EU/3/02/096: Orphan designation for the treatment of alkaptonuria

Alkaptonuria is a genetic disease, where a deficiency in an enzyme, the homogentisic acid oxidase, leads to the accumulation of homogentisic acid (HGA) and its metabolites, which have deleterious effects on cartilage. The condition is sometimes revealed in infants by a bluish colour of eye conjunctiva, or dark colouring of urine in diapers. The most common symptoms occur during childhood or early adulthood. They include joint pain such as spinal pain, limited joint mobility, and joint deterioration of mainly the hips, knees and shoulders in the third or fourth decade of life. The condition may be seriously disabling and lead to the need for early surgical joint replacement.

At the time of designation, alkaptonuria affected approximately 0.02 - 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of around 760 – 1,900 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.
At the time of designation, this represented a population of 380,600,000 (Eurostat 2002).

At the time of submission of the application for orphan designation, no satisfactory method had been authorised in the European Union for treatment of the condition. Joint damage has led to the need for surgical replacement such as hip replacement at an early age.

Nitisinone interrupts the formation of HGA, by inhibiting the enzyme that produces HGA.

A limited pharmacokinetic study has been performed.

At the time of submission of the application for orphan designation, further clinical trials in patients with alkaptonuria had not been initiated.

Nitisinone had not been marketed anywhere worldwide for alkaptonuria or designated as an orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 January 2002 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.