La publication of the official proposal by the European Commission is scheduled for 29 March 2023, but during the World Evidence, Pricing and Access Congress - EPA Congress - Thomas Bols, Head of Government Affairs and Patient Advocacy, EMEA and APAC of PTC Therapeutics, Inc. points of major change and impact concerning the Orphan Drug Regulation.
The Regulation currently in force has brought several successes recognised by all stakeholders: pharmaceutical companies, patient groups and policy makers.
They were also found to be:
- Strong increase in the number of drugs for rare diseases
- OMPs (Orphan Medicines) have developed several areas of significant unmet need
- Substantial increase in clinical trials
- Improved speed to market
- Increased use of protocol assistance (scientific advice available to developers of orphan drugs for rare diseases).
The reasons for the revision of the Orphan Medicinal Products Regulation are manifold:
- Political pressure: the 'market failures' of some drugs that were withdrawn after their authorisation, high prices, uneven access between member states and lack of transparency
- Implementation of new technologies: gene and cell therapies, GMOs, etc.
- Reorganisation of legislation: there is a need to combine and rationalise a number of scattered pieces of legislation (e.g. LPG) relating to this matter
The key topics are:
1) Designation 'Orphan': a possible comparison with off-label drugs and clinical practice is also expected.
2) Orphan market exclusivityif it meets a high unmet medical need the drug will have a market exclusivity of 10 years, otherwise 9 years (for orphan drugs today it is 10). Generally for non-orphan drugs it is 5 years.
3) Market launch conditions (and incentives): the product should be issued and supplied continuously and in sufficient quantity to cover the needs of patients in the EU Member States where the marketing authorisation is valid. In order to receive the extension [sic] the marketing authorisation holder must apply [sic] between the 34th and 36th month or for SMEs between the 46th and 48th month after the date of initial marketing. Launch in all 27 EU Member States (unless the Member State opts out) will give an extra year of exclusivity.
To apply, applicants will have to provide documentation from the Member States confirming compliance with the conditions or waiver of the conditions
The Member State issues a confirmation of compliance, a declaration of non-compliance or provides a waiver, within 60 days of the marketing authorisation holder's request.
4) Maximum unmet therapeutic need HUMN: the EMA develops scientific guidelines for the application of what constitutes a maximum unmet therapeutic need, after consultation with the European Commission and the parties involved in the cooperation mechanism.
Assuming that all orphan medicinal products (OMPs) are already designated as responding to unmet medical needs, the new definition recalls those that respond to the greatest therapeutic need.
To qualify as such, the product must significantly reduce morbidity or mortality for a relevant part of the population
With regard to these important changes, these main critical issues were found:
- Orphan designation. Due to the added risk of off-label comparisons and denial of orphan designation. There may be unintended consequences of the definition of 'significant benefit'.
- Orphan market exclusivity A shorter period of market exclusivity for an orphan drug that does not fulfil the criteria of highly unmet therapeutic needs reduces the incentives previously granted to drugs with orphan status, which could have an impact on research and negotiations in countries.
- Market launch conditionality. These are potentially onerous requirements for the market exclusivity of an orphan drug. Expectations are unrealistic for small and medium-sized companies and for ATMP orphan drugs.
- Unmet therapeutic need: it is unclear what is meant by 'relevant patient population' in the draft regulation, as well as who will decide which products meet this criterion.
