On 22 March 2018, the European General Court handed down its judgment in Case T-80/16 Shire Pharmaceuticals Ireland v EMA.  Shire had sought annulment of the EMA’s decision refusing to validate its 2015 application for designation of its medicinal product Indursulfase-IT as an orphan medicinal product for the treatment of Hunter Syndrome. This decision is particularly important for innovator companies who invest in R&D for rare diseases, and will likely have an impact on incentivizing this type of research.


In 2001, a Shire product containing the active substance idursulfase was designated as an orphan medicinal product for the treatment of Hunter Syndrome. This was followed in 2007 by the grant of a marketing authorisation for the medicinal product Elaprase, containing the active substance idursulfase, and administered as a solution for intravenous infusion. In parallel, Shire started developing another medicinal product containing the same active substance. However this product, Idursulfase-IT, could be delivered intrathecally, whereas Elaprase did not cross the blood-brain barrier. Intrathecal administration of the new product allowed treatment of cognitive disorders associated with a severe form of Hunter Syndrome.

Application for orphan designation for Idursulfase-IT

In 2015 Shire applied for orphan designation of Idursulfase-IT on the basis that, within the meaning of Article 3(1)(b) of Regulation No 141/2000 (Orphan Regulation), Idursulfase-IT would provide a “significant benefit” to patients with Hunter Syndrome compared to existing treatments, including Elaprase. The EMA refused to validate the application, arguing that an application for designation had to be made before grant of a marketing authorisation and Elaprase, also manufactured by Shire and containing the same active substance, had already been granted a marketing authorization. The EMA argued that the 2001 designation referred in general terms to idursulfase without specifying a particular form of administration. Accordingly, Idursulfase-IT was covered by that initial designation and the EMA maintained that Shire should not benefit from an additional period of market exclusivity for the second authorised indication of a designated orphan condition.


The General Court annulled the EMA’s decision not to validate the 2015 application, and dismissed all of the EMA’s and the Commission’s arguments. In its judgment, the General Court examined some of the criteria for the designation of an orphan medicinal product, finding that:

    1. The validation stage of an application for orphan designation is purely procedural – the EMA was obliged to validate the application as it was submitted before an application for marketing authorisation for Idursulfase-IT, and it was accompanied by the requisite documents. It was inappropriate to assess the differences between Elaprase and Idursulfase-IT at the validation stage.
    2. The concept of an ‘active substance’ is distinct from the concept of a ‘medicinal product’ – the General Court agreed with Shire that the EMA and the Commission had incorrectly applied the concept of ‘active substance’; both products contain the same active substance, but this did not necessarily mean that they were the same medicinal product. In this case, Elaprase differs from Idursulfase-IT in its composition, method of administration, and therapeutic effect.
    3. A sponsor may apply for orphan designation for a product containing the same active substance as another product authorised in its own name and for the same indication – as long as the company can demonstrate that the medicinal product provides a “significant benefit” compared to other available products. The General Court noted that a significant benefit could be demonstrated in different ways, including through a more convenient formulation or route of administration. It also noted that particular benefits for a sub-set of the relevant patient population could constitute a “significant benefit” under the legislation.
    4. A similar medicinal product with the same active substance developed later may be able to obtain an independent 10 year orphan market exclusivity period although the EMA argued that the possible ‘duplication’ of market exclusivity would lead to misuse of the provisions of the Orphan Regulation and would be contrary to its purpose, the General Court took a different view. It found that it was not inconsistent with the objective and scheme of the Orphan Regulation, that patients suffering from rare diseases should have access to an alternative medicine that gave them the prospect of a significant benefit compared to a previously authorised product. That was the case even if the same company had developed both the new and the previously authorised product.


This decision will be welcomed by innovators. At a time when the European Commission has been revising its guidance seemingly with a view to restricting the circumstances in which market exclusivity under the Orphan Regulation will be granted, it indicates that this may sometimes not be achievable without amendment to the primary legislation.