Setmelanotide has been authorised in the EU as Imcivree since 16 July 2021.

On 19 November 2018, orphan designation (EU/3/18/2101) was granted by the European Commission to TMC Pharma Services Ltd, United Kingdom, for setmelanotide 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 people1/, 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).


1Disclaimer: 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 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.

Key facts

Active substance
Intended use
Treatment of leptin receptor deficiency
Orphan designation status
EU designation number
Date of designation

Rhythm Pharmaceuticals Netherlands B.V.

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Imcivree at the time of marketing authorisation, and confirmed that the orphan designation should be maintained. 

More information is available in the orphan medicine assessment report.

Update history

July 2022The sponsor's address was updated.
October 2021The sponsorship was transferred to Rhythm Pharmaceuticals Netherlands B.V. in October 2021.
November 2020The sponsorship was transferred to Rhythm Pharmaceuticals Limited, Ireland, in November 2020.
March 2019The sponsorship was transferred to TMC Pharma (EU) Limited, Ireland, in March 2019.

EMA list of opinions on orphan medicinal product designation

EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.

EU register of orphan medicines

The list of medicines that have received an orphan designation in the EU is available on the European Commission's website:

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