An In-Depth Look at the European Medicines Agency’s Orphan Drug Designation Post-Brexit


On February 3, 2020, twenty-seven newly installed flags of the European Union stood in the gleaming lobby of the new European Medicines Agency (EMA) headquarters in Amsterdam.

The Charcot-Marie-Tooth News chronicled the post-Brexit relocation from their London office. A new era had begun.

The EMA’s Mission

According to the EMA’s director Guido Rasi, with their move from London complete, they can now focus on medical therapies for the twenty-five million patients with rare diseases who live in the EU.

There are 780 people employed at the agency with the staff coming primarily from Spain, France, and Italy.

The EMA’s COMP, established in the year 2000, is the Committee for Orphan Medicinal Products. Its Chairman is Dr. Violeta Stoyanova.

Qualifications for Orphan Drug Designation

In order to become eligible for orphan drug designation, the medicine must be developed with the intention of preventing, diagnosing or treating a chronically debilitating or life-threatening disease.

Two other requirements are that the number of patients with the rare disease must not exceed five cases out of a total of 10,000 patients in the EU’s twenty-seven member states or it is evident that the therapy would not generate sufficient revenue towards a return on investment.

An Incentive for Development

In 2000, the same year that COMP was established, the European Commission gave its approval for legislation to incentivize the development of rare disease medications. This was well-received because the rare disease market is usually not a high priority with pharma companies due to its low returns.

The EU also has the distinction of being home to several large markets for orphan drugs which include Italy, Germany, the Netherlands, and France.

Not every drug makes it to authorization application status. But the ones that do undergo strict evaluation by the EMA’s Committee for Medicinal Products for Human Use. Currently, there are one hundred forty orphan medicines that have received authorization in the EU.

Anyone May Apply

Chairman Stoyanova explained that EU legislation allows anyone to apply for orphan designation at any time during the drug’s development.

This allows scientists, for example, to go to the committee with data from one of their early experiments. Using animal models, scientists could submit data for some drugs that they intend to develop for a specific rare disease.

Another example would be a drug that is further advanced in development and the scientists are able to show clinical data from several patients.

When data is judged to be sufficient along with the requisite criteria being satisfied, the applicant receives the  designation. It is then eligible for incentives.

Pre-marketing Incentives

Dr. Stoyanova said that the ten-year market exclusivity is probably the most attractive incentive in the program. As long as the therapy remains in orphan status, no other similar product can enter the market.

However, a reassessment may be triggered by one of the member states at the five-year mark.

Other incentives are research subsidies, tax incentives for research investment, and exemptions from EMA user fees.

About the Requirements

Applicants must show through a pilot project or experiment that the concept is feasible and medically worthy of approval.

With respect to proof by way of an experiment, if the drug is being considered to treat cystic fibrosis (CF) for example, the experiments must be conducted on patients or animals with CF.

A criteria for drugs that will be reaching the market is to establish that the product would be the first drug approved for a specific disease.

On the other hand, if there are products or therapies already in use for a specific disease, the newly submitted orphan drug must be superior or at a minimum must show substantial benefits for the patient.

Dr. Stoyanova said that other scientific grants may be available that are designed to encourage new therapies.

Therapies Approved in 2018

The following therapies that received EMA approval in 2018:

Lamzede (velmanase alfa): to treat alpha-mannosidosis

Mepsevii (vestronidase alfa): for treating mucopolysaccharidosis type VII

Namuscla (mexiletine hcl): treats muscle stiffness in adults with a form of myotonic disorder

Luxturna: gene therapy that treats retinal dystrophy

Additional COMP Members

COMP includes patient delegates representing a Dutch network consisting of people with rare cancers.

Delegates from the Italian Thalassemia Foundation are among the attendees along with university professors and clinicians who the EU appoints to provide guidance where needed.  

COMP meets for three days every month at the EMA’s headquarters in Amsterdam for discussions on pending applications.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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