EU/3/16/1820

Antiphospholipid syndrome (APS) is a clotting disorder in which patients are at greater risk of developing conditions such as deep vein thrombosis (a blood clot that usually develops in the leg) and arterial thrombosis (a clot in an artery), which can cause a stroke or heart attack. In women, APS is a known cause of recurring miscarriages because of blood clots in vessels supplying the baby.

APS is caused by the body's own immune (defence) system producing antibodies (known as antiphospholipid antibodies), which are thought to interfere with the clotting process and make the blood more likely to clot.

APS is a long-term debilitating and life-threatening disease because of the risk of heart attack, stroke and miscarriages.

At the time of designation, APS affected less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 103,000 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, there were no treatments authorised in the EU for antiphospholipid syndrome. Anticoagulants (e.g. warfarin) and platelet aggregation inhibitors (e.g. heparin) were used to prevent blood clots.

Hydroxychloroquine is expected to work in APS by stopping platelets clumping together, reducing production of antiphospholipid antibodies and lowering cholesterol levels. Together, these effects are expected to reduce the risk of blood clots.

The effects of hydroxychloroquine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with hydroxychloroquine in patients with APS were ongoing.

At the time of submission, hydroxychloroquine was authorised in the EU for various immune system conditions including rheumatoid arthritis.

At the time of submission, hydroxychloroquine was not authorised anywhere in the EU for APS or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 December 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.