EU/3/16/1644: Orphan designation for the prevention of cytomegalovirus disease

Cytomegalovirus is a common virus that usually only causes mild infection such as a sore throat. Most people get infected at some stage during their lifetime but are very often unaware of it. After infection, the virus usually remains in the body in a 'latent' (inactive) state.

However, cytomegalovirus, which may have been latent, can become active again and cause severe infection if the immune system (the body's natural defences) is weakened, such as in people who receive a stem cell transplant.

Cytomegalovirus disease is long-term debilitating and life-threatening because of the complications it causes, such as inflammation of the eyes, lungs, liver and digestive tract, as well as reduced survival of transplanted organs or tissues.

At the time of designation, the number of patients at risk of cytomegalovirus disease was estimated to be approximately 3.2 people in 10,000 per year in the European Union (EU). This was equivalent to a total of around 164,000 people per year*, and is below the ceiling for orphan designation. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients at risk of developing the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

At the time of designation, several medicines were authorised in the EU for the prevention of cytomegalovirus disease (human cytomegalovirus immunoglobulin, ganciclovir, valaciclovir and valganciclovir).

The sponsor has provided sufficient information to show that brincidofovir might be of significant benefit for patients at risk of cytomegalovirus disease because data from the published literature show that this medicine may reduce the occurrence of cytomegalovirus disease in patients undergoing stem-cell transplantation. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Brincidofovir is an antiviral medicine that belongs to the class 'nucleotide analogues'. It blocks the activity of enzymes called 'DNA polymerases' in cytomegalovirus, which the virus uses to produce DNA. When the virus cannot produce DNA, it cannot reproduce, slowing down the spread of infection.

The effects of brincidofovir have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with brincidofovir in patients at risk of cytomegalovirus disease were ongoing.

At the time of submission, brincidofovir was not authorised anywhere in the EU for prevention of cytomegalovirus disease or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 March 2016 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.