IMCIVREE has a well-established safety and tolerability profile1,2

Adverse reactions occurring in ≥23% of people treated with IMCIVREE in open-label clinical studies of 1-year duration for POMC, PCSK1, or LEPR deficiency1,2

Adverse reaction1N=27 (%)
Injection site reaction*96%
Skin hyperpigmentations†78%
Nausea56%
Headache41%
Diarrhea37%
Abdominal pain‡33%
Adverse reaction1N=27 (%)
Back pain33%
Fatigue30%
Vomiting30%
Depression§26%
Upper respiratory tract infection26%
Spontaneous penile erection||23%

*Includes injection site erythema, pruritus, edema, pain, induration, bruising, hypersensitivity, hematoma, nodule, and discoloration.1

†Includes skin hyperpigmentation, pigmentation disorders, and skin discoloration.1

‡Includes abdominal pain and upper abdominal pain.1

§Includes depressed mood.1

||n=13 male patients.1

  • Reported incidences of nausea and vomiting primarily occurred within the first month of treatment, then decreased over time2
  • Reported incidences of nausea and vomiting typically resolved within a few days in patients with a rare genetic disease of obesity in IMCIVREE clinical trials2
  • Nausea and vomiting should be managed by dose titration and standard care1
  • The safety of IMCIVREE has been evaluated in >700 patients over ~10 years of clinical trials3,4

An extension study evaluating long-term outcomes for patients on IMCIVREE is ongoing5

  
Warnings and precautions

Hyperpigmentation was common but rarely led to discontinuation1,6

  • Changes in skin pigmentation or hair color typically presented within the first 2 to 3 weeks of treatment with IMCIVREE8,9
    • Skin darkening plateaued during the course of treatment and was not dose-dependent7
    • Hyperpigmentation is variable7
    • This effect is reversible after discontinuation of treatment1
    • Perform a full body skin examination prior to initiation and periodically during treatment with IMCIVREE to monitor pre-existing and new skin pigmentary lesions1
    • Hyperpigmentation is not unexpected given that IMCIVREE also activates the melanocortin-1 receptor, which results in melanin production1
See dosing and administration

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

References: 1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 2. Argente J et al. The Pediatric Endocrine Society Annual Meeting. Poster 155. April 28-May 1, 2022. 3. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA. 4. U.S. National Library of Medicine. Identifier: NCT02431442. ClinicalTrials.gov. Accessed August 14, 2023. https://www.clinicaltrials.gov/ct2/show/study/NCT02431442. 5. U.S. National Library of Medicine. Identifier: NCT03651765. ClinicalTrials.gov. Accessed August 14, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03651765. 6. Clément K et al. Lancet Diabetes Endocrinol. 2020;8(12):960-970. 7. Clément K et al. Lancet Diabetes Endocrinol. [Supplementary appendix] 2020;8(12):960-970.

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 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 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.

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

Skin Pigmentation and Darkening of Pre-existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmentary 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 the full Prescribing Information for additional Important Safety Information.

Important Safety Information

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 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 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.

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

Skin Pigmentation and Darkening of Pre-existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmentary 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 the full Prescribing Information for additional Important Safety Information.