EU/3/14/1284

Invasive aspergillosis is an infection caused by species of fungi known as Aspergillus. These fungi are very widely present in the air, but normally do not cause disease. In some people, usually when the immune system (the body's natural defences) is weakened, the fungus can attack and invade through the lungs and spread throughout the body via the bloodstream, damaging other organs and tissues including the heart, kidney, liver, brain, and bones.

Invasive aspergillosis is a life-threatening disease that can be fatal due to damage to the lungs and other organs.

At the time of designation, invasive aspergillosis affected less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 102,000 people*, 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).

*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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

At the time of designation, several medicines were authorised in the EU for the treatment of invasive aspergillosis, including voriconazole, posaconazole and amphotericin B.

The sponsor has provided sufficient information to show that isavuconazonium sulfate might be of significant benefit for patients with invasive aspergillosis because clinical studies have shown that it is as effective as authorised treatments but may have an improved safety profile, particularly with respect to effects on the liver. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Isavuconazonium sulfate is a product that belongs to the 'triazole' class of antifungal medicines. Once in the body, it is converted into its active form, isavuconazole, which is thought to work by blocking the actions of enzymes that are involved in making ergosterol, an important component of fungal cell membranes. Without a functional cell membrane, the Aspergillus fungus is expected to die or prevented from spreading.

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 isavuconazonium sulfate in patients with invasive aspergillosis were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for invasive aspergillosis. Orphan designation of isavuconazonium sulfate had been granted in the United States for treatment of this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 14 May 2014 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.