EU/3/12/1003: Orphan designation for the treatment of adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is an inherited disease, seen almost exclusively in males, that affects the brain, nerves and the adrenal glands (small glands located above the kidneys). ALD is caused by abnormalities in a gene called ABCD1 which is responsible for the production of a protein called ALDP (adrenoleukodystrophy protein). Patients with the disease lack ALDP which is needed to break down fatty substances in the body called very long chain fatty acids (VLCFA). Because patients with ALD cannot break these fatty substances down, they gradually build up in cells in the body, particularly in the brain, nerves and adrenal glands. In the brain and spinal cord, the build-up of VLCFA leads to inflammation and destruction of the protective sheath (myelin) that insulates and improves the way the nerves function. In the adrenal gland,s its build-up causes their dysfunction (adrenal insufficiency) and reduces their ability to produce hormones, such as cortisol. This leads to a wide range of symptoms, including behavioural problems, problems with vision, hearing and coordination, seizures (fits) and dementia.

ALD is life-threatening and long-term debilitating due to the progressive damage to the brain and nerves.

At the time of designation, ALD affected not more than 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 20,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 509,000,000 (Eurostat 2012).

At the time of application, there was no satisfactory treatment authorised in the EU for ALD. Haematopoietic (blood) stem-cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow) had been used in some patients. Corticosteroids were also used to treat the adrenal insufficiency

This medicine is made up of immature bone marrow cells that are taken from the patient. These cells are able to develop into different types of cells, including brain cells. To make this medicine, the cells are modified by a virus that contains a functional copy of the gene ABCD1 for the ALDP protein, so that this gene is carried into the cells. When these modified cells are transplanted back into the patient, they are expected to develop into healthy cells that produce the ALDP protein, which is lacking in patients with ALD. As a result, any accumulated VLCFA will be broken down and this will help to reduce the symptoms of the disease.

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

The effects of the medicine have been evaluated in experimental models.

At the time of submission, preliminary clinical trials with the medicine in patients with ALD had been conducted.

At the time of submission, the medicine was not authorised anywhere in the EU for ALD 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 12 April 2012 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.