EU/3/16/1773: Orphan designation for the treatment of cytomegalovirus infection in patients with impaired cell-mediated immunity

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 and only becomes active if the body's immunity, specifically its cell-mediated immunity, is weakened.

Cell-mediated immunity is a defence mechanism where specialised cells of the immune (defence) system called T lymphocytes or T cells directly neutralise viruses. In people with weakened cell-mediated immunity, such as transplant patients receiving immunosuppressant treatment (medicines that reduce the activity of the immune system), cytomegalovirus is not neutralised and causes severe infection.

Cytomegalovirus infection in patients with impaired cell-mediated immunity 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 in transplant patients.

At the time of designation, cytomegalovirus infection in patients with impaired cell-mediated immunity affected approximately 1.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 82,000 people¹, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

¹Disclaimer: For the purpose of the designation, the number of patients affected by 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 antiviral medicines were authorised in the EU for the treatment of cytomegalovirus disease in patients with impaired cell-mediated immunity (foscarnet, ganciclovir, valaciclovir and valganciclovir).

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for the treatment of cytomegalovirus infection in patients with impaired cell-mediated immunity. This is because early studies indicate that it may be effective in patients with cytomegalovirus infection not responding to existing antiviral medicines. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of cells of the immune system called T cells taken from a donor who had been previously infected with cytomegalovirus. The T cells are mixed with other cells that have a cytomegalovirus protein on their surface. As a result, the T cells learn to recognise cytomegalovirus as 'foreign'. The T cells are then grown to increase their numbers. When given to the patient, these T cells are expected to attack the cytomegalovirus in the patient and thereby help cure the infection.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with cytomegalovirus infection in patients with impaired cell-mediated immunity were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for cytomegalovirus infection in patients with impaired cell-mediated immunity 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 6 October 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.