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Imcivree based on Setmelanotide in adults and children aged 6 years and older with Bardet Biedl syndrome, and in patients with POMC or LEPR deficiency

Imcivree is a medicine used to treat obesity and help control hunger caused by certain genetic conditions that affect how the brain controls feelings of hunger. It is used in adults and children aged 6 years and older with Bardet Biedl syndrome ( BBS ), and in those who have pro-opiomelanocortin ( POMC ) deficiency or leptin receptor ( LEPR ) deficiency resulting from mutations in both copies of the genes responsible for making POMC or LEPR.

Bardet Biedl syndrome, pro-opiomelanocortin deficiency and leptin receptor deficiency are rare, and Imcivree was designated an orphan medicine ( a medicine used in rare diseases ).

Imcivree contains the active substance Setmelanotide.

Imcivree is given once a day as an injection under the skin. The dose depends on the condition being treated, the effect of the treatment and how well it is tolerated. After being trained, patients or carers can inject the medicine themselves.

People with POMC deficiency have low levels of pro-opiomelanocortin, a substance that is converted into several hormones, including melanocyte-stimulating hormone ( MSH ). Low levels of MSH lead to loss of feeling of fullness after eating.
In people with LEPR deficiency, the receptor for the hormone leptin does not work properly so signals to the nerves that make the body feel full and control feelings of hunger cannot be sent.
People with POMC, LEPR deficiency and BBS feel continuously hungry and quickly put on weight.

The active substance in Imcivree, Setmelanotide, attaches to and activates a receptor called melanocortin receptor 4, which is normally activated through leptin and MSH, promoting a feeling of fullness after eating. By attaching to this receptor directly, Setmelanotide is expected to reduce excessive food intake and obesity.

In 2 main studies, Setmelanotide was shown to be effective at reducing body weight by at least 10% in people with POMC and LEPR deficiency.

The first study was carried out in 10 patients with obesity due to POMC deficiency resulting from mutations in both copies of the genes for either POMC or PCSK1. After one year of treatment, 8 out of 10 people achieved at least a 10% reduction in body weight.

In the second study carried out in 11 patients with obesity due to LEPR deficiency caused by mutations in both copies of the gene for LEPR, 5 people out of 11 achieved at least a 10% reduction in body weight after one year.

The studies also looked at the effects of Setmelanotide on the feeling of hunger as measured using a questionnaire: the percentage of patients who achieved at least a 25% reduction in hunger scores was 50% in the first study, and 73% in the second study.

In a study that has included 28 patients aged 12 years or older with BBS, around 36% of the patients achieved at least a 10% reduction in body weight after one year of treatment.

Imcivree was not compared to another medicine in these studies.

The most common side effects with Imcivree ( which may affect more than 1 in 10 people ) are hyperpigmentation ( coloration of the skin ), injection site reaction, nausea ( feeling sick ), and headache.

The number of people with BBS, POMC or LEPR deficiency is extremely small, so the number of people included in the studies was very limited.
However, the studies have shown that Imcivree helps to reduce bodyweight and feelings of hunger in these patients. These benefits are considered significant considering that there are no other medicines for these patients.
Imcivree’s side effects are manageable and long-term safety is monitored in a dedicated study after authorisation.

The European Medicines Agency ( EMA ) has therefore decided that Imcivree’s benefits are greater than its risks. ( Xagena )

Source: EMA, 2021