to grant a marketing authorisation for Orphacol
On 4 July the General Court of the European Union (“GC”) ruled in case T-301/12 as regards the grant of the Marketing Authorisation (“MA”) of Orphacol, a cholic acid-based orphan medicinal product which is used to treat two rare but very serious liver disorders (the “Medicinal Product”). Specifically, the GC upheld the application filed by the Medicinal Product development company Laboratoires CTRS (the “Applicant”), for annulment of European Commission (“EC”) decision of 25 May 2012 refusing an MA for the Medicinal Product despite the positive opinion issued by the Committee for Medicinal Products for Human Use (the “CMPHU”) of the European Medicines Agency (“EMA”).
The case falls within the scope of directive 2001/83/EC, relating to medicinal products for human use, as amended by directive 2004/27/EC (the “Directive”), which states that, as a rule, any MA application must be accompanied by the results of the pre-clinical tests and clinical trials of the medicinal product concerned (Article 8(3)(i)). However, pursuant to Article 10bis of the Directive, the applicant is not required to provide such results – to be replaced by appropriate scientific literature – if he can demonstrate that the active substances of the medicinal product a) have been in “well-established medicinal use within the Community for at least 10 years” and b) have “recognised efficacy and an acceptable level of safety”. In light of these requirements, which were met by Orphacol according to the Applicant, the EC instead denied the MA stating that, on the one hand, no well-established medicinal use of the active substance (cholic acid) was demonstrated and, on the other hand, no comprehensive data regarding the efficacy or the safety of the medicinal product was enclosed.
In response to the first objection, the GC holds that, as regards orphan medicinal products (used to treat rare and serious diseases), the well-established medicinal use can refer – by way of derogation – to the use provided by Article 5(1) of the Directive, which concerns medicinal products supplied to fulfill “special needs” in response to “a bona fide unsolicited order, formulated in accordance with the specifications of an authorised healthcare professional and for use by one or more individual patients under his direct personal responsibility”. In this case, cholic acid was used as hospital preparation to treat patients in France between 1993 and 2007, and, always in France, since that date cholic acid capsules were authorised for use under the brand name Orphacol according to the French Public Health Code, to be issued to a “named individual patient for compassionate use”. Contrary to the EC decision, the GC holds that such use constituted well-established medicinal use pursuant to the abovementioned provisions and, in particular, evidence of the use of the hospital preparations for “special needs” in response to “a bona fide unsolicited order” as per Article 5(1) of the Directive, provided that they were supplied “in response to situations justified by medical considerations” and were “necessary to meet patients’ needs”, as well as “prescribed by a doctor as a result of an actual examination of his patients and on the basis of solely therapeutic considerations”.
As regards the second argument of the EC, the GC reminds that both Article 22 of the Directive and Article 14(8) of Regulation 726/04 (on procedures for obtaining an MA) provide that an MA may be granted in “exceptional circumstances” even if data regarding the efficacy and safety are lacking, provided that the applicant can show that he is unable to provide comprehensive data based on one of the grounds set out in Annex I to the Directive.
According to the GC, in the Orphacol case the Applicant actually showed to be unable to provide comprehensive information on the efficacy and safety of the medicinal product based on those grounds, namely: i) the objective rareness of the treated disorders; ii) the fact that it would be impossible – as per the assessment of the CMPHU which was not challenged by the EC – to carry out clinical trials, because participation in them would expose patients to the risk of serious damage, or even death; iii) the fact that a controlled study of the efficacy of cholic acid would be contrary to the principles of medical ethics because it would involve dividing the patients into two groups, one receiving the treatment on trial and the other receiving a placebo. Furthermore, the GC notes that Part II-1(c) of Annex I to the Directive provides for the possibility of an MA being granted even where information is missing, “as long as the demonstration of an acceptable level of safety and/or efficacy can be supported although some studies are lacking”. According to the GC, such demonstration had been given in the present case.
In light of – inter alia – the above, the GC annulled EC Implementing Decision C(2012) 3306 of 25 May 2012 refusing an MA for Orphacol.