EU/3/05/348: Orphan designation for the prevention of Japanese encephalitis

Japanese encephalitis is a disease caused by the Japanese encephalitis SA14-4-2 virus, which causes an inflammation of the membranes around the brain (encephalitis) in humans. Certain types of mosquitoes carry the virus from animals (mostly pigs) to humans. Japanese encephalitis virus cannot be transmitted from person-to-person even through mosquito bites. Japanese encephalitis is a leading cause of viral encephalitis in Asia. It occurs from the islands of the Western Pacific in the east to the Pakistani border in the west, and from Korea in the north to Papua New Guinea in the south. Japanese encephalitis distribution is known to be linked to irrigated rice production combined with pig rearing. Most Japanese encephalitis virus infections are mild (fever and headache) or without apparent symptoms, but approximately 1 in 200 infections results in severe disease and sometimes death. The disease is characterized by rapid onset of high fever, headache and other more serious effects due to the inflammation of the membranes around the brain, that in some patients could lead to long-term or permanent disability even after recovery.
Japanese encephalitis might occur among travellers to Eastern and South Eastern Asia and can be chronically debilitating and life-threatening.

At the time of designation, the number of patients at risk of Japanese encephalitis 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 138,000 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 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

Preventive measures against infection are the standard anti-mosquito precautions. There are at present no products authorised in the EU for prevention of the condition but there is a vaccine used for Japanese encephalitis, which can be made available upon request.

Purified inactivated Japanese encephalitis SA-14-4-2 virus vaccine is a vaccine made of a specific killed Japanese encephalitis virus, called SA-14-4-2. Once injected in the body, it can stimulate the body's defense system (immune system), aimed at building an immune response as a protection against a potential infection of the similar (active) virus.

At the time of submission of the application for orphan designation, clinical trials in subjects at risk of Japanese encephalitis were ongoing.
Purified inactivated Japanese encephalitis SA-14-4-2 virus vaccine was not authorised anywhere worldwide for the prevention of Japanese encephalitis or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 7 December 2005 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 Community) 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.