EU/3/16/1753: Orphan designation for the treatment of leukocyte adhesion deficiency type I

Leukocyte adhesion deficiency type I is a disease caused by changes in the gene for a protein called CD18. This reduces the activity of the immune system (the body's natural defences) by preventing neutrophils (a type of white blood cell that fights infection) from reaching the site of an infection or injury. This results in repeated bacterial infections beginning with umbilical cord infections shortly after birth. Patients go on to suffer infections of the skin, digestive tract, lungs and airways and moist body surfaces such as the lining of the mouth.

Leukocyte adhesion deficiency type I is a debilitating and life-threating disease because the bacterial infections may be severe and patients may need continuous antibiotic treatment. The severe form of the disease usually leads to death in early childhood.

At the time of designation, leukocyte adhesion deficiency type I 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 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, no satisfactory methods were authorised in the EU for the treatment of leukocyte adhesion deficiency type I. Patients were given antibiotics to treat infections. Patients also received haematopoietic stem cell transplantation, a procedure where the patient's bone marrow is replaced by stem cells from a donor to form new bone marrow that produces healthy blood cells.

This medicine is made up of haematopoietic stem cells taken from the patient. Haematopoietic stem cells are cells that can develop into different types of blood cell. To make the medicine, the cells are modified in the laboratory by a virus that carries healthy copies of the CD18 gene into the cells. When these modified cells are given back to the patient, they are expected to develop into healthy white blood cells that can reach the sites of infection and fight it off.

The virus used in this medicine (lentivirus) is modified in order not to cause disease in humans.

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 leukocyte adhesion deficiency type I had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for leukocyte adhesion deficiency type I 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 September 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.