Target the root, restore the balance
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IMCIVREE SmPC/Prescribing information
IMCIVREE is the first and only therapy to treat the root cause of hyperphagia and obesity in pro-opiomelanocortin (POMC), PCSK1 and leptin receptor (LEPR) deficiency by re-establishing melanocortin-4 receptor (MC4R) pathway activity to reduce hunger and promote weight loss1
In patients with obesity due to POMC, PCSK1, or LEPR deficiency, IMCIVREE:
is designed to re-establish MC4R pathway activity in the hypothalamus to reduce hunger (hyperphagia [pathological, insatiable hunger]) and promote weight loss through decreased caloric intake and increased energy expenditure1
delivered significant, clinically meaningful weight loss over 1 year2
decreased hunger over 1 year2
was generally well-tolerated across multiple development programs (most frequent adverse events are hyperpigmentation [56%], injection site reaction [45%], nausea [31%] and headache [20%]1
To find out more about POMC, PCSK1 and LEPR deficiency please
IMCIVREE (setmelanotide) is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed Bardet-Biedl syndrome (BBS), 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.1
IMCIVREE was studied in two phase 3 open-label single-arm, multicentre trials evaluating the efficacy of IMCVIREE for reducing body weight and hunger in individuals with obesity due to POMC deficiency or LEPR deficiency2
The primary endpoint, assessed in participants who received at least one dose of study medication and had a baseline assessment (full analysis set), was the proportion of participants with at least 10% weight loss compared with baseline at approximately 1 year.2
*The withdrawal period lasted 8 weeks, which included 4 weeks of IMCIVREE followed by 4 weeks of placebo.
IMCIVREE delivered significant, clinically meaningful weight loss over 1 year2
80%
of patients with obesity due to POMC or PCSK1 deficiency achieved a ≥10% weight loss from baseline after 1 year (primary endpoint)
(90% CI: 49.31%, 96.32%); P<0.0001; N=102
45%
of patients with obesity due to LEPR deficiency achieved a ≥10% weight loss from baseline after 1 year (primary endpoint)
(90% CI: 19.96%, 72.88%); P=0.0002; N=112
Mean % change in body weight over 1 year2
25.6%
mean reduction in weight from baseline after 1 year
(90% CI: -28.80%, -21.98%); P<0.0001; N=92
12.5%
mean reduction in weight from baseline after 1 year
(90% CI: -16.10%, -8.83%); P<0.0001; N=72
In both studies, weight increased during the withdrawal period, then decreased once treatment was reinitiated†*2
†  The withdrawal period lasted 8 weeks, which included 4 weeks of IMCIVREE followed by 4 weeks of placebo.
*Participants who achieved weight loss threshold (≥5 kg or 5% if baseline body weight was <100 kg) during the 10-week open-label period
IMCIVREE decreased hunger over 1 year2
27.1%
POMC: Most hunger score reduced by 27.1%
(key secondary endpoint)†*2

  • The mean percentage change in the most hunger score was −27.1% (n=7; 90% CI −40.6 to −15.0; P=0.0005), which is clinically meaningful2

  • 50% of participants achieved a predefined clinically meaningful ≥25% improvement in hunger score from baseline at 1 year2

  • When IMCIVREE was withdrawn in participants who had lost weight during the 10-week open-label period, the mean hunger scores increased over the 4 weeks of placebo treatment2

43.7%
LEPR: Most hunger score reduced by 43.7%
(key secondary endpoint)†*2

  • The mean percentage change in the most hunger score was −43·7% (n=7; −54.8 to −29.1; P<0.0001)2

  • 73% of participants achieved a predefined clinically meaningful ≥25% improvement in hunger score from baseline at 1 year2

  • When IMCIVREE was withdrawn in participants who had lost weight during the 10-week open-label period, the mean hunger scores increased over the 4 weeks of placebo treatment2

When treatment was withdrawn, hunger scores generally worsened and then improved when IMCIVREE was reinitiated2
*Mean percentage change in the most hunger score of the 11-point Likert-type scale at approximately 1 year on the therapeutic dose was assessed in a subset of participants aged 12 years or older in the full analysis set who demonstrated at least 5 kg weight loss (or ≥5% in paediatric participants if baseline body weight was <100 kg) over the 12-week open-label treatment phase and subsequently proceeded into the placebo-controlled withdrawal sequence, regardless of later disposition.
†Study week is reported relative to baseline and includes time during the dose titration phase. Error bars are the 90% CI. Seven participants were included in the analysis for all study weeks.
IMCIVREE is generally well-tolerated.1
The most common adverse events (AEs) associated with IMCIVREE included skin hyperpigmentation and injection site reactions.1

Hyperpigmentation disorders

56%

Injection site reactions

45%

Nausea

31%

Headache

20%

  • IMCIVREE is an MC4R agonist with some activity at the melanocortin 1 (MC1) receptors. Activation of MC1 leads to accumulation of melanin and increased skin pigmentation. This effect is reversible upon discontinuation of treatment1

  • Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new skin pigmentary lesions1

  • Changes in skin pigmentation or hair colour primarily occurred within the first month of treatment1

  • Injection site reactions, nausea, and vomiting most often occurred within the first month after starting treatment, and then decreased over time1

In the clinical trials:
No serious treatment-related AEs were reported2
There was no treatment-related worsening of depression2
IMCIVREE is a once-daily, subcutaneous injection that can be administered at home1
The injection should be given at the start of the day to maximise hunger reduction when awake and can be taken regardless of the timing of meals1
If dose escalation is not tolerated, paediatric patients may maintain administration of the 0.5 mg once daily dose.

The prescribing physician should periodically assess response to IMCIVREE therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated.
Missed dose
If a dose is missed, the once daily regimen should be resumed at the dose prescribed with the next scheduled dose.1
For patients with severe renal impairments and BBS patients, a separate dosage scheme applies.1
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All adverse events should be reported. For medical information, to report an adverse event or product complaint please contact eu_medinfo@rhythmtx.com

References:

  1. IMCIVREE Summary of Product Characteristics. March 2023.
  2. Clément K, et al. Lancet Diabetes Endocrinol 2020.