Target the root,
restore the balance
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.
IMCIVREE SmPC/Prescribing information
IMCIVREE, a precision medicine targeting impairment in the MC4R pathway, a root cause of hyperphagia and early-onset, severe obesity.1
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 old of age and above.1
BBS is a rare syndromic ciliopathy that presents with a variety of clinical features, which may include hyperphagia (pathological, insatiable hunger) and early-onset, severe obesity arising from impairment of the melanocortin-4 receptor (MC4R) pathway.2-4
To find out more background on BBS,
72% to 92% of patients with BBS present with obesity, and hyperphagia may be a contributing factor. Obesity can worsen comorbidities, such as diabetes mellitus, cardiovascular disease, and sleep disorders, further complicating clinical management.2-4
STUDY DESIGN
IMCIVREE was studied in a multicentre, randomised, 14-week double-blind, placebo-controlled, phase 3 trial followed by a 52-week open-label period, in patients with Bardet-Biedl syndrome or Alström syndrome and obesity.7
Primary endpoint:
The proportion of patients who achieve a ≥ 10% reduction from baseline in body weight after ~52 weeks ≥ 10% of treatment with IMCIVREE.6
Key secondary endpoints:
Mean percentage change from baseline in body weight and in the once per week average of the daily hunger score, and the proportion of patients who reached at least a 25% reduction in the once per week average of the daily hunger score from baseline after 52 weeks. Mean percentage change from baseline in body weight and once per week average of the daily hunger score at week 14 compared with placebo. Frequency and severity of adverse events.6

Paediatric data

IMCIVREE can treat hyperphagia and early-onset, severe obesity in patients ≥ 6 years old and older with genetically confirmed Bardet-Biedl syndrome*
​​
Sustained BMI Z-score reduction patients < 18 years old

  • Sustained BMI Z-score reduction up to 52 weeks†

    • Improved quality of life in patients < 18 years old

  • Studied as exploratory endpoints measured by improvements in physical function and psychosocial scores‡

    • Generally well-tolerated

  • Most frequent adverse events were hyperpigmentation disorders, injection site reactions, nausea, and headache§

    • Primary endpoint: After 52 weeks, 32.3% (95% CI 16.7,51.4; p=0.0006) of those ≥12 years old reached at least a 10% reduction in body weight.6

    *

    IMCIVREE 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 six years of age and above.1

    †

    After 52 weeks, 71% of those <18 years old reached a 0.3, or greater, reduction in BMI Z-score (mean 0.8)6

    ‡

    All patients with baseline quality of life impairment experienced clinically meaningful (defined as total score change >4.4) improvement and reported improvements in physical function and psychosocial scores.7

    §

    The most frequent adverse reactions are hyperpigmentation disorders (56%), injection site reactions (45%), nausea (31%), and headache (20%).1

    Sustained BMI Z-score reduction in patients under < 18 years old6
    IMCIVREE delivered significant and clinically meaningful reduction in BMI Z-score over 1 year6
    After 52 weeks of IMCIVREE, 32.3% of patients ≥ 12 years of age reached the primary endpoint of at least a 10% reduction in bodyweight6
    ​​

    *

    Mean percentage change in BMI Z-score in patients with Bardet-Biedl syndrome.

    Error bars show the SD. Data shown by study visit do not include data imputed for patients who received less than 52 weeks of IMCIVREE at the time of analysis. Active treatment baseline is defined as the last measurement before the first dose of IMCIVREE (ie., week 0 for the IMCIVREE group and week 14 for the placebo group).

    BMI Z-score absolute change in pivotal patients with Bardet-Biedl syndrome younger than 18 years (population size range 8-16; n=14 at 52 weeks on active treatment).

    PCPB, placebo-controlled period baseline.

    Improved quality of life in patients under <18 years old
    All patients with baseline quality of life impairment experienced clinically meaningful (defined as total score change >4.4) improvement and reported improvements in physical function and psychosocial scores.7
    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

    12 years and older data

    IMCIVREE can treat hyperphagia and early-onset, severe obesity in patients ≥ 12 years old with genetically confirmed Bardet-Biedl syndrome*
    ​​
    Early hunger reduction and sustained weight reduction

  • Early hunger reduction from 14 weeks onwards†

    Sustained weight reduction up to 52 weeks‡

    • Improved quality of life in patients ≥18 and older

  • Studied as exploratory endpoints across five domains (physical function, self-esteem, public distress, sex life and work)§

    • Generally well-tolerated

  • Most frequent adverse events were hyperpigmentation disorders, injection site reactions, nausea, and headache||

    • *

    IMCIVREE 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

    †

    After 14 weeks, IMCIVREE patients ≥12 years old had an average 14.4% (95% CI: 31.9%, −3.14%; p=0.051) greater reduction in the weekly average of the daily maximal hunger score and 12.2% (95% CI: 32.4%, −7.9%; p=0.1081) greater reduction in the weekly morning average hunger.6

    ‡

    After 52 weeks, 32.3% (95% CI 16.7-51.4; p=0·0006) of those ≥12 years old reached at least a 10% reduction in body weight.6

    §

    62.5% of patients ≥18 years old with quality-of-life impairment experienced clinically meaningful improvement. Quality of life score significantly correlated with percent body weight (P=0.0037) and BMI (P=0.0098) changes.7

    ||

    The most frequent adverse reactions are hyperpigmentation disorders (56%), injection site reactions (45%), nausea (31%), and headache (20%).1

    IMCIVREE delivered significant and clinically meaningful weight loss over 1 year6
    After 52 weeks of IMCIVREE, 32.3% of patients ≥ 12 years of age reached the primary endpoint of at least a 10% reduction in bodyweight6
    In BBS patients ≥ 18 years of age:

    47% achieved >10% reduction in body weight6

    60% achieved >5% reduction in body weight at 52 weeks6

    Mean percentage change in bodyweight in patients with BBS*

    *

    Error bars show the SD. Data shown by study visit do not include data imputed for patients who received less than 52 weeks of IMCIVREE at the time of analysis. Active treatment baseline is defined as the last measurement before the first dose of IMCIVREE (ie, week 0 for the IMCIVREE group and week 14 for the placebo group). Bodyweight percentage change in the exploratory cohort of patients with Bardet-Biedl syndrome aged ≥ 18 years old (population size range 7-15; n=12 at 52 weeks on active treatment).

    IMCIVREE delivered early, significant and sustained hunger reduction over 1 year, in patients ≥ 12 years old

    After 14 weeks, IMCIVREE patients ≥12 years old had an average 14.4% (95% CI: 31.9%, −3.14%; p=0.051) greater reduction in the weekly average of the daily maximal hunger score and 12.2% (95% CI: 32.4%, −7.9%; p=0.1081) greater reduction in the weekly morning average hunger.6

    57% of patients reached ≥25% in their hunger score after 52 weeks of treatment with IMCIVREE, with a mean percentage change in maximal hunger score of −30.5% (SD 26.5%; −45.7% to−15.2%; p=0.0004).6

    71% reached the clinically meaningful reduction in daily maximal hunger score of at least 1 point and 43% reached a reduction of 2 points or higher.6

    Hunger score changes in pivotal patients with BBS*

    *

    Grey bars indicate titration and re-titration periods. Hunger scores are reported in patients ≥12 years old without cognitive impairment. PCPB, placebo-controlled period baseline.

    Improved quality of life in patients ≥ 18 years old
    Studied as exploratory endpoints across five domains (physical function, self-esteem, public distress, sex life and work)7
    62.5%
    of patients ≥18 years old with quality-of-life impairment experienced clinically meaningful improvement.
    Quality of life score significantly correlated with percent body weight (P=0.0037) and BMI (P=0.0098) changes7
    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

    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. Forsythe E, Beales PL. Eur J Hum Genet 2013;21(1):8–13.
    3. Sherafat-Kazemzadeh R, et al. Int J Obes (Lond). 2013;37(1):1–15.
    4. Pigeyre M, et al. Clin Sci (Lon).2016;130:943–986.
    5. Forsythe E, et al. Front Pediat. 2018:6:23.
    6. Haqq AM, et al. Lancet Diabetes Endocrinol. 2022;10(12):859–868.
    7. Forsythe E, et al. Orphanet J Rare Dis. 2023;18(1):12..