The draft Regulation results in changes to the incentives available to the Sponsors of orphan medicine drug development to increase the focus on areas of high unmet medical needs and enhance generic and biosimilar competition. Another major change relates to the new powers of the European Medicines Agency (“EMA”) regarding orphan designations.
Orphan designation criteria
The proposal maintains the prevalence criterion of less than five affected persons per 10,000. However, there may be situations now where the EMA can alter this figure if appropriate to the condition or for other scientific reasons. This is intended to include rare conditions with short duration and high mortality.
The definition of significant benefit has been tightened and the clinically relevant advantage or a major contribution to patient care will only be recognised “if such an advantage or contribution benefits a substantial part of the target population”.
Orphan designation procedure
The draft Regulation will give the EMA powers to adopt decisions granting, refusing, and transferring an orphan designation, after consulting the Committee for Medicinal Products for Human Use (“CHMP”) or one of its working parties, but the consultation is optional. This aligns with the replacement of the Committee for Orphan Medicinal Products (“COMP”) by one or more new working parties.
Another major change relates to the validity of the orphan designation which will expire after seven years; this may be extended based on a “justified request” basis, with evidence of ongoing studies and intent to submit a future marketing authorisation (“MA”) application. This is designed to incite faster development and authorisation of designated orphan products but may result in orphan designation applications later in the development process.
Duration of market exclusivity
The draft Regulation introduces a new concept of a modulated market exclusivity to incentivise orphan medicines development for high unmet medical needs, ensure market predictability and fairer distribution of incentives.
Products are considered to address a high unmet medical need if:
There is no authorised medicine for the condition, or the new product brings exceptional therapeutic advancement; and
The new product results in a meaningful reduction in disease morbidity or mortality.
The modulated periods of market exclusivity are:
Orphan products addressing high unmet medical needs will benefit from market exclusivity of 10 years
Well-established use orphan products will benefit from 5 years of market exclusivity
All the other orphan products will benefit from 9 years of market exclusivity
Market exclusivity can be prolonged by 12 months for the supply of the product
Market exclusivity can be extended by an additional 12 months if an MA holder obtains approval for a different orphan condition, provided the approval is granted at least two years before the end of the exclusivity period. Such a prolongation may be granted twice if the new therapeutic indications are each time for different orphan conditions.
This contrasts with the current rules, where additional orphan conditions benefit from a separate orphan market exclusivity period.
The prolongation of market exclusivity, either for the supply of the product or approval of new therapeutic indications, is not available for well-established use products.
Effect of market exclusivity
The draft Regulation introduces major changes to the scope of market exclusivity for orphan medicines:
Where an MA holder holds more than one orphan MA for the same active substance, there will be a single exclusivity period starting from the date when the first orphan MA was granted - the so-called “global orphan MA” approach.
MA applications for a similar medicinal product (including generics and biosimilars) will be possible before the market exclusivity expires, i.e., “where the remainder of the duration of the market exclusivity is less than two years”.
Therefore, the de facto market exclusivity periods will be shortened because the MA for similar products can be granted immediately after the market exclusivity expires. Under the current rules, market exclusivity prevents not only the granting of MAs but also the acceptance of MA applications.
