IMCIVREE (setmelanotide) - POMC

Reassessment.

Key points

Favourable opinion for reimbursement in the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic pro-opiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above.

What therapeutic improvement?

Clinical added value in the therapeutic strategy on the basis of currently available data.

Role in the care pathway?

The management of obesity is complex and requires a multidisciplinary approach combining dietary measures, physical activity and, if necessary, psychological follow-up.

Beyond standard dietary measures and lifestyle changes, early onset obesity is difficult to treat. Conventional obesity treatments are sometimes insufficient (behavioural approach, surgical or medicinal treatments, environmental changes) and there is no treatment to manage hyperphagia.

Hence, bariatric surgery cannot address the underlying issue of the lack of a satiety signal in these patients and therefore cannot control the patient’s hunger or obesity. The other potential surgical approaches, such as gastric or intestinal bypass operations, are considered to be contraindicated because such patients maintain an extreme appetite and overeat even after such surgical procedures, often leading to anatomical complications as a result.

In its guidelines, the HAS points out that bariatric surgery is not indicated in adolescents with severe and non-stabilised eating disorders, addictive behaviours or in patients with syndrome-related (for example, Prader-Willi syndrome), known monogenetic, or lesion-related obesity (apart from exceptions).

Endocrine therapies, particularly in patients with a POMC/PCSK1 deficiency, are often necessary (life-long glucocorticosteroid replacement therapy, treatment for possible hypothyroidism).

There are currently no clinical guidelines for the treatment or management of obesity related to a POMC or LEPR deficiency.

Role of the medicinal product in the care pathway

Despite limited data from two non-comparative, open-label studies concerning a small number of patients, in the context of a very rare disease, the Committee considers that IMCIVREE
(setmelanotide) is a first-line treatment for obesity and the control of hunger when it is associated with a biallelic pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin
Type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency in adults and children 6 years of age and above.

Setmelanotide can cause a generalised increase in skin pigmentation and darkening of pre-existing nevi because of its pharmacologic effect. Full body skin examinations should be conducted annually to monitor pre-existing and new skin pigmentary lesions before and during treatment with setmelanotide.

In clinical trials, depression has been reported in patients treated with setmelanotide. However, this AE was not considered to be treatment-related. In accordance with the SmPC, patients with depression should therefore be monitored at each medical visit during treatment with IMCIVREE
(setmelanotide) and consideration should be given to discontinuing IMCIVREE (setmelanotide) if patients experience suicidal thoughts or behaviours.

The new data submitted do not modify the role of IMCIVREE (setmelanotide) in the care pathway.

Special recommendations

Considering:

• that obesity, even genetic, requires multidisciplinary management,
• current uncertainties with respect to the long-term safety of the product, particularly given the dermatological and psychiatric adverse events,

the Committee recommends that the decision to initiate setmelanotide treatment be taken at a multidisciplinary team (MDT) meeting and in reference centres. Particular attention must be paid to the dermatological and psychological follow-up of patients on setmelanotide.