EU General Court clarifies interpretation of “satisfactory method” in the context of orphan medicinal products

In the recent case of Medac Gesellschaft für klinische Spezialpräparate mbH v European Commission, the EU General Court has annulled a decision of the European Commission in which it held that the applicant’s medicinal product Trecondi (treosulfan) did not satisfy the criteria for orphan designation under Regulation (EC) No. 141/2000 (the “Orphan Regulation”).

In order to achieve orphan status, a medicinal product must fulfil the criteria set out in Article 3(1) of the Orphan Regulation which relate to (a) the nature (and prevalence) of the disease it is intended to treat; and (b) how the product compares to existing methods of treatment for the particular condition which have already been authorised. In particular, in the context of the second limb it must be shown that there is no “satisfactory method” of diagnosis, prevention or treatment of the relevant condition, or, if such method does exist, that the new medicinal product will be of “significant benefit” to those affected by the condition.

Background

Trecondi is given to patients with malignant and non-malignant pathological conditions before a bone marrow transplant. It is used as part of a conditioning treatment to induce immunosuppression in the patient to prevent transplant failure; to eliminate as many malignant cells as possible; and to induce bone marrow suppression to clear the patient’s bone marrow and make room for the transplanted bone marrow cells.

Although the applicant had previously obtained an orphan designation for a potential treosulfan-based medicinal product in 2004, when the marketing authorisation for Trecondi was granted in 2019, the Commission held that the product should not be classified as an orphan product and the EU Register of Orphan Medicinal Products should be updated accordingly.

This decision was based on a recommendation from the Committee for Orphan Medicinal Products (COMP) that the orphan designation should not been maintained because although the applicant had established that Trecondi would be of significant benefit compared to certain existing products (bisulfan and thiotepa), it was not of significant benefit in comparison with melphalan- and cyclophosphamide-based medicinal products.

The applicant challenged this decision at the EU General Court. The case was decided without the need for oral proceedings.

Judgment

The applicant’s main plea was that the Commission had made a manifest error of law in its interpretation of the concept of a “satisfactory method” under Article 3(1)(b) of the Orphan Regulation. In particular, the applicant’s view was that melphalan- and cyclophosphamide-based medicinal products are not “satisfactory methods” for the treatment of the orphan condition for which Trecondi was authorised, and therefore should not have been taken into account when applying the orphan criteria. It was accepted between the parties that “off-label” use, i.e. use outside the indication in the Summary of Product Characteristics (SmPC) could not be taken into account when assessing satisfactory methods.

In its judgment, the Court conducted a systematic comparison of the relevant SmPCs, noting in particular that:

1. The SmPCs should be interpreted strictly because any variation to the SmPC, for example to add a new indication, would have to be assessed and authorised by the competent authority. Therefore, the marketing authorisation could not extend beyond the scope of the SmPC.
2. It was possible under Article 7(3) of the Orphan Regulation for a product to have both orphan and non-orphan indications, in which case separate marketing authorisations would be required.
3. The granted indication for Trecondi was different to the indication for the melphalan- and cyclophosphamide-based products. The melphalan- and cyclophosphamide-based products could only be used for patients with one of the conditions listed exhaustively in their respective SmPCs. Trecondi did not have this limitation – it could be used prior to HSC transplantation without restriction on the underlying condition for which treatment was sought. This meant that there were conditions for which Trecondi could be used in relation to which melphalan- and cyclophosphamide-based products were not authorised.
4. The products also differed in their target populations. While melphalan- and cyclophosphamide-based products were only authorised for use in children in relation to specific, limited conditions, Trecondi was authorised for all malignant pathological conditions in children over one month old. The Court considered that the divergences in use in the paediatric population should be awarded particular importance given the value placed on paediatric medicines (and the associated incentives) in EU legislation.

Overall, the Court concluded that Trecondi was authorised for conditions and patient populations which were not covered by the SmPCs of melphalan- and cyclophosphamide-based products. Accordingly, these products could not be considered to be “satisfactory methods” under Article 3(1)(b) of the Orphan Regulation, and the part of the Commission decision declining orphan status was annulled.

Given that Trecondi is not yet back on the Community register of orphan medicinal products, we expect that confirmation of its orphan status will be referred back to the COMP for determination following the comments of the EU General Court.

Comment

This case provides helpful – if not unsurprising – guidance on the significant benefit test for orphan products and in particular which existing treatments should be taken into account when assessing whether satisfactory methods already exist.

Cases on orphan designation have become more common in recent years, although usually with the outcome that the Commission decision is upheld rather than annulled. Given the value which can attach to an orphan designation – in particular, the extension of data exclusivity to 10 years – there is a real incentive for companies to initiate litigation where they disagree with the COMP or the Commission’s assessment of such rights.