EU/3/12/957: Orphan designation for the treatment of X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is a group of inherited diseases in which certain immune cells called phagocytes are unable to produce the substances needed to kill microbes. In X-linked CGD, this is caused by a defect in a gene on the X chromosome. This gene is responsible for the production of a protein called gp91(phox), which is lacking in these patients.

In CGD, the phagocytes are still able to engulf the microbes but, as they cannot kill them, the patients suffer repeated infections, and clumps of white blood cells called granulomas appear in various organs.

X-linked CGD is a long-term and life-threatening disease due to severe infections and the formation of granulomas in internal organs.

At the time of designation, X-linked CGD affected less than 0.02 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 1,000 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. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, the main treatments for X-linked CGD included lifelong use of antibiotics and anti-fungal agents to prevent infections from occurring, interferon gamma to stimulate the immune system and aggressive early treatment of infections.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with X-linked CGD because it works in a different way to existing treatments by directly targeting the genetic defect that causes the condition, which could improve the outcome of patients. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made up of immature haematopoietic (blood) cells that are taken from the patient. These cells are able to develop into different types of blood cell. To make this medicine, the cells are modified by a virus that contains the gene for the gp91(phox) protein, so that this gene is carried into the cells. When these modified cells are transplanted back into the patient, they are expected to populate the bone marrow and produce healthy phagocytes with the gp91(phox) protein, which is lacking in patients with X-linked CGD. The type of 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 autologous haematopoietic cells genetically modified with a lentiviral vector containing the human gp91(phox) in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with X-linked CGD had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for X-linked CGD 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 7 December 2011 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.