The marriage between molecular biology and in silico technologies has driven medical innovation at an unprecedented rate in recent years.

Notably, artificial intelligence is assisting the discovery and development of treatments for complex diseases. AI-based research requires the interrogation of vast datasets to identify biological features (or 'biomarkers') that suggest certain drugs can be used for particular indications and/or subsets of patients within a particular disease group, and working out what those drugs are. This form of medicine is often referred to as personalised or targeted medicine, because it can reach smaller groups of people with rarer conditions than has previously been the case.

For research and development companies working in this area, however, a dilemma arises: as drugs target smaller populations of people, how can sufficient returns be obtained to make the investment worthwhile? Let's look at one possibility the legislator has provided in response to this dilemma: orphan drug protection under Regulation 141/2000 in the EU (and as reproduced in UK law after 31 December 2020).

10 years market exclusivity

Orphan drug protection is a stand-alone regime of market exclusivity separate from patent rights and the 8+2+1 regime of exclusivity for regulatory data. It's designed to encourage companies to develop new drugs – and to carry out research on existing drugs – to treat rare diseases where the likely revenues available don't justify the research required.

Among other incentives for the development of orphan drugs is a 10-year market exclusivity period for the indication in question, following the grant of a marketing authorisation for the product.

Qualifying for orphan status

For a product to be classed as an orphan medicine, it must be intended for the diagnosis, prevention or treatment of either: 

• a life-threatening or chronically debilitating condition, affecting no more than five in 10,000 people in the EU or UK at the time of submission of the application for orphan designation, or
• a life-threatening, seriously debilitating or serious and chronic condition that, without incentives, it would be unlikely that the revenue after marketing of the medicinal product would cover the investment in its development.

There must be either no satisfactory method of diagnosis, prevention or treatment of the condition already existing, or, if there is, the new medicine must be of "significant benefit" to those affected by the condition.

Several medical or other considerations could show that the medicinal product is of significant benefit, even in circumstances where the active ingredient is the same. Particular benefits for a sub-sample of the population can provide a significant benefit and where there are serious and documented difficulties with the formulation or route of administration of an authorised medicinal product, a more convenient formulation or route may be considered a significant benefit. 

An orphan drug designation can therefore be obtained for a line extension of an existing orphan drug, providing the qualifying significant benefit can be demonstrated. 

Exclusivity against similar medicinal products

During the exclusivity period, no "similar medicinal product" to that drug can be placed on the market for the same therapeutic indication, unless the consent of the holder of the marketing authorisation of the original orphan drug is given, they are unable to supply sufficient quantities, or the new drug is "clinically superior".

Consequently, the holder of the marketing authorisation can prevent similar medicinal products from third parties entering the market. It is, however, in the interests of patients suffering from a rare disease to have access to a similar medicinal product giving them a significant benefit compared to a previously authorised orphan product.

As such, the fact that an orphan medicinal product enjoys the 10-year period of market exclusivity does not preclude a second, similar product from a third party being granted its own orphan drug designation and market exclusivity, even if it contains the same active ingredient. However, this similar product must also fulfil the requirements of significant benefit and be clinically superior (although the legislation and case law doesn't yet clearly define the difference between these concepts).

A powerful incentive for targeted treatments

The exclusivity period available for orphan drugs is therefore a powerful right to exclude rival products from the market, regardless of patent protection. As a result, there can be a race between manufacturers of rival medicinal products to obtain an orphan drug designation where the product qualifies.

This exclusivity is an incentive for drugs companies to invest in treatments targeted at diseases affecting small percentages of the population. As the advance of technology enables the increasing development of such treatments, orphan drug protection will become all the more important.

Find out more

If you'd like to discuss any of the issues raised in this article, please contact a member of our Life Sciences and Healthcare team.

Paul England is the co-author (with Simon Cohen) of A User's Guide to Intellectual Property in the Life Sciences, coming soon from Bloomsbury Professional.