NATIONAL HARBOR, Maryland — The top official for rare disease therapies at the European Medicines Agency (EMA) said her office is seeing a steadily increasing number of applications for new therapies despite the disruptions caused by the COVID-19 pandemic.

Violeta Stoyanova-Beninska, MD, PhD, chairs the Committee for Orphan Medicinal Products (COMP) at EMA, the European counterpart to the US Food and Drug Administration (FDA). 

The Amsterdam-based EMA, which relocated to the Dutch capital from London in 2020 following the UK’s departure from the EU, operates on an annual budget of €385.9 million (about $455 million). It employs 780 people, with the largest numbers of staffers coming from Italy, Spain, and France.

Dr. Stoyanova gave a 20-minute video presentation on August 26, 2021, for the World Orphan Drug Congress USA 2021. In it, she explained how her COMP — 1 of 7 committees at EMA — was established in 2000 to evaluate applications for orphan designation of medicines for rare diseases.

To qualify for orphan designation, a medicine must intend to treat, prevent, or diagnose a disease that is life-threatening or chronically debilitating. In addition, the prevalence of the condition among the EU’s 27 member states cannot exceed 5 in 10,000, or about 250,000 cases — or it must be unlikely that sales of the medicine would generate sufficient returns to justify the investment needed to develop it.

Violeta Stoyanova-Beninska, MD, PhD, chairs the Committee on Orphan Medicinal Products at the European Medicines Agency (EMA). Credit: EMA

Among the incentives EMA offers pharmaceutical companies are fee reductions and exemptions, product development assistance, and 10-year market exclusivity (12 years for pediatric drugs)

“Market exclusivity does not mean that one product blocks anything else which is in development for the same disease,” Dr. Stoyanova said. “Products with a different mechanism of action, structure, or effect on the disease can be approved if they have shown that they have a positive benefit-risk [ratio] and show significant benefits for those patients.” 

Dr. Stoyanova, originally from Bulgaria, has chaired COMP since September 2018, when she was elected to a 3-year term. COMP consists of delegates nominated by each of the EU’s 27 member states, plus 2 members nominated by Iceland and Norway, 3 patient representatives, and 1 observer from the Eurordis umbrella organization of patient groups.

Flags of the EU’s 27 member states at EMA headquarters, Amsterdam. Credit: EMA

At the moment, Dr. Stoyanova said, the EMA has authorized nearly 3000 orphan designations for 550 conditions, with just over 200 orphan products currently on the EU market. 

“Some products still have orphan status, while some have lost it already, either because market exclusivity has expired, or it has been withdrawn,” she said, adding that the number of applications has been growing steadily, with drugs for oncology accounting for 32% of all such applications; the next 2 largest areas are therapies for metabolic diseases and those of the central nervous system. 

“In 2020, there were 149 applications, including 21 that address new conditions. This is a very positive signal for the committee,” she said. “We would like to see these numbers rise, meaning that drug development is focusing on new disease areas where there is a high unmet need.”


Regulation of orphan medicinal products in EU: current and future challenges. Presented at: World Orphan Drug Congress USA 2021: August 25, 2021; National Harbor, MD.