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Orphan designation

On 10 October 2012, orphan designation (EU/3/12/1051) was granted by the European Commission to Alphacore Pharma Limited, United Kingdom, for recombinant human lecithin cholesterol acyltransferase for the treatment of lecithin-cholesterol-acyltransferase deficiency.

The sponsorship was transferred to AstraZeneca UK Limited, United Kingdom, in February 2016.

What is lecithin-cholesterol-acyltransferase deficiency?

Lecithin-cholesterol-acyltransferase deficiency is an inherited disease caused by abnormalities in the gene responsible for the production of the lecithin-cholesterol-acyltransferase (LCAT) enzyme. LCAT is key to transporting cholesterol from tissues into the liver for excretion into the bile. A deficiency of LCAT results in cholesterol and other types of fats building up in tissues, mostly in the cornea (the transparent layer in front of the eye), red blood cells and kidneys. Symptoms of the disease include corneal opacity (clouding of the cornea), haemolytic anaemia (low red blood cell counts caused by the cells being destroyed too soon) and kidney disease which can lead to kidney failure.

LCAT deficiency is chronically debilitating due to corneal opacity that affects vision and the development of anaemia. It is also life-threatening due to severe kidney damage, which may lead to kidney failure.

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

At the time of designation, LCAT deficiency affected approximately 0.001 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 50 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of orphan designation, no satisfactory treatments were authorised in the EU for this condition and only limited symptomatic treatment was available.

How is this medicine expected to work?

This medicine is made of the LCAT enzyme produced by a method known as ‘recombinant DNA technology’: it is made by cells that have received a gene (DNA) which makes them able to produce LCAT. This medicine is expected to work by replacing the missing enzyme, which can then modify cholesterol from tissues so that it can be transported to the liver and excreted into the bile. This is expected to reduce the deposit of cholesterol in tissues, thus improving the symptoms of the disease.

What is the stage of development of this medicine?

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 of the application for orphan designation, no clinical trials with the medicine in patients with LCAT deficiency had been started.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 September 2012 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.

Key facts

Product details for <p>Recombinant human lecithin cholesterol acyltransferase</p>
Active substanceRecombinant human lecithin cholesterol acyltransferase
Medicine Name
Disease/conditionTreatment of lecithin-cholesterol-acyltransferase deficiency
Date of decision10/10/2012
Orphan decision numberEU/3/12/1051

Review of designation

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

Sponsor’s contact details:

UK Limited
Charter Way
Macclesfield AstraZeneca
Cheshire East SK10 2NA
United Kingdom
Tel. +44 (0)1625 516 338
Fax +44 (0)1625 517 085

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.