The European Medicines Agency (EMA) recommended 17 drugs with orphan product designation for approval in 2014, the most ever in a single year.
This is much higher than the average of 6.75 per year between 2010 and 2013 and is a significant increase from 2013, when EMA recommended 11 products with orphan designation for approval.
Background: Orphan Designation
Orphan product designation was first introduced in the EU in 2000 under Regulation (EC) No 141/2000. The regulation established the procedure for orphan product designation, detailed incentives for products granted orphan designation and formed the Committee for Orphan Medicinal Products (COMP) which is charged with reviewing applications for the designation.
Since 2000, the European Commission adopted several guideline documents and communications clarifying issues related to the agency’s interpretation of the regulations, assessing similarity of medicinal products and reviewing market exclusivity.
EMA provides certain benefits and incentives to sponsors whose products qualify for orphan designation. In order to gain orphan designation in the EU, a medicine must satisfy several conditions.
- The medicine must treat, prevent or diagnose a life-threatening or chronically debilitating condition.
- The condition must affect fewer than 5 in 10,000 people in the EU. Alternatively, if a condition affects more than 5 in 10,000 people in the EU it may still be considered for orphan designation if it is “unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development.”
- Finally, for a treatment to qualify for orphan designation there must be no existing approved treatments for the indicated condition, or if there are, the product in question must offer significant improvements over the other options.
A Big Year for Orphans in the EU
Among the 17 orphan products recommended by EMA for approval are several firsts, including the first treatment for Duchenne muscular dystrophy, Translarna, and erythropoietic protoporphyria (Scenesse). Another product, Holoclar, which treats limbal stem cell deficiency, is the first ever treatment based on stem cells to be recommended for approval.
In addition to their orphan product designation, these three products also used special regulatory pathways to speed their assessments. Holoclar and Translarna were both given a conditional marketing authorization, while Scenesse was granted approval under exceptional circumstances.
Not all drugs recommended for approval were ultimately approved. Of the 17 orphan products recommended for approval, Vynfinit, along with its companion diagnostics Folcepri and Neocepri, were withdrawn by their sponsor before being authorized by the European Commission (EC) after preliminary data from an ongoing study was unable to show Vynfinit’s benefit to patients with ovarian cancer.
How Orphan Designation Works
There are two primary benefits given to sponsors of orphan products.
Sponsors of orphan products can receive scientific advice and protocol assistance from EMA. Scientific advice is a type of prospective (and not legally binding) advice where the agency can advise a company on the “appropriate tests and studies” to conduct during a medicine’s development. Protocol assistance is given to sponsors of orphan products to answer questions related to demonstrating if their product offers significant benefit over other available treatments. Protocol assistance can also be given to assess similarity to other orphan products with the same indication.
The other primary benefit gained from orphan product designation is market exclusivity for a period of 10 years. To receive market exclusivity, sponsors are required to submit an application supporting the maintenance of their product’s orphan designation. Market exclusivity can be given for each specific orphan designation a product carries. This means that a product with multiple orphan designations for different conditions could have separate market exclusivity for the different conditions. If a sponsor complies with a paediatric investigation plan (PIP) the period of market exclusivity for an orphan product can be increased by two years.
If, at the end of an orphan product’s fifth year on the market, the product can be shown to be sufficiently profitable, the period of market exclusivity can be reduced to six years.
Additionally, products with orphan designation can receive fee reductions for certain activities or services, with the amount of the reduction varying based on the product’s indication and sponsor’s status as a micro, small or medium-sized enterprise (SME).
Trends in the Industry
EMA wasn’t the only agency to have a record year for orphan drugs. The US Food and Drug Administration (FDA) approved 15 treatments for rare diseases in 2014 (37% of all drugs approved), two more than its previous record of 13 in 2012. The uptick in products approved to treat rare diseases is part of a growing trend in the pharmaceuticals industry to target rare diseases where incentives from orphan drug initiatives and high potential treatment prices offset the effect of a smaller patient population.
EMA Press Release