EU proposals for new pharmaceutical legislation: proposed changes to stimulate R&D of orphan medicines

Rare diseases are medical conditions which occur in no more than 1 in 2,000 individuals. Between 6,000 to 8,000 different rare diseases affect around 36 million patients in the European Union. Many of these diseases are genetic and manifest in childhood. The European Union enacted its first legislative act in the field of rare diseases in 1999 – Regulation (EC) No 141/2000 on Orphan Medicinal Products (the Orphan Regulation) – to stimulate research and development (R&D) for medicines for rare diseases. These medicines are also known as orphan medicines.

In April 2023, the European Commission published proposals for a new Regulation and Directive in pharmaceutical policy (referred to as the new general pharmaceutical legislation). The revision of the general pharmaceutical legislation has been put forward in the context of insufficient patient access to medicinal products, supply issues and pharmaceutical shortages in EU/EEA countries, and a lack of focus on ensuring R&D focuses on areas of unmet medical need.

Under these new proposals, the existing EU Orphan Regulation will be repealed in its entirety and replaced by provisions contained within the new proposals. The proposals have not been adopted yet (they remain to be discussed by the European Parliament and European Council). However, the proposals recognise that rare diseases require specific requirements and incentives to stimulate R&D. The following changes are proposed to support R&D of orphan medicines, accompanied by initial reactions to these elements from stakeholders or commentators in the field.

The proposed legislative changes

1. A modular approach to market exclusivity

Generic/biosimilar medicines for the same indication as a product currently under patent cannot be placed on the market during market exclusivity periods. These periods are in place to allow the R&D investment in developing the product, which is often very high for orphan medicines, to be recouped.

The market exclusivity period under the Orphan Regulation was 10 years. The proposals put forward a modular approach to market exclusivity which will see the baseline period reduced to 9 years. However, additional 1-year periods are available if certain criteria are met, for (up to) a maximum of 13 years of protection. The European Union finds this approach will stimulate pharmaceutical R&D by addressing areas of high unmet medical need (HUMN) by rewarding innovation in disease areas with no current treatment or medicinal products that are exceptional advances, while also promoting faster generic/biosimilar competition where possible to improve access and affordability of orphan medicines.

EURORDIS, the European patient organisation for rare diseases, has welcomed the modular aspect to encourage R&D in areas of unmet need. However, other stakeholders or commentators have raised concerns around the attainability of the maximum 13-year protection period if the requirements for the additional periods of protection prove too difficult.

2. The introduction of a ‘high unmet medical need’ criterion

The proposals seek to direct R&D to where it is most needed and where investment may be less likely under regular market forces; the proposals define this as areas of high unmet medical need. Under the proposals, medicines which address high unmet medical need can obtain an additional year of market exclusivity (see the 1-year periods discussed above). The Regulation provides a definition for HUMN, to be supplemented by additional scientific guidelines once the proposals are accepted.

The European Society for Paediatric Oncology (SIOP Europe) and Childhood Cancer International (CCI Europe) have endorsed the inclusion of HUMN in the proposals. However, industry stakeholders have indicated that a fixed definition may be problematic given that the effectiveness of orphan medicines varies across patients and within diseases with differences in symptom severity. Not only this, but the exploratory nature of R&D means that early development stages may not be able to provide proof of a ‘meaningful reduction’ or establish that the investment and result will eventually address HUMN.

3. Amendments to regulatory data protection periods

Generic or biosimilar manufacturers may not make use of, or refer to, the (pre-) clinical data used by the marketing authorisation holder to obtain approval for their patented product until regulatory data protection periods have passed. Generic manufacturers need this data for the development and approval of generic medicines of the patented product in question.

The proposals seek to reduce the period of regulatory data protection from eight to six years with options for extension in specific circumstances, such as an EU-wide launch. A reduction in this period is aimed at decreasing the time generic (or biosimilar) medicines take to enter the market by granting quicker access to (pre-) clinical data. Improving market availability of generics can have positive impacts for the affordability of medicines, as generic medicines are most often cheaper than their patented equivalent. This has been welcomed by SIOP Europe and CCI Europe, which highlight the positive effects on equality in access to medicines resulting from an EU-wide launch. However, the European Federation of Pharmaceutical Industries and Associations (EFPIA) raised concerns that the reduction of these periods will negatively affect the competitiveness and innovative power of the European Union, with more profound effects for small and medium-sized enterprises (SMEs).

4. Changes to the orphan designation

The ‘orphan designation’ is a status used by the European Medicines Agency (EMA). If awarded, the applicant is eligible for more assistance or advice in their application for marketing authorisation for that product, as well as fee reductions/waivers.

The proposals introduce an expiration date to the validity of the orphan designation: now the product would lose the designation and the associated benefits after seven years, where it was previously not subject to a time cap. The European Commission expects this provision will stimulate product development to be completed within this time period, and thereby improving availability and access for patients.

Some stakeholders have suggested that companies already reduce the duration of R&D as far as possible within the requirements of the regulatory system and that companies will simply apply for orphan designation at a later stage.

5. Changes to the EMA Committee on Orphan Medicinal Products

The proposals also seek to remove the EMA’s dedicated Committee on Orphan Medicinal Products, responsible for recommending which medicines are eligible to receive orphan designation by the EMA. The Committee’s expertise is proposed to be reorganised into working groups or expert pools which assist the EMA.

In conclusion

It remains to be seen in what shape and form these proposed provisions for orphan medicines are included in the eventual legislation, if and when adopted. However, given the importance of addressing rare diseases and the major changes that are proposed, the European Commission and relevant stakeholders will need to closely observe the implementation and effects of the legislation.

Read more about challenges for the diagnosis and treatment of rare diseases and the European Union’s action in this area in our study ‘Tackling rare diseases: Challenges, opportunities and gaps for action on rare diseases in the European Union’, produced for the European Parliament.