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Start Form

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

Start Form

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.

PATIENT SUPPORT

A support program designed for caregivers and people living with a rare genetic disease of obesity

A Patient Education Manager is a single point of contact at Rhythm who can help patients and caregivers:

Rhythm InTune resources

Access educational resources, such as virtual education programs about rare genetic diseases of obesity or treatment with IMCIVREE.

Rhythm InTune community

Connect to a community, where they can learn from the experiences of others.

Rhythm InTune coverage

Access treatment, by helping with understanding drug coverage, prior authorizations, appeals support, and for eligible patients, copay support and financial assistance.

Rhythm InTune calendar

Get started on treatment by coordinating IMCIVREE deliveries and injection support with the specialty pharmacy.

For more information about Rhythm InTune or to request support, contact us at:

Interested in starting a patient on IMCIVREE?
Download and complete the Start Form


FINANCIAL SUPPORT MAY BE AVAILABLE FOR QUALIFIED PATIENTS FOR WHOM IMCIVREE IS INDICATED

Co-pay assistance program

  • May help cover out-of-pocket costs associated with IMCIVREE, up to $8550 per year
  • To be eligible, patients must have a commercial insurance policy and a prescription for IMCIVREE

Patient assistance program

Can help individuals who are:

  • uninsured,
  • who have temporarily lost insurance coverage, or
  • whose insurance doesn't cover IMCIVREE

PATIENT RESOURCES

WE ARE COMMITTED TO PROVIDING SUPPORT TO YOU AND YOUR PATIENTS

Resources are available on the IMCIVREE patient website, www.IMCIVREE.com

STARTING IMCIVREE

GETTING YOUR PATIENT STARTED ON IMCIVREE

3 simple steps to initiate treatment

Download the IMCIVREE Start Form at IMCIVREE.com/start

1. Download the IMCIVREE Start Form at IMCIVREE.com/start*

2. Follow the instructions to complete the form

3. Submit all pages of the completed form via fax to 1-877-805-0130 or email patientsupport@rhythmtx.com

*The preferred method of starting IMCIVREE is via our Start Form. If you would prefer to e-prescribe, please contact Panther Specialty Pharmacy.

IMCIVREE is only available through our specialty pharmacy

PANTHERx Specialty Pharmacy.

Financial support may be available to eligible patients for whom IMCIVREE treatment is indicated. For questions on IMCIVREE or how to start a patient, call Rhythm InTune at 1-855-206-0815 Monday—Friday, 8 AM to 8 PM ET.


GENETIC TESTING

IMCIVREE is indicated for chronic weight management in patients aged 6+ with obesity due to POMC, PCSK1, and LEPR deficiency confirmed by an FDA-approved test. These diseases are biallelic, signifying that variants are present in both copies of the gene, and therefore include both homozygous and compound heterozygous forms.

Genetic Testing

Rhythm Pharmaceuticals offers no-cost genetic testing for rare genetic diseases of obesity to eligible patients

Rhythm covers the cost of the test, with the patient responsible for any office visit, sample collection, or related costs. Additional information is available at https://UncoveringRareObesity.com or by calling PreventionGenetics at 1-844-513-3994, Monday—Friday from 9 AM to 8 PM ET.

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

FAQs

FREQUENTLY ASKED QUESTIONS ABOUT IMCIVREE

What is IMCIVREE indicated for?

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) [see Dosage and Administration (2.1)]
  • Bardet-Biedl syndrome (BBS)

Are there any contraindications to IMCIVREE?

No. There are no contraindications to IMCIVREE.1

Do I have to submit the results of genetic testing with the Start Form?

Yes, you must send your patient's genetic test results with the IMCIVREE Start Form. Rhythm Pharmaceuticals offers no-cost genetic testing for rare genetic diseases of obesity to eligible patients. Rhythm Pharmaceuticals covers the cost of the test, with the patient responsible for any office visit, sample collection, or related elements. Additional information is available at www.UncoveringRareObesity.com or by calling PreventionGenetics at 1-844-513-3994, Monday—Friday, 9 AM to 8 PM ET.

How is IMCIVREE administered?

IMCIVREE is administered by subcutaneous injection, once daily, at the beginning of each day without regard to meals.1 The process for subcutaneous injection is described in the Instructions for Use, which contains complete administration instructions with illustrations.

What part of the body should patients inject IMCIVREE into?

IMCIVREE should be injected subcutaneously in the abdomen, thigh, or arm, rotating to a different site each day. (Refer to Step 5 of the Instructions for Use.) Do not administer IMCIVREE intravenously or intramuscularly.1

What type of syringe should the patient use to administer IMCIVREE?

Prior to initiation of IMCIVREE, train patients or their caregivers on proper injection technique. Instruct patients to use a 1-mL syringe with a 28- or 29-gauge needle appropriate for subcutaneous injection.

My patient missed a dose. Does he/she need to retitrate their dose?

If a dose is missed, the once-daily regimen should be resumed as prescribed with the next scheduled dose.1

My patient discontinued treatment for an extended period of time. Do I need to retitrate the dose?

Dose titration is recommended to initially assess tolerability to the medication and to determine the therapeutic dose. In clinical studies, patients were placed on placebo for a 4-week period, then re-initiated therapy at the therapeutic dose for the remainder of the study.1

My patient accidentally administered an overdose of IMCIVREE. What adverse events should we be most concerned about?

In the event of an overdose, initiate appropriate supportive treatment according to the patient’s clinical signs and symptoms.1

How is IMCIVREE supplied?

IMCIVREE is supplied in a 1-mL, multiple-dose vial, containing 10 mg of medication. The solution should appear clear to slightly opalescent, colorless to slightly yellow.1

How should IMCIVREE be stored?

Unopened Vials

  • Refrigerator: 2°C to 8°C (36°F to 46°F) until expiration date1
  • Room temperature: 2°C to 25°C (36°F to 77°F)* for up to 30 days or until the expiration date (whichever is earlier)1

Open (in‐use) Vials: up to 30 days or until the expiration date (whichever is earlier)

  • Refrigerator: 2°C to 8°C (36°F to 46°F)1
  • Room temperature: 2°C to 25°C (36°F ‐ 77°F)*1

Always store in original carton to protect from light.1
Do not freeze.1

*Brief excursions up to 30°C (86°F) are permitted. Above 30°C (86°F), discard vials and do not use.1

Can IMCIVREE cause prolonged erections?

Spontaneous penile erections in males (24%) occurred in clinical trials with IMCIVREE. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.1

What sexual disturbances were reported in females in the clinical trials?

In a 12-week, placebo-controlled clinical study in an unapproved population, sexual adverse reactions in females (7% in IMCIVREE-treated patients and 0% in placebo-treated patients from an unapproved population) occurred in clinical studies with IMCIVREE.

Does IMCIVREE cause or worsen depression?

Patients with a history of severe depression were excluded from the clinical trials. However, some drugs that target the central nervous system, such as IMCIVREE, may cause depression or suicidal ideation. Depression occurred in (26%) of patients, and suicidal ideation occurred in (11%) occurred in adults and pediatric patients in IMCIVREE clinical studies. Patients with a history of depression or suicidal ideation may be at increased risk for recurrent episodes while taking IMCIVREE.

Monitor patients for new onset or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors or if clinically significant or persistent depression symptoms occur.

Can IMCIVREE be used with antidepressants?

No clinical studies evaluating the drug-drug interaction potential of IMCIVREE have been conducted.1

What is hyperpigmentation? Is it just skin darkening?

Hyperpigmentation can involve the darkening of skin and pre-existing nevi in the absence of ultraviolet (UV) exposure.1

Is skin darkening reversible?

Generalized increased skin pigmentation occurred in the majority of patients (69%) treated with IMCIVREE in clinical trials. IMCIVREE may also cause darkening of pre-existing nevi due to its pharmacologic effect. This effect is reversible upon discontinuation of the drug.

Why does my patient need a skin examination before starting IMCIVREE?

  • 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 pigmentation1
  • Hyperpigmentation occurred in 21 patients (78%) treated with IMCIVREE and was reversible upon discontinuation of the drug1
  • Perform a full body skin examination prior to initiation and periodically during treatment with IMCIVREE to monitor pre-existing and new skin pigmentary lesions1

Can IMCIVREE cause skin cancer?

There is no evidence that this change in pigmentation is detrimental to the patient, and no cases of melanoma have been reported.1,3

What were the most common adverse events observed in the clinical trials?

The most common adverse reactions in IMCIVREE-treated patients were hyperpigmentation disorders, injection site reactions, and nausea.

Injection site reactions, nausea, and vomiting tend to occur within the first month after starting treatment, and then diminish over time.4

Changes in skin pigmentation/hair color are primarily reported within the first month of treatment, then become more gradual or stabilize afterward.4

Were any serious treatment-related adverse events observed in clinical studies?

No serious treatment-related adverse reactions were observed in the clinical trial. However, because there is benzyl alcohol preservative in IMCIVREE, there is a risk of serious adverse reactions 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.1

What should a patient do if they think they are or may become pregnant?

Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.1

Can patients take IMCIVREE while breastfeeding? Does IMCIVREE enter the breast milk?

There is no information on the presence of IMCIVREE or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Treatment with IMCIVREE is not recommended while breastfeeding.1

IMCIVREE from multiple-dose vials contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a lactating woman, benzyl alcohol exposure in the breastfed infant is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs.1

What is the mechanism of action?

Setmelanotide is an MC4 receptor agonist with 20-fold less activity at the melanocortin 3 (MC3) and melanocortin 1 (MC1) receptors. MC4 receptors in the brain are involved in regulation of hunger, satiety, and energy expenditure. In patients with obesity due to POMC, PCSK1, and LEPR deficiency associated with insufficient activation of the MC4 receptor, or patients with obesity due to BBS associated with decreased POMC neuronal activity, setmelanotide may re-establish MC4 receptor pathway activity to reduce hunger and promote weight loss through decreased caloric intake and increased energy expenditure. Nonclinical evidence shows that MC4 receptors are important for setmelanotide-regulated appetite and weight loss. The MC1 receptor is expressed on melanocytes, and activation of this receptor leads to accumulation of melanin and increased skin pigmentation independently of ultraviolet light.

How does IMCIVREE work?

IMCIVREE is thought to work by selectively activating melanocortin-4 receptor (MC4R) neurons to restore proper regulation of hunger, energy expenditure, and consequently body weight.1

Have the pivotal studies on IMCIVREE been published?

Yes. The results of these studies have been published in The Lancet Diabetes & Endocrinology. To see the publication, click here.

How were the safety and effectiveness of IMCIVREE evaluated?

The safety and efficacy of IMCIVREE for the treatment of POMC, PCSK1, or LEPR deficiency obesity were established in 2 identically designed, 1-year, open-label studies, each with an 8-week, double-blind withdrawal period.1

To see the full results of the IMCIVREE clinical trials, click here.

Were the patients who did not achieve at least a 5 kg weight loss (or at least 5% weight loss if baseline body weight was <100 kg) at the end of the open-label treatment period included in any analyses? If so, which ones?

Yes. These patients were included in the primary endpoint analysis and safety analyses.1,3

Do patients regain weight after stopping IMCIVREE?

Yes. When treatment with IMCIVREE was withdrawn in patients who had lost weight during the 10-week open-label period, these patients gained an average of 5.5 kg in Study 1 and 5.0 kg in Study 2 over 4 weeks. Reinitiation of treatment with IMCIVREE resulted in subsequent weight loss.1

To see the full results of the IMCIVREE clinical trials, click here.

The package insert mentions skin darkening as a potential reversible side effect. I have read that IMCIVREE may darken hair as well. Is this also a reversible side effect?

Changes in hair color following discontinuation of IMCIVREE have not been studied.

Is there a pharmacologic therapy recommended to manage nausea or vomiting if it were to occur? Are there any therapies for nausea or vomiting that should be avoided?

Treating physicians should manage and mitigate based on their own clinical judgment. No clinical studies evaluating the drug-drug interaction potential of IMCIVREE have been conducted.

How do I prescribe IMCIVREE for my patient(s)?

To prescribe IMCIVREE, a Start Form must be completed. Submit all pages of the completed form via fax to 1-877-805-0130 or email patientsupport@rhythmtx.com.

References: 1. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 2. IMCIVREE [patient information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 3. 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. 4. Data on file. Rhythm Pharmaceuticals, Inc. Boston, MA.

Important Safety Information
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: