EU/3/07/519: Orphan designation for the prevention of cytomegalovirus disease in patients with impaired cell-mediated immunity

Cytomegalovirus (CMV) is a virus that infects many people worldwide. In the majority of cases the virus is latent (inactive) and causes neither disease nor any symptoms of any kind in man. Usually, the virus is only activated in patients who, for some reason, have a weaker immune system (natural defence system against pathogens such as bacteria and virus) than normal. That is called “impaired immunity”. Impaired immunity is seen, for example, in organ transplanted patients who are receiving the necessary medicines to suppress the immune system and in patients with acquired immunodeficiency disease, e.g. due to human immunodeficiency virus (HIV) and who subsequently develop acquired immunodeficiency syndrome (AIDS). The risk of activation of latent CMV is particularly high if the cellular component of the immune system is weakened (the “cell mediated immunity”). CMV disease can affect several organs in the body, such as the eyes, lungs and the gastrointestinal tract (the stomach and intestines) and cause organ failure. CMV disease is chronically debilitating and life-threatening.

At the time of designation, the number of patients with impaired cell mediated immunity deemed at risk of cytomegalovirus (CMV) disease was estimated to be less than 4 people in 10,000 in the European Union (EU) *. This is equivalent to a total of fewer than 200,000 people, which is below the threshold 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 498,000,000 (Eurostat 2006).

Several medicinal products were authorised for the prevention of CMV disease in the Community at the time of orphan drug application. Current methods of prevention aim to decrease the production of virus particles (virions) by inhibiting (blocking) a viral enzyme (a protein that speeds up the conversion of certain substances into other substances) called CMV DNA polymerase. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that maribavir might be of potential significant benefit for the prevention of cytomegalovirus (CMV) disease in patients with impaired cell mediated immunity deemed at risk, mainly because it has a new mechanism of action, may be used in combination with other treatments and may potentially work in patients where other methods of prevention are unsuccessful. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Maribavir is designed to bind to and inhibit (block) a viral enzyme called UL97 that is necessary for the virus for many processes. According to the sponsor, maribavir will inhibit this enzyme and thus prevent viral activation from latency in immunocompromised patients.

The effects of maribavir were evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in patients with impaired cell mediated immunity were ongoing.

Maribavir was not authorised anywhere worldwide for the prevention of cytomegalovirus (CMV) disease in patients with impaired cell mediated immunity deemed at risk, at the time of submission. Orphan designation of maribavir was granted in the United States for prevention of cytomegalovirus viremia and disease in the population at risk.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 8 November 2007 a positive opinion recommending the grant of the above-mentioned 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 European Union) 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.