On 11 June 2015, the General Court of the Court of Justice of the European Union issued its judgment in the case between Laboratoires CTRS and the European Commission concerning market exclusivity for orphan medicinal products (Case T-452/14).

This case addresses orphan market exclusivity concerning two medicinal products approved for the treatment of rare liver disorders: Orphacol and Kolbam. The EU General Court annuls the European Commission's decision by which a marketing authorisation ("MA") was granted for Kolbam, on the basis that it results in a circumvention of the orphan market exclusivity for Orphacol. Although the therapeutic indications for which Kolbam is authorised are different from the therapeutic indications for which Orphacol is authorised, the EU General Court considers that statements concerning the efficacy of Kolbam for the therapeutic indications of Orphacol which are included in Kolbam's approved product information and assessment report, are liable to facilitate the off-label prescribing of Kolbam for those Orphacol indications. The EU General Court concludes that this gives rise to circumvention of the market exclusivity attaching to Orphacol and renders Article 8(1) of the EU Orphan Regulation (EC) No 141/2000 (the "Orphan Regulation") ineffective.

Legal framework

The EU Orphan Regulation provides in Article 8(1) that where a MA is granted for a medicinal product that has been designated as an orphan medicinal product, for a period of 10 years, no MA application shall be accepted and no MA shall be granted for the same therapeutic indication in respect of a similar medicinal product. Article 8(3) of the Orphan Regulation contains a derogation from the orphan market exclusivity in the event a second, similar, medicinal product is demonstrated to be clinically superior.

Factual Background

The company Laboratoires CTRS holds a MA for the medicinal product Orphacol, whose active ingredient is cholic acid. Orphacol was designated as an orphan medicinal product. Orphacol is approved for the therapeutic indication of the treatment of inborn errors in primary bile acid synthesis due to two types of enzyme defects. In 2012, the European Commission had refused to grant MA for Orphacol. Laboratoires CTRS appealed the refusal decision and the EU General Court annulled the decision refusing the MA in its judgment of 4 July 2013 (Case T-301/12). Subsequently, the European Commission adopted a decision on 12 September 2013, granting a MA for Orphacol (Cholic Acid).

The company ASK Pharmaceuticals GmbH holds a MA for the medicinal product Kolbam (previously known as Cholic Acid FGK), also with cholic acid as the active ingredient. Kolbam was also designated as an orphan medicinal product. The MA application for Kolbam related to the therapeutic indication of the treatment of inborn errors in primary bile acid synthesis due to five types of enzyme defects, including the two types of enzyme defects for which Orphacol is authorised. As Orphacol was approved prior to Kolbam, the orphan market exclusivity for Orphacol prevented the approval of Kolbam for the therapeutic indication related to those two types of enzyme defects. The applicant sought to rely on the derogation to orphan exclusivity under Article 8(3) of the Orphan Regulation, arguing that Kolbam was clinically superior to Orphacol. The European Medicines Agency's scientific committee (CHMP) however concluded that Kolbam was not clinically superior to Orphacol in those two indications. Orphacol's orphan market exclusivity was thus not set aside. Therefore, Kolbam was only approved for the therapeutic indication of the treatment of primary bile acid synthesis due to three other types of enzyme defects.

Nevertheless, the Summary of Product Characteristics ("SmPC") and the European Public Assessment Report for Kolbam contain extensive reference to the efficacy and safety of Kolbam in the therapeutic indications for which Orphacol was authorised.

Laboratoires CTRS appealed the European Commission's decision granting a MA for Kolbam on the grounds that this circumvented Orphacol's orphan market exclusivity, since the terms upon which the MA for Kolbam was granted imply, in substance, that Kolbam is also authorised for the two therapeutic indications for which Orphacol is authorised. Laboratoires CTRS maintained that the scope of the Kolbam MA is broader than that of the Kolbam therapeutic indications because of the references in the SmPC and the assessment report to the efficacy of Kolbam for the Orphacol therapeutic indications.

The European Commission took the position that there could be no breach of Orphacol's orphan market exclusivity, as the MA for Kolbam was not granted for the Orphacol therapeutic indications.

Judgment

The EU General Court considers that in order to ensure the effectiveness of Article 8(1) of the Orphan Regulation (which provides for the orphan market exclusivity of Orphacol) the off-label prescription of Kolbam for therapeutic indications covered by the orphan exclusivity of Orphacol should not be facilitated.  This is even more so considering that off-label prescription is not prohibited or even regulated by EU law. Therefore the European Commission should ensure that a MA for a medicinal product is not formulated as such that it may induce a physician to prescribe a medicinal product for therapeutic indications other than those covered by the MA and for which a MA has already been granted for another medicinal product that benefits from orphan market exclusivity. Such would amount to a circumvention of orphan market exclusivity.

The EU General Court considers that the statements relating to the efficacy of Kolbam for the Orphacol therapeutic indications, which are found in the SmPC and assessment report, are liable to render Article 8(1) of the Orphan Regulation ineffective and to undermine the market exclusivity which Orphacol enjoys under that provision.

The EU General Court considers that Kolbam and Orphacol are different medicinal products, authorised for different therapeutic indications which correspond to different diseases afflicting different patients. On that basis, it was considered that it was not necessary (and thus there was no justification) to include statements as to the efficacy of Kolbam for the Orphacol therapeutic indications.
The European Commission argued that the contested statements in Kolbam's assessment report should be considered as relevant scientific information which should be mentioned. The EU General Court however considers that the European Commission is not prevented from including certain scientific data, including clinical data, in the assessment report, but that this does not justify any statement in the assessment report regarding the efficacy of Kolbam for therapeutic indications that are not covered by the approved therapeutic indications of Kolbam and that are included in the MA for Orphacol which is protected by orphan market exclusivity. The EU General Court acknowledged that the SmPC must contain information that is relevant to the prescribing physician, but that accordingly, statements relating to the efficacy of the medicinal product concerned for therapeutic indications other than those approved does not form part of the information required by the EMA's Guideline on SmPCs.

The European Commission had also argued that the statements regarding the efficacy of Kolbam for the Orphacol therapeutic indications should be included in the SmPC on the basis of the EU Paediatric Regulation (EC) No 1901/2006, which in brief requires that the results of paediatric studies shall be included in the SmPC. The EU General Court also dismisses that argument, considering that a presentation of the results of the paediatric studies does not require a conclusion to be drawn on the efficacy of the product for therapeutic indications for which Kolbam has not been authorised and for which another product (Orphacol) has been granted MA and enjoys orphan market exclusivity.