EU/3/10/748: Orphan designation for the treatment of Hutchinson-Gilford progeria

Hutchinson-Gilford progeria is a severe, genetic condition in which features resembling aging appear in childhood. Children born with Hutchinson-Gilford progeria live for around 13 years. They appear healthy at birth, but in the first few years of life they develop symptoms such as limited growth, a distinctive appearance with a small face and a pinched nose, loss of hair and body fat, prominent scalp veins, crowded teeth, small and fragile bones, and stiffness of joints. Later, the condition causes wrinkled skin and problems with the heart.

Hutchinson-Gilford progeria is a severe and life-threatening condition particularly because of the problems with the heart, which lead to premature death.

At the time of designation, Hutchinson-Gilford progeria affected less than 0.05 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 3,000 people, and is below the threshold 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 506,500,000 (Eurostat 2010).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of Hutchinson-Gilford progeria. Patients received supportive treatment to help them and their families to cope with the symptoms of the condition. This included psychological support, painkillers, nutritional supplements, physical aids, sealing of the teeth and use of wigs.

Hutchinson-Gilford progeria is caused by abnormalities in the LMNA gene, which is needed to produce lamina A, a protein in the nucleus of cells that helps in producing and repairing genetic material. Children with Hutchinson-Gilford progeria have an abnormal form of this protein, which disrupts the normal functioning of the nucleus, leading to symptoms of aging.

The two active substances in this medicine, pravastatin and zoledronic acid, are already authorised in the EU on their own for the treatment of high blood cholesterol and for the prevention of bone fractures. In Hutchinson-Gilford progeria, they are expected to work together by reducing the production of the abnormal protein. This is expected to restore the normal functioning of the nucleus, relieving the symptoms of Hutchinson-Gilford progeria.

The effects of pravastatin / zoledronic acid have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with pravastatin / zoledronic acid in patients with Hutchinson-Gilford progeria were ongoing.

At the time of submission, pravastatin / zoledronic acid was not authorised anywhere in the EU for Hutchinson-Gilford progeria 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 3 March 2010 recommending the granting of this designation.

• the seriousness of the condition,
• the existence of alternative methods of diagnosis, prevention or treatment and
• 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.