Setmelanotide

Select patients for treatment who have a clinical diagnosis of BBS or who have genetically determined or suspected deficiency of POMC, PCSK1, or LEPR. Recommended starting dosage injected subcutaneously for: Adults and pediatric patients aged 12 years and older is 2 mg (0.2 mL) once daily for 2 weeks. Pediatric patients aged 6 to less than 12 years is 1 mg (0.1 mL) once daily for 2 weeks. Pediatric patients aged 2 to less than 6 years is 0.5 mg (0.05 mL) once daily for 2 weeks. Recommended maintenance

dosage for adults and pediatric patients aged 6 years and older is 3 mg (0.3 mL) injected subcutaneously once daily. ( 2.2 , 2.3 ) Recommended maintenance dose for pediatric patients aged 2 to less than 6 years is determined by body weight. For recommended dosage in patients with renal impairment, see Full Prescribing Information. For titration and administration recommendations, see Full Prescribing Information. ( 2.2 , 2.3 , 2.4 , 2.5 , 2.6 ) 2.1 Patient Selection BBS Select patients for treatment with IMCIVREE who have a clinical diagnosis of BBS . Consider genetic confirmation in pediatric patients aged <6 years. POMC, PCSK1, or LEPR Deficiency Select patients for treatment with IMCIVREE who have genetically determined or suspected deficiency of POMC, PCSK1, or LEPR . 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 . 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. 2.2

Recommended Dosage in Adults and Pediatric Patients Aged 12 Years and Older The recommended starting dosage is 2 mg (0.2 mL) injected subcutaneously once daily for 2 weeks in adults and pediatric patients aged 12 years and older. Monitor patients for gastrointestinal (GI) adverse reactions during dosage initiation and titration . 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. The recommended maintenance dosage is 3 mg (0.3 mL) injected subcutaneously once daily. 2.3

Recommended Dosage in Adults and Pediatric Patients Aged 2 Years and Older with End Stage Renal Disease [estimated glomerular filtration (eGFR) less than 15 mL/min/1.73 m 2 ] IMCIVREE is not recommended for use in patients with end stage renal disease. Recommended Dosage in Patients with Severe Renal Impairment (eGFR of 15 to 29 mL/min/1.73 m 2 ) Adults and Pediatric Patients Aged 12 Years and Older The recommended starting dosage is 0.5 mg (0.05 mL) injected subcutaneously once daily for 2 weeks in adults and pediatric patients aged 12 years and older with severe renal impairment. Monitor patients for GI adverse reactions during dosage initiation and titration . If the recommended starting dosage is : Not tolerated, discontinue IMCIVREE. 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. The recommended maintenance dosage is 1.5 mg (0.15 mL) injected subcutaneously once daily .

Recommended Dosage in Adults and Pediatric Patients Aged 2 Years and Older with Mild (eGFR of 60 to 89 mL/min/1.73 m 2 ) or Moderate (eGFR of 30 to 59 mL/min/1.73 m 2 ) Renal Impairment The recommended dosage in patients with mild or moderate renal impairment is the same as in those with normal kidney function [see( 2.2 , 2.3 , 2.4 )] . 2.6 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-gauge 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.

Recommended Dosage 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 in pediatric patients aged 6 to less than 12 years. Monitor patients for GI adverse reactions during dosage initiation and titration . 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: Not tolerated, reduce the dosage to 1 mg (0.1 mL) once daily. Tolerated, increase the dosage to 3 mg (0.3 mL) once daily. The recommended maintenance dosage is 3 mg (0.3 mL) injected subcutaneously once daily. 2.4

Recommended Dosage in Pediatric Patients Aged 2 to Less Than 6 Years The recommended starting dosage is 0.5 mg (0.05 mL) injected subcutaneously once daily for 2 weeks in pediatric patients aged 2 to less than 6 years. Monitor patients for GI adverse reactions during dosage initiation and titration . If the starting dosage is: Not tolerated, discontinue the product. Tolerated for 2 weeks, increase the dosage based on baseline body weight, as presented in Table 1 . Table 1:Recommended Maintenance Dosage Based on Baseline Body Weight in Pediatric Patients Aged 2 to Less Than 6 Years Patient Weight/Treatment Week Daily Dose Volume to be Injected 15 kg to less than 20 kg Week 1 and onward 0.5 mg once daily 0.05 mL once daily 20 kg to less than 30 kg Weeks 1‑2 0.5 mg once daily 0.05 mL once daily Week 3 and onward 1 mg once daily 0.1 mL once daily 30 kg to less than 40 kg Weeks 1‑2 0.5 mg once daily 0.05 mL once daily Weeks 3‑4 1 mg once daily 0.1 mL once daily Week 5 and onward 1.5 mg once daily 0.15 mL once daily Greater than or equal to 40 kg Weeks 1‑2 0.5 mg once daily 0.05 mL once daily Weeks 3‑4 1 mg once daily 0.1 mL once daily Weeks 5‑6 1.5 mg once daily 0.15 mL once daily Weeks...