EU/3/14/1315

On 22 August 2014, orphan designation (EU/3/14/1315) was granted by the European Commission to Cerenis Therapeutics Holding SA, France, for recombinant human apolipoprotein A-I in a complex with phospholipids for the treatment of apolipoprotein A-I deficiency.

What is apolipoprotein A-I deficiency?

Apolipoprotein A-I is a substance found in fatty particles in the blood called high-density lipoprotein (HDL). The cholesterol removed from cells normally attaches to these fatty particles and is commonly referred to as HDL or ‘good’ cholesterol. These particles are then transported to the liver where they can be broken down and the cholesterol removed from the body.

In patients with apolipoprotein A-I deficiency, mutations (defects) in the gene responsible for producing apoliprotein A-I result in low levels or the absence of this substance. This results in very low levels of HDL particles in the blood and in damaging build-up of cholesterol in blood vessels, liver, skin, nerves and eye.

Apolipoprotein A-I deficiency is a long-term debilitating and life-threatening condition due in particular to the cholesterol deposits in the arteries (atherosclerosis).

What is the estimated number of patients affected by the condition?

At the time of designation, the condition affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 500 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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).

What treatments are available?

No satisfactory methods of treatment were authorised in the EU for apolipoprotein A-I deficiency at the time of designation. Patients were usually managed with measures such as a low-fat diet and medicines to lower lipids (fats) in the blood.

How is this medicine expected to work?

The medicine contains replacement HDL-like particles containing apolipoprotein A-I in a form that absorbs cholesterol very efficiently. This temporarily restores the normal processes for removing excess cholesterol from the body by facilitating the loss of cholesterol from the cells, particularly in the walls of blood vessels.

The apolipoprotein A-I in this medicine is made by a method known as ‘recombinant DNA technology’: it is made by cells that have received a gene (DNA) that makes them able to produce the apolipoprotein.

What is the stage of development of this medicine?

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 this medicine in patients with apolipoprotein A-I deficiency were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for apolipoprotein A-I deficiency 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 10 July 2014 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.