In the landmark case, Laboratoires CTRS v European Commission (Case T-452/14), the General Court of the European Union, by its judgment dated 11 June 2015, annulled the marketing authorisation for Kolbam (ASK Pharmaceuticals) in recognition of the orphan market exclusivity afforded to Orphacol (Laboratoires CTRS).

The General Court ruled that “the statements concerning the efficacy ofKolbam for the Orphacol therapeutic indications or for all inborn errors of primary bile acid synthesis, which are included in the SmPC and the assessment report [for Kolbam], are liable to facilitate the off-label prescribing of Kolbam for the Orphacol therapeutic indications and thus to give rise to circumvention of the market exclusivity attaching to Orphacol and, consequently, to render Article 8(1) of Regulation No 141/2000 ineffective.”


Laboratoires CTRS is the marketing authorisation holder of the orphan medicinal product Orphacol (cholic acid), which is authorised for the treatment of two very rare and serious genetic liver disorders. As an orphan medicinal product, Orphacol benefits from a 10-year period of market exclusivity pursuant to Article 8(1) of Regulation No 141/2000 (the “Orphan Regulation”), as of 16 September 2013. During this period, the regulatory authorities cannot grant a marketing authorisation (or accept any application) in respect of a similar medicinal product for the treatment of the same therapeutic indications.

On 4 April 2014, the Commission granted a marketing authorisation for another orphan medicinal product, Kolbam, for three therapeutic indications different to those for which Orphacol is authorised. However, the Summary of Product Characteristics (SmPC) and the Assessment Report for Kolbam wrongly contained extensive references to the efficacy as well as references to the safety of Kolbam in the therapeutic indications for which Orphacol is authorised.

The Kolbam SmPC and Assessment Report were liable to facilitate off-label prescribing in circumvention of Orphacol’s orphan market exclusivity

Off-label prescribing is not regulated by European law meaning that there is no provision preventing healthcare professionals from prescribing a medicinal product for therapeutic indications outside of those specified in the SmPC. However, the General Court today held that if the effectiveness of Article 8(1) of the Orphan Regulation is to be ensured, the off-label prescribing of a medicinal product for therapeutic indications covered by the market exclusivity attaching to another medicinal product by virtue of that provision should not be facilitated. To that end, the Commission should have ensured that the SmPC and Assessment Report for Kolbam was not formulated in a way that would induce healthcare professionals to prescribe Kolbam off-label in the indications for which Orphacol is indicated and benefits from orphan market exclusivity.

The General Court further acknowledged the arguments made on behalf of Laboratoires CTRS in relation to advertising. Specifically, since European legislation and jurisprudence allows for the advertisement to healthcare professionals of a medicinal product providing that it complies with the SmPC, the statements in the Kolbam SmPC relating to the safety and efficacy of Kolbam in the Orphacol indications could be used in advertisements to healthcare professionals, further facilitating the circumvention of the market exclusivity afforded to Orphacol.
In light of the above, and also confirming that the SmPC and Assessment Report are an integral part of the statement of reasons for the Commission Implementing Decision granting the marketing authorisation, the General Court annulled the marketing authorisation for Kolbam.


The General Court not only ruled in accordance with the letter of the law but also acknowledged the purpose of the 10-year period of orphan market exclusivity, which is to incentivise industry to invest in the development and marketing of orphan medicinal products. Even if the Commission will not implement the true meaning of the Orphan Regulation, the General Court will.