EU/3/12/1042

On 9 August 2012, orphan designation (EU/3/12/1042) was granted by the European Commission to Astellas Pharma Europe B.V., the Netherlands, for covalently closed DNA plasmids coding for cytomegalovirus phosphoprotein 65 and glycoprotein B genes for the prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity deemed at risk.

What is cytomegalovirus disease?

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 infection of the lungs, liver and digestive tract, as well as reduced graft survival in transplanted patients.

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients with impaired cell-mediated immunity at risk of cytomegalovirus disease was estimated to be less than 3 people in 10,000 in the European Union (EU)*. This is equivalent to a total of fewer than 152,000 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. This represents a population of 506,300,000 (Eurostat 2011).

What methods of prevention are available?

At the time of orphan designation, several antiviral medicines (aciclovir, ganciclovir, valaciclovir and valganciclovir) were approved in the EU for the prevention of cytomegalovirus disease in transplant recipients. 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 might be of significant benefit for patients at risk of cytomegalovirus disease because it works in a different way to existing treatments, and is expected to stimulate both cell-mediated immunity (which involves cells directly attacking the virus) and humoral immunity (which involves the use of specialised proteins called antibodies to attack the virus). In addition, it may reduce the need for antiviral treatment which can have several side effects. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine contains the genes (DNA) responsible for making two proteins of the CMV virus (phosphoprotein 65 and glycoprotein B). When given to the patient, the genes are expected to produce the two proteins, which are in turn expected to stimulate an immune response against the cytomegalovirus. The immune system is then expected to be able to produce a more effective response when it is exposed to the virus again.

The two proteins in the medicine have been chosen because they are expected to be able to stimulate cell-mediated immunity and humoral immunity.

What is the stage of development of this medicine?

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 transplant recipients were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for prevention of cytomegalovirus disease. Orphan designation of the medicine had been granted in the United States of America for prevention of cytomegalovirus disease and associated complications.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 July 2012 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.