EU/3/11/849: Orphan designation for the prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity

Cytomegalovirus is a common virus that can cause 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 remains in the body in a 'latent' (inactive) state and only becomes active again if the body's immunity, specifically its cell-mediated immunity, is weakened.

Cell-mediated immunity is a defence mechanism where specialised cells called T-lymphocytes directly neutralise viruses. In people with weakened cell-mediated immunity, such as patients with HIV infection or transplant patients receiving immunosuppressant treatment (medicines that reduce the activity of the immune system), cytomegalovirus can become active again and, this time, cause severe infection.

Cytomegalovirus disease 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 lungs, liver and digestive tract, as well as reduced graft survival in transplanted patients.

At the time of designation, the number of patients with impaired cell-mediated immunity at risk of cytomegalovirus disease was estimated to be approximately 3.1 people in 10,000 in the European Union (EU)*. This is equivalent to a total of around 157,000 people, which 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).

*Disclaimer: 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

At the time of designation, several antiviral medicines were authorised in the EU for the prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity deemed at risk (ganciclovir, valganciclovir and valaciclovir). Patients at risk were also closely monitored to detect signs of cytomegalovirus infection as early as possible.

The sponsor has provided sufficient information to show that the medicine '(S)-{8-fluoro-2-2[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)-phenyl]-3, 4-dihydro-4-quinazolinyl} acetic acid' might be of significant benefit for patients with impaired cell-mediated immunity at risk of cytomegalovirus disease because it has a different mechanism of action to current treatments, which may bring improved effectiveness against strains of cytomegalovirus resistant to existing antiviral medicines. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

During replication, cytomegaloviruses have their DNA packaged into small protein shells. This medicine is thought to block the action of an enzyme in the virus called 'terminase', which is involved in cleaving the DNA strands to fit within the shells. By blocking the enzyme, the medicine is expected to prevent the DNA in the virus from reaching maturity, thereby killing the virus.

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 impaired cell-mediated immunity at risk of cytomegalovirus disease were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity deemed at risk 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 12 January 2011 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.