EU/3/18/2118: Orphan designation for the treatment of Hutchinson-Gilford progeria

Hutchinson-Gilford progeria syndrome is a genetic condition in which features resembling aging appear in childhood.

Children born with Hutchinson-Gilford progeria syndrome 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 syndrome 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 syndrome 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 517,400,000 (Eurostat 2018).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of Hutchinson-Gilford progeria syndrome. 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 syndrome is caused by mutations (changes) in the LMNA gene, which produces lamin A, a protein that helps to keep cells of the body strong and stable. People with Hutchinson-Gilford progeria syndrome have abnormal lamin A, which causes damage to cells and leads to symptoms of aging early in life.

It is thought that lonafarnib may help prevent formation of abnormal lamin A thereby improving symptoms of the disease.

The effects of lonafarnib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with Hutchinson-Gilford progeria syndrome were ongoing.

At the time of submission, lonafarnib was not authorised anywhere in the EU for Hutchinson-Gilford progeria syndrome. Orphan designation of the medicine had been granted in the United States for Hutchinson-Gilford progeria syndrome.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 November 2018 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.