Commission’s rejection of medicine results in imbroglio
By Ophélie Spanneut | Friday 11 May 2012
The European Commission has refused to authorise the placing on the market of a medicine used to treat an orphan disease, in spite of the positive opinion of scientific experts and the member states, which have given their opinion on two occasions. A legal imbroglio has resulted.
TREATMENT OF ORPHAN DISEASE
Orphacol is a medicine developed to treat a life-threatening orphan disease affecting the liver (there are 90 cases in Europe). The active substance was developed through university-hospital research at the Paris public hospital system (Assistance Publique des Hôpitaux). Discovered in 1992 and used as a hospital formulation since then, it has been used to treat 19 patients in Europe. In 2007, the Paris public hospital system transferred its rights to the French laboratory, CTRS.
To receive authorisation to market the medicine, CTRS submitted an application to the European Medicines Agency (EMA) in October 2009.
Under the procedure in force (Regulation 2004/726), the Commission decides whether or not to issue marketing authorisation after obtaining a positive opinion from the EMA and the approval of member states.
In December 2010, the EMA adopted a positive opinion. It even described Orphacol as a medicine of significant public interest. At the Commission’s request, the EMA adopted a second opinion, in April 2011, also positive. The member states were then consulted through the standing committee. On two separate occasions – first on 13 October 2011 and again on 8 November 2011 in the appeal committee – they vetoed the Commission’s request for rejection of market authorisation on grounds of an incomplete application. The member states’ opposition prohibits the Commission from adopting its decision, in this case to reject marketing authorisation, but the executive is nevertheless not obliged to take the opposite decision, ie to issue marketing authorisation. To sum up this Kafkaesque situation, the Commission cannot refuse marketing authorisation but on the other hand is not obliged to issue it either.
In January 2012, the laboratory initiated an action before the EU court system for failure to act. Its case is based on the fact that the Commission has failed to act although, according to the regulation, it is supposed to adopt a final decision within 15 days following the consultation by the standing committee. The EU General Court agreed to apply an accelerated procedure and even advanced the hearing by several weeks, an extremely rare occurrence. At the public hearing, on 24 April, the judges were stunned by this case, as
GROUNDS FOR REFUSAL
In use for nearly 20 years, Orphacol can be given a waiver from the ordinary market authorisation procedure justified by “well established medical use”. Directive 2001/83 exempts the applicant from providing the results of toxicological, pharmacological and clinical tests if it is possible to prove that the medicine has been used in the EU with recognised effectiveness and an acceptable level of safety for at least ten years. The application must nevertheless be substantiated by a detailed scientific bibliography. The European Medicines Agency and the Commission have different views on these points. The executive considers that the application is not substantiated by sufficient data and that well established medical use cannot be recognised based solely on the experience of its use as a hospital formulation. The EMA, on the other hand, finds that the data lead to the conclusion that the benefit-to-risk ratio is positive. The member state representatives, reinforced by the EMA’s position, highlight the interest of patients in the face of the legal arguments used by the Commission.
TEST OF STRENGTH
On 23 April, the eve of the hearing, the Commission announced that it had convened the standing committee for another meeting, on 8 May, to submit its proposal for a negative decision. In an unexpected turn of events, at this third review the states failed to rally a qualified majority to oppose the Commission’s decision. Italy and Spain did not vote.
Before the Lisbon Treaty came into force, in cases of disagreement between the Commission and the member states, the decision was handed over to the Council, which could override the Commission. With the new comitology rules, however, the Orphacol case demonstrates the Commission’s supremacy. According to a diplomat, “the member states, meeting in the appeal committee, have only a veto power and cannot replace the Commission”. But a veto of a refusal of marketing authorisation is not equal to authorisation.
Three member states have joined the laboratory’s appeal: France, the Czech Republic and the United Kingdom. The 8 May vote reshuffles the cards, however. The Commission now has the possibility to refuse marketing authorisation.
A number of questions remain. On comitology, can the Commission start the procedure over indefinitely by convening member states whenever the appeal committee result does not suit it? This is what the lawyers of the states supporting the appeal denounce in their arguments, that the Commission can convene the states until it gets the result it wants.
The General Court’s ruling is expected to bring answers in the instant case.
Clinical tests or not
Antoine Ferry, head of CTRS, explains that conducting a new clinical programme on patients treated with Orphacol, as suggested in the Commission’s arguments, would infringe the principle of medical ethics. It would entail taking the medicine away from patients, placing their lives in danger.
The Commission nevertheless refers to a study conducted by the Cincinnati Children’s Hospital Medical Center, to argue that wider clinical studies are possible despite the low number of patients. Ferry finds this reference surprising. He notes that the study does not meet European quality standards and that comparison is not possible because the American study concerns seven pathologies whereas Orphacol has only two therapeutic indications. The number of cases is therefore not the same.