On 22 March 2018, the General Court handed down its judgment in Shire Pharmaceuticals Ireland Ltd ("Shire") v European Medicines Agency ("EMA"), Case T-80/16. The case concerned the requirements for designation of a medicinal product as an orphan medicinal product. More specifically, it examined the impact of an earlier designation on a company's ability to obtain a new orphan designation for a medicinal product containing the same active substance as a previously authorised product.

We discuss the General Court's judgment in this article. The judgment is likely to have significant impact on incentivising research into rare diseases, and is a welcome decision for innovator companies conducting research into rare diseases, as well as the patients suffering from such diseases.

Facts

The case concerns the EMA's refusal to validate Shire's application for designation as an orphan medicinal product for Shire's idursulfase product that is delivered through intrathecal administration ("Idursulfase-IT"). Idursulfase-IT is used in the treatment of cognitive disorders which arise with Hunter Syndrome.

Idursulfase itself was designated an orphan medicinal product for the treatment of Hunter Syndrome in 2001, and Elaprase (a product containing the active substance idursulfase) was granted a marketing authorisation ("MA") in 2007. Regulation No 141/2000 (which governs orphan medicinal products), (the "Orphan Product Regulation") requires applications for orphan product designation to be submitted prior to applications for MAs.

Shire initially applied for orphan designation of its Idursulfase-IT product in 2013 on the basis that cognitive disorders arising with Hunter Syndrome constitute a distinct disease from Hunter Syndrome. The EMA disagreed, finding that it constituted a severe form of Hunter Syndrome, an indication which had already been granted an MA. It therefore refused to validate Shire's application, a process which is required prior to assessing whether a product meets the criteria for orphan medicinal product status.

Shire submitted another application in 2015, arguing that Idursulfase-IT was a new product that would provide a "significant benefit" to patients compared to existing treatments for Hunter Syndrome, namely in relation to its therapeutic effects, composition and means of administration. According to Article 3(1)(b) of the Orphan Product Regulation, a product which provides significant benefit to patients over existing treatments will be entitled to orphan medicinal product status despite the existence of a satisfactory method of treatment. However, the EMA again refused to validate the application on the basis that idursulfase had already been granted an orphan designation for the treatment of Hunter Syndrome in 2001 – the 2001 designation decision related to idursulfase generally, and as it did not specify a particular form of administration, Idursulfase-IT was therefore covered by the 2001 designation. This second refusal formed the subject matter of the General Court's decision.

The General Court's judgment

The General Court considered that the fact that Idursulfase-IT and Elaprase contain the same active substance does not mean that they are the same medicinal product – EU regulation defines them differently. On the facts of this case, Idursulfase-IT and Elaprase differ in composition, method of administration and therapeutic effects. Elaprase is not effective in treating cognitive disorders arising in patients suffering from Hunter Syndrome. The two products were therefore not the same medicinal products for the purposes of validating the application.

Important to the General Court's decision was the objective and scheme of the Orphan Product Regulation, i.e. the stimulation of the research, development and bringing to market of medications used to treat rare diseases. It did not consider that the wording or context of the regulation prevented an application for an orphan medicinal product where the medicinal product contained the same active substance as another authorised product, provided that the sponsor (in this case Shire) can satisfy the second criteria of Article 3(1)(b), referred to above.

The concept of "significant benefit" set out in Article 3(1)(b), according to EU Commission communications, may include a more convenient formulation or route compared to an authorised medicinal product, even where that product has the same active substance and is intended to treat the same condition. The basis of Shire's 2015 application was the significant benefit of Idursulfase-IT in relation to its therapeutic effects, composition and means of administration.

In relation to whether the general nature of the 2001 orphan designation covered Idursulfase-IT, the General Court acknowledged that applications for designation as an orphan medicinal product are submitted at an early stage of product development, and prior to any decisions on the marketing of such products. The 2001 designation led to the development of Elaprase. Using the broad nature of a designation formulated in the early stages of development of a medicinal product to prevent subsequent requests for designations of new products containing the same active substance would go against the objective and general scheme of the Orphan Product Regulation.

The General Court therefore annulled the EMA's decision not to validate Shire's application, concluding that the EMA's arguments would deprive Shire of the opportunity to demonstrate that its product provides significant benefit to patients.

The purpose of the Orphan Product Regulation is to incentivise research into, and development of treatments for rare diseases to ensure that patients suffering from rare conditions have access to the same quality of treatment as other patients.

With its decision, the General Court offers welcome clarification on when medicinal products should be granted orphan designation status in cases where medicinal products contain the same active substance, and in particular what constitutes "significant benefit". It confirms the importance of the objective of the Orphan Product Regulation when considering whether a medicinal product qualifies for orphan designation. Moreover, it acknowledges that the commercial reality of developing orphan medicinal products means that designations may be formulated generically, but that should not prevent further designations from being granted where the same active substance is involved. It has also showed that, at the very least, sponsors should be given the opportunity to demonstrate that products provide a significant benefit to patients suffering from rare diseases.

As explained above, this is a welcome decision for both patients suffering from these diseases, as well as companies involved in developing treatments, especially when such development involves the same active substance that nevertheless is beneficial to patients.

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"Important to the General Court's decision was the objective and scheme of the Orphan Product Regulation, i.e. the stimulation of the research, development and bringing to market of medications used to treat rare diseases."