Patient Selection - POMC, PCSK1, or LEPR Deficiency

• Select patients for treatment with IMCIVREE who have genetically determined or suspected deficiency of POMC, PCSK1, or LEPR [see Clinical Studies (14)].
• Treat patients with variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) in the clinical context of the patient [see Clinical Studies (14)].
• Information on an FDA-approved test for the detection of variants in the POMC, PCSK1, or LEPR is available at http://www.fda.gov/CompanionDiagnostics.

Patient Selection - BBS

Select patients for treatment with IMCIVREE who have a clinical diagnosis of BBS [see Clinical Studies (14)].

Recommended dosage in Adults and Pediatric Patients 12 Years of Age and Older

In adult and pediatric patients 12 years of age and older, the recommended starting dosage is 2 mg (0.2 mL) injected subcutaneously once daily for 2 weeks, and the recommended target dosage is 3 mg (0.3 mL) injected subcutaneously once daily. Monitor patients for gastrointestinal (GI) adverse reactions [see Adverse Reactions (6.1)].

If the starting dosage is:

• Not tolerated, reduce the dosage to 1 mg (0.1 mL) once daily. If the 1 mg once daily dosage is tolerated for at least 1 week, increase the dosage to 2 mg (0.2 mL) once daily.
• Tolerated for 2 weeks, increase the dosage to 3 mg (0.3 mL) once daily. If the 3 mg once daily dosage is not tolerated, decrease the dosage to 2 mg (0.2 mL) once daily.

Recommended Dosage in Pediatric Patients 6 to Less Than 12 Years of Age

In pediatric patients aged 6 to less than 12 years, the recommended starting dosage is 1 mg (0.1 mL) injected subcutaneously once daily for 2 weeks, and the recommended target dosage is 3 mg (0.3 mL) injected subcutaneously once daily. Monitor patients for GI adverse reactions [see Adverse Reactions (6.1)].

If the starting dosage is:

• Not tolerated, reduce the dosage to 0.5 mg (0.05 mL) once daily. If the 0.5 mg once daily dosage is tolerated for at least 1 week, increase the dosage to 1 mg (0.1 mL) once daily.
• Tolerated for 2 weeks, increase the dosage to 2 mg (0.2 mL) once daily. If the 2 mg daily dosage is:
  1. Not tolerated, reduce the dosage to 1 mg (0.1 mL) once daily.
  2. Tolerated, increase the dosage to 3 mg (0.3 mL) once daily.

Recommended Dosage in Patients with Renal Impairment

Recommended Dosage in Patients with End Stage Renal Disease

IMCIVREE is not recommended for use in patients with end stage renal disease (eGFR less than 15 mL/min/1.73 m2).

Recommended Dosage in Patients with Severe Renal Impairment

For adults and pediatric patients 12 years of age and older with severe renal impairment (estimated glomerular filtration rate [eGFR] of 15 to 29 mL/min/1.73 m2), the recommended starting dosage is 0.5 mg (0.05 mL) injected subcutaneously once daily for 2 weeks, and the recommended target dosage is 1.5 mg (0.15 mL) injected subcutaneously once daily [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. Monitor patients for GI adverse reactions [see Adverse Reactions (6.1)].

If the recommended starting dosage is [see Use in Specific Populations (8.6)]:

• Tolerated for 2 weeks, increase the dosage to 1 mg (0.1 mL) once daily. If the 1 mg daily dosage is tolerated for at least 1 week, increase the dosage to 1.5 mg (0.15 mL) once daily.
• Not tolerated, discontinue IMCIVREE.

The use of IMCIVREE in pediatric patients 6 to less than 12 years of age with severe renal impairment is not recommended [see Use in Specific Populations (8.6)].

Recommended Dosage in Patients with Mild or Moderate Renal Impairment

The recommended dosage in patients with mild renal impairment (eGFR of 60 to 89 mL/min/1.73 m2) or moderate renal impairment (eGFR of 30 to 59 mL/min/1.73 m2) is the same as in those with normal kidney function [see Dosage and Administration (2.3, 2.4)].

Recommended Monitoring

Obesity Due to POMC, PCSK1, or LEPR Deficiency

• Periodically assess response to IMCIVREE therapy. In pediatric patients, evaluate the impact of weight loss on growth and maturation.
• Evaluate weight loss after 12-16 weeks of treatment. If a patient has not lost at least 5% of baseline body weight or 5% of baseline BMI for patients with continued growth potential, discontinue IMCIVREE as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

Obesity and a Clinical Diagnosis of BBS

• Periodically assess response to IMCIVREE therapy. In pediatric patients, evaluate the impact of weight loss on growth and maturation.
• Evaluate weight loss after 1 year of treatment. If a patient has not lost at least 5% of baseline body weight or 5% of baseline BMI for patients aged less than 18 years, discontinue IMCIVREE as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

Administration Instructions

• 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.
• Remove IMCIVREE from the refrigerator approximately 15 minutes prior to administration. Alternatively, warm IMCIVREE prior to administration by rolling the vial gently between the palms of the hands for 60 seconds.
• Inspect IMCIVREE visually before use. It should appear clear to slightly opalescent, colorless to slightly yellow. Do not use if particulate matter or discoloration is seen.
• Administer IMCIVREE once daily, at the beginning of the day, without regard to meals.
• Inject IMCIVREE subcutaneously in the abdomen, thigh, or arm, rotating to a different site each day. Do not administer IMCIVREE intravenously or intramuscularly.
• If a dose is missed, resume the once daily regimen as prescribed with the next scheduled dose.