• Imcivree is a prescription medicine used in adults and children 6 years of age and older with obesity due to:
  • The genetic conditions proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency, to help them lose weight and keep the weight off.
  • Bardet-Biedl syndrome (BBS) to help them lose weight and keep the weight off.
• Your healthcare provider should order a genetic test to confirm POMC, PCSK1, or LEPR deficiency before you start treatment.
• Imcivree is not for use in people with the following conditions because it may not work:
  • Obesity due to suspected POMC, PCSK1, or LEPR deficiency not confirmed by genetic testing or with benign or likely benign testing results.
  • Other types of obesity not related to POMC, PCSK1, or LEPR deficiency, or BBS, including obesity associated with other genetic conditions and general obesity.

It is not known if this medicine is safe and effective in children under 6 years of age.

• See the detailed Instructions for Use that comes with your prescription to learn how to prepare and inject Imcivree.
• Imcivree is given as an injection under your skin (subcutaneous) by you or a caregiver.
• A healthcare provider should show you or your caregiver how to prepare and inject your dose of Imcivree before injecting for the first time. Do not try to inject Imcivree unless you have been trained by a healthcare provider.
• Use Imcivree exactly as prescribed by your healthcare provider.
• Your healthcare provider may tell you to stop using Imcivree if you have not lost a certain amount of weight after 12 to 16 weeks of treatment.
• If you have BBS, hour healthcare provider may tell you to stop using Imcivree if you have not lost a certain amount of weight after 1 year of treatment.
• Imcivree should be injected 1 time each day when you first wake up. Imcivree can be given with or without food.
• If you miss a dose, inject your next dose at the regularly scheduled time the next day.

Usual Adult Dose for Obesity:

Initial dose: 2 mg subcutaneously once a day for 2 weeks
-If tolerated and additional weight loss is desired: Increase to 3 mg subcutaneously once a day
-If not tolerated: Reduce to 1 mg subcutaneously once a day; if additional weight loss is desired, titrate to 2 mg subcutaneously once a day
Maintenance dose: 1 to 3 mg per day
Maximum dose: 3 mg per day

Comments:
-To assess tolerability, monitor for gastrointestinal adverse reactions.
-Evaluate weight loss after 12 to 16 weeks of treatment in patients with POMC-, PCSK1-, or LEPR-deficiency or after 1 year in patients with BBS; if patient has not lost at least 5% of baseline body weight, it is unlikely they will achieve and sustain clinically meaningful weight loss with continued treatment.
-Available tests for the detection of POMC, PCSK1, or LEPR variants have not been approved or cleared by the FDA.
-This drug is not for the treatment of patients with obesity due to suspected POMC, PCKS1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign or other types of obesity unrelated to POMC, PCSK1, or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity as it is not expected to be effective.

Use: For chronic weight management in patients with obesity due to proopiomelanocortin (POMC), proprotein convertase/subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance; and Bardet-Biedl syndrome (BBS).

Usual Pediatric Dose for Obesity:

6 to less than 12 years:
Initial dose: 1 mg subcutaneously once a day for 2 weeks
-If tolerated and additional weight loss is desired: Increase to 2 mg subcutaneously once a day
-If not tolerated: Reduce to 0.5 mg subcutaneously once a day; if additional weight loss is desired, titrate to 3 mg subcutaneously once a day
Maintenance dose: 0.5 to 3 mg per day
Maximum dose: 3 mg per day

12 years or older:
Initial dose: 2 mg subcutaneously once a day for 2 weeks
-If tolerated and additional weight loss is desired: Increase to 3 mg subcutaneously once a day
-If not tolerated: Reduce to 1 mg subcutaneously once a day; if additional weight loss is desired, titrate to 2 mg subcutaneously once a day
Maintenance dose: 1 to 3 mg per day
Maximum dose: 3 mg per day

Comments:
-To assess tolerability, monitor for gastrointestinal adverse reactions.
-Evaluate weight loss after 12 to 16 weeks of treatment in patients with POMC-, PCSK1-, or LEPR-deficiency or after 1 year in patients with BBS; if patient has not lost at least 5% of baseline body weight (or 5% of baseline BMI for patients with continued growth potential) it is unlikely they will achieve and sustain clinically meaningful weight loss with continued treatment.
-Available tests for the detection of POMC, PCSK1, or LEPR variants have not been approved or cleared by the FDA.
-This drug is not for the treatment of patients with obesity due to suspected POMC, PCKS1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign or other types of obesity unrelated to POMC, PCSK1, or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity as it is not expected to be effective.

Use: For chronic weight management in patients 6 years or older with obesity due to proopiomelanocortin (POMC), proprotein convertase/subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance; and Bardet-Biedl syndrome (BBS).

Before you start treatment, tell your healthcare provider about all your medical conditions, including if you:

• have or have had areas of darkened skin, including skin discoloration (hyperpigmentation).
• have or have had depression, or suicidal thoughts or behavior.
• have kidney problems.
• are pregnant or planning to become pregnant. Losing weight while pregnant may harm your unborn baby. Your healthcare provider may stop your treatment if you become pregnant. Tell your healthcare provider if you become pregnant or think you might be pregnant during treatment.
• are breastfeeding or plan to breastfeed. It is not known if Imcivree passes into your breastmilk. You should not breastfeed during treatment.

Imcivree may cause serious side effects, including:

• Male and female sexual function problems. Imcivree can cause an erection that happens without any sexual activity in males (spontaneous penile erection) and unwanted sexual reactions (changes in sexual arousal that happen without any sexual activity) in females. If you have an erection lasting longer than 4 hours, get emergency medical help right away.
• Depression and suicidal thoughts or actions. You or a caregiver should call your healthcare provider right away if you have any new or worsening symptoms of depression.
• Increased skin pigmentation and darkening of skin lesions (moles or nevi) you already have. These changes happen because of how Imcivree works in the body and will go away when you stop using Imcivree. You should have a full body skin exam before starting and during treatment to check for skin changes.
• Benzyl alcohol toxicity. Benzyl alcohol is a preservative in Imcivree. Benzyl alcohol can cause serious side effects, including death, in premature and low-birth weight infants, who have received medicines that contain benzyl alcohol. Imcivree should not be used in premature and low-birth weight infants.

The most common side effects of include:

• injection site reactions
• darkening of the skin
• nausea
• vomiting
• headache
• erection that happens without any sexual activity in males
• diarrhea
• stomach pain.

These are not all the possible side effects.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or Rhythm Pharmaceuticals at 1-833-789-6337.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Imcivree has low potential for drug interactions.

How should I use Imcivree?

• See the detailed Instructions for Use that comes with your prescription to learn how to prepare and inject Imcivree.
• Imcivree is given as an injection under your skin (subcutaneous) by you or a caregiver.
• A healthcare provider should show you or your caregiver how to prepare and inject your dose of Imcivree before injecting for the first time. Do not try to inject Imcivree unless you have been trained by a healthcare provider.
• Use Imcivree exactly as prescribed by your healthcare provider.
• Your healthcare provider may tell you to stop using Imcivree if you have not lost a certain amount of weight after 12 to 16 weeks of treatment.
• If you have BBS, hour healthcare provider may tell you to stop using Imcivree if you have not lost a certain amount of weight after 1 year of treatment.
• Imcivree should be injected 1 time each day when you first wake up. Imcivree can be given with or without food.
• If you miss a dose, inject your next dose at the regularly scheduled time the next day.

Dosing information

Usual Adult Dose for Obesity:

Initial dose: 2 mg subcutaneously once a day for 2 weeks
-If tolerated and additional weight loss is desired: Increase to 3 mg subcutaneously once a day
-If not tolerated: Reduce to 1 mg subcutaneously once a day; if additional weight loss is desired, titrate to 2 mg subcutaneously once a day
Maintenance dose: 1 to 3 mg per day
Maximum dose: 3 mg per day

Comments:
-To assess tolerability, monitor for gastrointestinal adverse reactions.
-Evaluate weight loss after 12 to 16 weeks of treatment in patients with POMC-, PCSK1-, or LEPR-deficiency or after 1 year in patients with BBS; if patient has not lost at least 5% of baseline body weight, it is unlikely they will achieve and sustain clinically meaningful weight loss with continued treatment.
-Available tests for the detection of POMC, PCSK1, or LEPR variants have not been approved or cleared by the FDA.
-This drug is not for the treatment of patients with obesity due to suspected POMC, PCKS1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign or other types of obesity unrelated to POMC, PCSK1, or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity as it is not expected to be effective.

Use: For chronic weight management in patients with obesity due to proopiomelanocortin (POMC), proprotein convertase/subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance; and Bardet-Biedl syndrome (BBS).

Usual Pediatric Dose for Obesity:

6 to less than 12 years:
Initial dose: 1 mg subcutaneously once a day for 2 weeks
-If tolerated and additional weight loss is desired: Increase to 2 mg subcutaneously once a day
-If not tolerated: Reduce to 0.5 mg subcutaneously once a day; if additional weight loss is desired, titrate to 3 mg subcutaneously once a day
Maintenance dose: 0.5 to 3 mg per day
Maximum dose: 3 mg per day

12 years or older:
Initial dose: 2 mg subcutaneously once a day for 2 weeks
-If tolerated and additional weight loss is desired: Increase to 3 mg subcutaneously once a day
-If not tolerated: Reduce to 1 mg subcutaneously once a day; if additional weight loss is desired, titrate to 2 mg subcutaneously once a day
Maintenance dose: 1 to 3 mg per day
Maximum dose: 3 mg per day

Comments:
-To assess tolerability, monitor for gastrointestinal adverse reactions.
-Evaluate weight loss after 12 to 16 weeks of treatment in patients with POMC-, PCSK1-, or LEPR-deficiency or after 1 year in patients with BBS; if patient has not lost at least 5% of baseline body weight (or 5% of baseline BMI for patients with continued growth potential) it is unlikely they will achieve and sustain clinically meaningful weight loss with continued treatment.
-Available tests for the detection of POMC, PCSK1, or LEPR variants have not been approved or cleared by the FDA.
-This drug is not for the treatment of patients with obesity due to suspected POMC, PCKS1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign or other types of obesity unrelated to POMC, PCSK1, or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity as it is not expected to be effective.

Use: For chronic weight management in patients 6 years or older with obesity due to proopiomelanocortin (POMC), proprotein convertase/subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance; and Bardet-Biedl syndrome (BBS).