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Interested in starting a patient on IMCIVREE? It's only available through our specialty pharmacy.
Download and complete the Start Form

 

Indication

IMCIVREE is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to Bardet-Biedl syndrome (BBS).

Limitations of Use

IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:

  • Other types of obesity not related to BBS or other FDA-approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity
IMCIVREE delivered early, significant, and sustained reductions in measures of weight and hunger in BBS1,3

Weight reduction1

  • ~8% mean reduction in BMI in patients ≥6 years of age after 1 year1
    • Patients were not required to change their diet or exercise routine3
  • Clinically significant -0.8 mean change in BMI Z-score in patients <18 years of age3*
    • 100% of patients <12 years of age with BBS achieved a clinically significant ≥0.2 reduction in BMI Z-score (n=3)3,4
  • Clinically significant ~10% mean weight reduction in patients ≥18 years of age3

Hunger reduction

  • Statistically significant reduction in maximal hunger score1

Safety profile

  • The most common adverse reactions in IMCIVREE-treated patients were hyperpigmentation disorders, injection site reactions, and nausea1
    • Reported incidences of nausea and vomiting primarily occurred within the first month of treatment, then sharply declined after 4 weeks. Nearly all nausea or vomiting events were mild and none were serious2
  • Depression and suicidal ideation, as well as disturbances in sexual arousal, may also occur during treatment with IMCIVREE1
  • Treatment with IMCIVREE is not recommended during breastfeeding. Patients should not take IMCIVREE while pregnant unless the benefits of therapy outweigh the potential risks1
  • Adverse events (AEs) were generally mild and transient3
  • No serious AEs related to IMCIVREE were reported in the BBS trial3

Study design: The efficacy and safety of IMCIVREE for the reduction of weight and hunger in patients with BBS were studied in a 66-week phase 3 clinical trial, which included a 14-week randomized, double-blind, placebo-controlled period and a 52-week open-label period. The study enrolled patients aged 6 years and older with obesity and a clinical diagnosis of BBS.1,3

*A clinically significant reduction is generally considered a ≥0.2 reduction in BMI Z-score. A 0.2 reduction is comparable to weight loss of approximately 5%.4

†Patients ≥12 years of age who were able to self-report their hunger (n=14) recorded their daily maximal hunger in a diary, which was then assessed by the Daily Hunger Questionnaire Item 2. Hunger was scored on an 11-point scale from 0 (“not hungry at all”) to 10 (“hungriest possible”).1


References: 1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 2. Eneli I et al. Appl Clin Genet. 2019;12:87-93. 3. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA. 4. Grossman DC et al; US Preventive Services Task Force. JAMA. 2017;317(23):2417-2426.

Mechanism of Action

THE MELANOCORTIN-4 RECEPTOR (MC4R) SIGNALING PATHWAY REGULATES APPETITE AND ENERGY EXPENDITURE1-3

Interrupted MC4R Pathway Interrupted MC4R Pathway

Genetic variants in this pathway can lead to insatiable
hunger and severe obesity

In patients with obesity due to POMC, PCSK1, or LEPR deficiency the first and only treatment to target a root cause of obesity

IMCIVREE may restore function in the signaling cascade responsible for regulating hunger, caloric intake, energy expenditure, and, consequently, body weight1-4

Fixed MC4R Pathway Fixed MC4R Pathway

IMCIVREE is designed to re-establish MC4R pathway function4
POMC, PCSK1, and LEPR deficiency are biallelic genetic diseases that include homozygous and compound heterozygous genotypes5

LEPR, leptin receptor; MSH, melanocyte-stimulating hormone; PCSK1, proprotein convertase subtilisin/kexin type 1; POMC, pro-opiomelanocortin.

TRIAL OVERVIEW

IMCIVREE WAS STUDIED IN 2 IDENTICALLY DESIGNED, 1-YEAR, OPEN-LABEL STUDIES, EACH WITH AN 8-WEEK, DOUBLE-BLIND WITHDRAWAL PERIOD4,5

Trial Overview Trial Overview
Primary endpoint:
  • Proportion of participants who achieve ≥10% weight loss at 1 year of treatment (POMC or PCSK1, N=10; LEPR, N=11)

aOnly participants who lost ≥5 kg weight (or ≥5% of body weight if baseline weight was <100 kg) in the first open-label active treatment phase entered an 8-week, double-blind withdrawal period.


BASELINE CHARACTERISTICS IN THE IMCIVREE TRIALS4,5

Baseline Characteristics Baseline Characteristics

BMI, body mass index; LEPR, leptin receptor; PCSK1, proprotein convertase subtilisin/kexin type 1; POMC, pro-opiomelanocortin; SD, standard deviation.

Efficacy

In patients with obesity due to POMC, PCSK1, or LEPR deficiency IMCIVREE delivered significant, clinically meaningful weight loss over 1 year4

Mean % change in body weight over 1 year

POMC or PCSK1 (n=9)*
  • 23.1% mean reduction in weight from baseline after 1 year
    (95% CI: -31.9%, -14.4%); P=0.0003; N=10
  • 80% of patients with obesity due to POMC or PCSK1 deficiency achieved a ≥10% weight loss from baseline after 1 year
    (95% CI: 44.4%, 97.5%); P<0.0001; N=10
LEPR (n=7)*
  • 9.7% mean reduction in weight from baseline after 1 year
    (95% CI: -16.0%, -3.3%); P=0.0074; N=11
  • 45.5% of patients with obesity due to LEPR deficiency achieved a ≥10% weight loss from baseline after 1 year
    (95% CI: 16.8%, 76.6%); P=0.0002; N=11

In both studies, weight increased during the withdrawal period, then decreased once treatment was reinitiated4

BL, baseline; CI, confidence interval; FV, final visit; LEPR, leptin receptor; PCSK1, proprotein convertase subtilisin/kexin type 1; POMC, pro-opiomelanocortin.
*Participants who achieved weight loss threshold (≥5 kg or 5% if baseline body weight was <100 kg) during the 10-week open-label period.
†The withdrawal period lasted 8 weeks, which included 4 weeks of IMCIVREE followed by 4 weeks of placebo.


In patients with obesity due to POMC, PCSK1, or LEPR deficiency IMCIVREE decreased hunger over 1 year4

Median change in maximal hunger score over 1 year

POMC or PCSK1 (n=8)*
  • In patients with obesity due to POMC or PCSK1 deficiency, IMCIVREE demonstrated a median 2-point reduction in maximal hunger score at 1 year
    (Range: -6.5, -0.1)
LEPR (n=8)*†
  • In patients with obesity due to LEPR deficiency, IMCIVREE demonstrated a median 3.4-point reduction in maximal hunger score at 1 year
    (Range: -4.7, 1.0)

When treatment was withdrawn, hunger scores generally worsened and then improved when IMCIVREE was reinitiated4

LEPR, leptin receptor; PCSK1, proprotein convertase subtilisin/kexin type 1; POMC, pro-opiomelanocortin.
*Changes in patient-reported maximal hunger over the previous 24 hours were assessed by the Daily Hunger Questionnaire item 2 for subjects aged ≥ 12 years, with a hunger score ranging from 0 (not hungry at all) to 10 (hungriest possible). The median score at baseline (and week 52) was determined by calculating the average week 1 score (and average week 52 score) for each patient and determining for the median for the group.
†Three patients had missing hunger data at 1 year.

Safety

Adverse reactions

Adverse reactions occurring in ≥23% of patients treated with IMCIVREE in open-label clinical studies of 1-year duration4

  • IMCIVREE is an MC4 receptor 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 treatment4
  • Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new skin pigmentary lesions4
  • Changes in skin pigmentation or hair color primarily occurred within the first month of treatment7
  • Injection site reactions, nausea, and vomiting most often occurred within the first month after starting treatment, and then decreased over time7

An extension study evaluating long-term outcomes for
patients on IMCIVREE is ongoing6

SEE DOSING & ADMINISTRATION

aIncludes injection site erythema, pruritus, edema, pain, induration, bruising, hypersensitivity, hematoma, nodule, and discoloration.
bIncludes skin hyperpigmentation, pigmentation disorders, and skin discoloration.
cIncludes abdominal pain and upper abdominal pain.
dIncludes depressed mood.
en=13 male patients.

References: 1. Yazdi FT et al. PeerJ. 2015;3:e856. 2. Shen W-J et al. Biochim Biophys Acta Mol Basis Dis. 2017;1863:2477-2485. 3. Farooqi IS, O’Rahilly S. J Endocrinol. 2014;223:T63-T70. 4. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 5. Clément K et al. Lancet Diabetes Endocrinol. 2020 Dec;8(12):960-970. doi: 10.1016/S2213-8587(20)30364-8. Epub 2020 Oct 30. PMID: 33137293. 6. Long term extension trial of setmelanotide. ClinicalTrials.gov identifier: NCT03651765. Updated December 31, 2020. Accessed January 5, 2021. https://clinicaltrials.gov/ct2/show/NCT03651765. 7. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA.

Important Safety Information
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WARNINGS AND PRECAUTIONS

Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.

Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.

Indication

IMCIVREE is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to: