EU/3/12/1094: Orphan designation for the treatment of achondroplasia

Achondroplasia represents the most common form of short-limb dwarfism, a condition where the bones in the arms and legs do not form properly and are shorter than normal. Patients with achondroplasia have a short stature, an enlarged head with a prominent forehead, bowed legs, ear problems, compression of the spinal cord, as well as short fingers, toes, lower legs and upper arms.

Achondroplasia is an inherited disease caused by a mutation (defect) in a gene called fibroblast growth-factor receptor 3 (FGFR3). Patients who have inherited the defective gene from both parents are the most severely affected and normally die around birth or a few months afterwards. In patients with only one defective FGFR3 gene, achondroplasia causes long-term disability and may result in a shorter life span because of its effects on the heart.

At the time of designation, achondroplasia affected approximately 0.42 in 10,000 people in the European Union (EU). This was equivalent to a total of around 21,000 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 509,000,000 (Eurostat 2013).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of achondroplasia. Patients were given supportive care, as well as surgery to extend limb length, to correct spinal compression or to correct bowed legs.

In patients with achondroplasia, the gene FGFR3 is permanently 'switched on', and this prevents the normal growth of bones, ultimately leading to bones that are shorter than normal. This medicine is expected to work by attaching to a receptor called natriuretic peptide receptor type B (NPR-B) on the surface of cells, which is thought to 'switch off' the activity of FGFR3. This is expected to stimulate the normal growth of bones, thereby improving the symptoms of the disease.

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, clinical trials with the medicine in patients with achondroplasia were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for achondroplasia 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 6 December 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.