EU/3/14/1375: Orphan designation for the treatment of xeroderma pigmentosum

Xeroderma pigmentosum is an inherited skin disorder in which patients lack the ability to repair DNA damage caused by ultraviolet light.

Exposure to ultraviolet light and to toxic molecules formed inside the cells containing oxygen (reactive oxygen species or ROS) causes damage to DNA in the skin cells, but most people can repair the damage through a process known as 'nucleotide excision repair'. However, patients with xeroderma pigmentosum lack the enzymes required for excision repair and suffer significant skin damage when exposed to sunlight. Even a small amount of exposure can cause severe symptoms and these patients are at a very high risk of skin cancer.

Xeroderma pigmentosum is a long-term debilitating disease due to limitations in daytime activities and damage to the nervous system. It is also life threatening because patients are many times more likely than other people to get skin cancer.

At the time of designation, xeroderma pigmentosum affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

At the time of orphan designation, there were no satisfactory methods of treatment for patients with xeroderma pigmentosum.

Patients with xeroderma pigmentosum have a mutation (defect) in one of the genes (known as XPC) needed to make the enzymes for nucleotide excision repair that prevents the enzymes being produced. Studies in patients with a mutation in one of these genes have shown that an enzyme called NADPH oxidase-1, or NOX1, is then activated which leads to the production of ROS that in turn can lead to cancer.

This medicine is expected to block NOX-1 thereby reducing the amount of ROS produced which could potentially benefit patients with xeroderma pigmentosum, particularly in reducing the occurrence of skin cancer.

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 of the application for orphan designation, no clinical trials with the medicine in patients with xeroderma pigmentosum had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for xeroderma pigmentosum 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 9 October 2014 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.