EU/3/18/2101: Orphan designation for the treatment of leptin receptor deficiency

Leptin receptor deficiency is an inherited disease that causes severe obesity. Patients are born at normal weight but they are constantly hungry and quickly put on weight.

The disease is caused by mutations (changes) in the gene responsible for the production of the ‘leptin receptor’, the target for the hormone leptin. Normally when leptin attaches to the leptin receptor on nerve cells in the brain it stimulates signals to other nerves that make the body feel full and control feelings of hunger. In patients with the condition, the receptor does not work properly, so these signals cannot be sent, leaving the patient always hungry.

Leptin receptor deficiency is a long-term debilitating and life-threatening disease because it leads to severe obesity and related complications.

At the time of designation, leptin receptor deficiency affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 people^1/, 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).

At the time of designation, no satisfactory treatments were authorised in the EU for leptin receptor deficiency. Patients were managed with medicines for general weight control, or by surgery.

In patients with leptin receptor deficiency a signal cannot be sent to the nerves that control appetite. Setmelanotide is a small molecule that is expected to work by stimulating these nerves directly, bypassing the need for a signal triggered by leptin. This is expected to restore appetite control in patients with leptin receptor deficiency and so reduce their food intake and weight gain.

The effects of setmelanotide have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with setmelanotide in patients with leptin receptor deficiency were ongoing.

At the time of submission, setmelanotide was not authorised anywhere in the EU for leptin receptor deficiency. Orphan designation of the medicine had been granted in the United States for LEPR deficiency obesity.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 October 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.