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Imcivree (Setmelanotide) Policy Number: CXXXXX-X

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Imcivree (Setmelanotide) Policy Number: CXXXXX-X Prior Authorization Criteria Imcivree (setmelanotide) Policy Number: CXXXXX-X CRITERIA EFFECTIVE DATES: ORIGINAL EFFECTIVE DATE LAST REVIEWED DATE NEXT REVIEW DUE BY OR BEFORE 05/01/2021 04/2021 04/26/2022 LAST P&T J CODE TYPE OF CRITERIA APPROVAL/VERSION Q2 2021 RxPA 20210428CXXXX-X PRODUCTS AFFECTED: Imcivree (setmelanotide) DRUG CLASS: Anti-Obesity Agents ROUTE OF ADMINISTRATION: Subcutaneous PLACE OF SERVICE: Specialty Pharmacy The recommendation is that medications in this policy will be for pharmacy benefit coverage and patient self-administered AVAILABLE DOSAGE FORMS: Subcutaneous, 1ml multiple-dose vial (10mg/ml) FDA-APPROVED USES: Chronic weight management in adult and pediatric patients 6 years of age and 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 (VUS). COMPENDIAL APPROVED OFF-LABELED USES: None COVERAGE CRITERIA: INITIAL AUTHORIZATION DIAGNOSIS: 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 (VUS) in adult and pediatric patients 6 years of age and older. REQUIRED MEDICAL INFORMATION: A. CHRONIC WEIGHT MANAGEMENT WITH OBESITY DUE TO POMC, PCSK1, or LEPR DEFICIENCY: Molina Healthcare, Inc. confidential and proprietary © 2021 This document contains confidential and proprietary information of Molina Healthcare and cannot be reproduced, distributed, or printed without written permission from Molina Healthcare. This page contains prescription brand name drugs that are trademarks or registered trademarks of pharmaceutical manufacturers that are not affiliated with Molina Healthcare. Page 1 of 4 Prior Authorization Criteria 1. Documented diagnosis of obesity (defined as: Adult patients: BMI of ≥30 kg/m2, Pediatric patients: ≥95th percentile using growth chart assessments) [Documentation of starting weight and BMI required]. AND 2. Documentation of confirmed genetic testing that demonstrates one of the following variants interpreted as pathogenic, likely pathogenic, or of uncertain significance [DOCUMENTATION REQUIRED]: (a) Propiomelanocortin (POMC), (b) Proprotein convertase subtilisin/kexin type 1 (PCSK1) OR (c) Leptin receptor (LEPR) deficiency. NOTE: Imcivree is not indicated for the treatment of members with obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign OR other types of obesity not related to POMC, PCSK1 or LEPR deficiency, including obesity associated with other genetic syndromes and general obesity as Imcivree is not expected to be effective. AND 3. Prescriber attestation that member does not have moderate (eGFR 30-59 mL/min/1.73 m2), severe renal impairment (eGFR 15-29 mL/min/1.73 m2) or end stage renal disease (eGFR less than 15 mL/min/1.73 m2). AND 4. IF member has a history of gastric bypass surgery: the prescriber attests that the member achieved less than 10% of weight loss compared to pre-operative baseline weight OR the member did not maintain weight loss durably from the baseline pre- operative weight. AND 5. Prescriber must attest that the member does not have uncontrolled depression, that the member is not, and the member will be monitored throughout treatment for new onset or worsening depression. DURATION OF APPROVAL: Initial authorization: 4 months, Continuation of Therapy: 1 year QUANTITY: Maximum quantity of 3mg (0.3ml) once daily PRESCRIBER REQUIREMENTS: Prescribed by or in consultation with a geneticist (consultation notes should be provided as documentation at a minimum of annually) AGE RESTRICTIONS: 6 years of age and older CONTINUATION OF THERAPY: 1. Adherence to therapy at least 85% of the time as verified by the prescriber or member medication fill history (Note: Review Rx history for compliance) AND 2. Documentation of member weight loss member of at least 5% of baseline body weight or 5% of baseline body mass index (BMI) for members with continued growth potential [Documentation of body weight and BMI required]. NOTE: 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. AND 3. Prescriber must attest that the member is not actively suicidal or have uncontrolled depression and will continue to be monitored throughout Imcivree treatment AND 4. Documentation of no intolerable adverse effects or drug toxicity Molina Healthcare, Inc. confidential and proprietary © 2021 This document contains confidential and proprietary information of Molina Healthcare and cannot be reproduced, distributed, or printed without written permission from Molina Healthcare. This page contains prescription brand name drugs that are trademarks or registered trademarks of pharmaceutical manufacturers that are not affiliated with Molina Healthcare. Page 2 of 4 Prior Authorization Criteria CONTRAINDICATIONS/EXCLUSIONS/DISCONTINUATION: All other uses of Imcivree (setmelanotide) are considered experimental/investigational and therefore, will follow Molina’s Off- Label policy. No specific contraindications or warnings to Imcivree (setmelanotide) have been identified OTHER SPECIAL CONSIDERATIONS: Dosing: Adult and pediatric patients 12 years of age or older: • Starting dose: 2 mg injected subcutaneously (SC) once daily for 2 weeks. • Monitor patients for gastrointestinal (GI) adverse reactions. If the starting dose is not tolerated, reduce to 1 mg once daily. • If the 1-mg once-daily dose is tolerated and additional weight loss is desired, titrate to 2 mg once daily. • If the 2-mg daily dose is tolerated, increase the dose to 3 mg once daily. • If the 3-mg once-daily dose is not tolerated, maintain administration of 2 mg once daily. Pediatric patients 6–12 years of age: • Starting dose: 1 mg injected SC once daily for 2 weeks. • Monitor patients for GI adverse reactions. If the starting dose is not tolerated, reduce to 0.5 mg once daily. • If the 0.5-mg once-daily dose is tolerated and additional weight loss is desired, titrate to 1 mg once daily. • If the 1-mg dose is tolerated, increase the dose to 2 mg once daily. • If the 2-mg daily dose is not tolerated, reduce to 1 mg once daily. • If the 2-mg once-daily dose is tolerated and additional weight loss is desired, the dose may be increased to 3 mg once daily. Safety/Warnings: Disturbance in sexual arousal: Sexual adverse reactions may occur in patients treated with Imcivree. Spontaneous penile erections in males and sexual adverse reactions in females occurred in clinical studies with Imcivree. Depression and suicidal ideation: Some drugs that target the central nervous system, such as Imcivree, may cause depression or suicidal ideation. Skin pigmentation and darkening of pre-existing nevi: Imcivree may cause generalized increased skin pigmentation and darkening of pre-existing nevi due to its pharmacologic effect. 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. BACKGROUND: Obesity is a very common condition worldwide that has various possible etiologies. There is a growing body of literature that describes rare genetic variants implicated in the melanocortin pathway that cause severe obesity. This pathway consists of neurons that run through the hypothalamus and activate the MC4R and is responsible for regulating hunger and energy expenditure. The POMC-, PCSK1-, and LEPR-expressing neurons are all involved in this pathway. Biallelic variants in POMC, PCSK1, and LEPR are rare genetic disorders that can result in deficiencies that cause obesity. Due to a lack of awareness and overlapping clinical features with other causes of obesity, POMC, PCSK1, and LEPR deficiencies remain underdiagnosed. These conditions may be more obvious in very young children, as the obesity is often extreme and can onset in early infancy. Although there are very few patients currently identified in the United States with these deficiencies (~20), Rhythm Molina Healthcare, Inc. confidential and proprietary © 2021 This document contains confidential and proprietary information of Molina Healthcare and cannot be reproduced, distributed, or printed without written permission from Molina Healthcare. This page contains prescription brand name drugs that are trademarks or registered trademarks of pharmaceutical manufacturers that are not affiliated with Molina Healthcare. Page 3 of 4 Prior Authorization Criteria Pharmaceuticals estimates there may be around 100 to 500 U.S. patients with POMC- or PCSK1- deficiency obesity and around 500 to 2000 U.S. patients with LEPR-deficiency obesity. Patients with these deficiencies suffer from extreme hunger (hyperphagia) and early-onset severe obesity. Additionally, patients with POMC and PCSK1 deficiency can also suffer from adrenal insufficiency, hypothyroidism, and hypogonadism. These patients often have red hair and pale skin, a helpful indication for a provider to test for a genetic variant. Variants in LEPR are associated with
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