Judgement of 23.09.2020, Case T-549/19 concerning the assessment, granting and maintenance of an Orphan Drug Status
I. Background of the procedure
In February 2004, a treosulfan-containing medicinal product for conditioning therapy prior to allogeneic hematopoietic stem cell transplantation was designated as an orphan medicinal product and entered in the orphan drug registry (so-called orphan drug status).
By decision of June 20, 2019, the Commission approved Treosulfan (Trecondi®) for this indication without maintaining the orphan drug status. The Commission decided that Treosulfan (Trecondi®) would no longer fulfil the criteria as an orphan medicinal product according to Art. 3 of Regulation (EC) No. 141/2000 (Regulation 141/2000) as Treosulfan (Trecondi®) would not be of significant benefit compared to melphalan- and cyclophosphamide-containing medicinal products, which were generally considered to be satisfactory methods.
On August 8, 2019, a lawsuit and an application for interim relief was filed at the European Court. The application for interim relief was rejected by decision of September 26, 2020, which was confirmed by decision of February 26, 2020, by the ECJ.
In the main action, the Court of First Instance has granted the application and annulled the Commission’s decision not to maintain the orphan drug status.
Preu Bohlig represented the claimant in the lawsuit and the procedure for granting interim legal protection since July 2019. The lawsuit and the procedure for granting interim legal protection were managed and processed jointly by our partners Peter v. Czettritz and Dr. Alexander Meier.
II. The key statements
The Commission took the view that a partial overlap of the indications concerned was sufficient to constitute a satisfactory method in general terms within the meaning of Article 3 of the Regulation. The Court of First Instance gave a clear rejection and followed Preu Bohlig’s argumentation that the marketing authorisation and the summary of product characteristics defines the scope of a medicinal product. A medicinal product can only be classified as a satisfactory method in comparison to a medicinal product for which an application for a marketing authorisation as an orphan medicinal product has been submitted if and to the extent that it is authorised for the same orphan indication. The scope of the respective marketing authorisation and so-called summary of product characteristics of a medicinal product, which must be interpreted strictly, are decisive in this respect.
Accordingly, the off-label use of a medicinal product cannot be considered a satisfactory method. Information on paediatric target populations is of particular importance in determining whether and to what extent a satisfactory method exists.
III. The decision of the court
In recitals 49-90, the Court of First Instance dealt in detail with the five pleas in law put forward in the action, which is why the contested Commission Decision C (2019) 4858 final, by which the medicinal product treosulfan (Trecondi®) was not classified as an orphan medicinal product, must be annulled.
The court clearly states in recital 52 regarding the interpretation of the requirements of Regulation 141/2000:
” … that a medicinal product can be classified as a ‘satisfactory method’ within the meaning of Article 3(1)(b) of Regulation No 141/2000 only if it is authorised in the Union or in a Member State of the Union for the same orphan indication”.
In recitals 55-59, the Court addresses the meaning of the marketing authorisation of a medicinal product and the related summary of product characteristics. In this respect, the Court deals in recitals 58-60 with the off-label use of a medicinal product and makes it very clear that it cannot be considered as having been authorised and, accordingly, off-label use is not considered a satisfactory method within the meaning of Article 3(1) of Regulation 141/2000. In recital 62, the Court then concludes that the summary of the characteristics of a medicinal product can only be interpreted narrowly.
The competent authority must, before granting a marketing authorisation and also in connection with the amendments or extensions of an existing marketing authorisation, on the basis of the documents and particulars submitted by the sponsor, verify that the efficacy benefits of the medicinal product outweigh the potential risks. In addition, the European legislator wishes the Authority to be able to analyse, on the basis of quality, safety and efficacy criteria, the risk-benefit balance of all medicinal products when they are placed on the market, when they are renewed and when they are authorised, and whenever the competent authority considers it appropriate. For this reason, all amendments and extensions to an existing marketing authorization must also be approved or included in the initial authorization, and the holder of an already authorized medicinal product is obliged to keep the product information of his medicinal product up to date with the latest scientific knowledge.
Accordingly, according to the court in recital 64, it follows from this that a change in the summary of product characteristics is not a formality at all, but rather that each such change requires an additional examination of the risk-benefit ratio.
If the medicinal product covered by the application for orphan medicinal product authorisation is intended for the diagnosis, prevention or treatment of diseases or patient populations for which the reference medicinal products are not authorised, even if only partially, according to their respective summaries of characteristics, these reference medicinal products are not to that extent to be considered as “satisfactory methods” for those diseases or patient populations (recital 66).
In recitals 67 and 68, the Court of First Instance states that any other consideration would be contrary to the objectives of Regulation 141/2000 to create incentives for the research, development and marketing of medicinal products for diseases that are so rare that the pharmaceutical industry is not very inclined to develop medicinal products. It would be contrary to this objective to exclude a potential medicinal product from the benefits of Regulation 141/2000 on the sole ground that “satisfactory methods” exist for some of the orphan diseases for which the medicinal product is intended.
Encouragingly clear, the Court underlines the importance that the legislator attaches to the availability of paediatric medicinal products and makes the following clear statement in recital 76: “Consequently, the information on the paediatric target populations in the summary of product characteristics of the medicinal products compared is of particular importance, also in the context of the assessment of whether a satisfactory method within the meaning of Article 3(1)(b) of Regulation 141/2000 exists”.
With regard to treosulfan (Trecondi®), the Court of First Instance therefore concluded in recitals 80 and 81 that melphalan- and cyclophosphamide-based medicinal products already authorised can only be regarded as a satisfactory method to the extent that they are also authorised in relation to diseases and target populations.
Despite a partial overlap, these drugs are not approved for the diseases and target populations not covered by the summary of product characteristics and therefore cannot be considered as a “satisfactory method” for these diseases and target populations.
With this ruling, the Court of First Instance has followed the argumentation of Preu Bohlig and has pleasingly clearly emphasized the importance of the approval and the content of the technical information, which is also reviewed and approved by the approval authorities.
IV. Conclusion
Thus, the decisive factor in determining whether a satisfactory method according to Art. 3(1) of Regulation 141/2000 exists is the summary of characteristics of the medicinal product applied for and the reference medicinal products in relation to diseases and target populations. Partial overlaps between diseases and target populations are not such as to deprive the medicinal product of the benefits of the Regulation. For the non-overlapping diseases and patients, the reference medicinal product cannot be considered as a satisfactory method and a separate marketing authorisation with orphan drug status can be obtained.
Beyond the case decided, the ruling therefore has fundamental significance for the future assessment, granting and maintenance of an orphan drug status, especially in the field of development of paediatric medicinal products.
