EU/3/16/1664: Orphan designation for the treatment of homocystinuria

Homocystinuria is an inherited disorder which causes a substance called homocysteine to accumulate in the blood and urine. Patients with homocystinuria usually lack a functioning cystathionine B-synthase, an enzyme that is responsible for breaking down homocysteine. When this enzyme does not work properly, excess homocysteine accumulates in the body which can be toxic at high levels. Symptoms of the disease usually appear in the first few days of life and long-term consequences include learning disabilities, brittle bones, problems with vision and blood disorders.

Homocystinuria is a long-term debilitating and life-threatening disease that leads to blood clots and problems with the heart and blood vessels, and is associated with poor overall survival.

At the time of designation, homocystinuria affected less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 10,000 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 513,700,000 (Eurostat 2016).

At the time of designation, betaine was authorised in the EU for the treatment of homocystinuria.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with homocystinuria because studies in experimental models suggested that the medicine used together with the authorised treatment betaine could lower further homocysteine levels. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is an enzyme replacement therapy that is expected to work by replacing the malfunctioning enzyme in homocystinuria, helping to break down homocysteine and stopping it from building up in the body.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with homocystinuria had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for homocystinuria. Orphan designation of the medicine had been granted in the United States for the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 April 2016 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.