IMCIVREE was studied across three open-label, Phase 3 clinical trials in patients with POMC, PCSK1, or LEPR deficiency1-3

IMCIVREE was studied in the first-ever Phase 3 clinical trial for children 2 to <6 years of age with obesity due to POMC, PCSK1, or LEPR deficiency1,2,4*

IMCIVREE trial design

Endpoints:

  • Mean percent change in BMI from baseline to Week 52 (primary endpoint)
  • Proportion of participants with a decrease in BMI Z-score of ≥0.2 at Week 52 (POMC, N=3; LEPR, N=4)

*Efficacy and safety analyses were conducted at the end of treatment in 12 patients (7 with POMC or LEPR deficiency and 5 with BBS). Patients with PCSK1 deficiency were eligible but none enrolled in the trial.

IMCIVREE was studied in 2 identically designed, 1-year, open-label studies, each with an 8-week, double-blind withdrawal period in patients 6 years and older with obesity due to POMC, PCSK1, and LEPR deficiency1,3

IMCIVREE trial design

Primary endpoint:

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

*Only 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 these IMCIVREE trials1,3,4

IMCIVREE trial baseline characteristics

*LEPR=leptin receptor; PCSK1=proprotein convertase subtilisin/kexin type 1;
POMC=proopiomelanocortin; SD=standard deviation.

Learn more about the efficacy of IMCIVREE

References: 1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 2. Argente J, Verge CF, Okorie U, et al. Setmelanotide in patients aged 2–5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Lancet Diabetes Endocrinol. 2024;24:1-18. doi: 10.1016/s2213-8587(24)00273-0. 3. Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 2020;8(12):960-970. doi:10.1016/S2213-8587(20)30364-8. 4. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA.

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

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:

  • Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign
  • Other types of obesity not related to POMC, PCSK1, or LEPR deficiency, or other FDA- approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity
Important Safety Information

CONTRAINDICATIONS

Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported.

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, suicidal ideation, and depressed mood 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.

Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE.

Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increased skin pigmentation, darkening of pre-existing nevi, development of new melanocytic nevi and increase in size of existing melanocytic nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions.

Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs.

ADVERSE REACTIONS

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection

USE IN SPECIFIC POPULATIONS

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at 833-789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for additional Important Safety Information.

Important Safety Information

Indication

IMCIVREE is indicated to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS).

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:

  • Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign
  • Other types of obesity not related to POMC, PCSK1, or LEPR deficiency, or other FDA- approved indications for IMCIVREE, including obesity associated with other genetic syndromes and general (polygenic) obesity
Important Safety Information

CONTRAINDICATIONS

Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported.

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, suicidal ideation, and depressed mood 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.

Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE.

Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increased skin pigmentation, darkening of pre-existing nevi, development of new melanocytic nevi and increase in size of existing melanocytic nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions.

Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs.

ADVERSE REACTIONS

  • Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection

USE IN SPECIFIC POPULATIONS

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at 833-789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for additional Important Safety Information.