MYALEPT, Metreleptin Form

Metreleptin (Myalept®) is a recombinant human leptin analog. FDA Approved Indication(s) Myalept is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Limitation(s) of use:
• The safety and effectiveness of Myalept for the treatment of complications of partial lipodystrophy have not been established.
• The safety and effectiveness of Myalept for the treatment of liver disease, including nonalcoholic steatohepatitis (NASH), have not been established.
• Myalept is not indicated for use in patients with HIV-related lipodystrophy. • Myalept is not indicated for use in patients with metabolic disease, without concurrent evidence of generalized lipodystrophy.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Myalept is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Leptin Deficiency (must meet all):

1. Diagnosis of leptin deficiency as evidenced by baseline leptin level < 12 ng/mL;
   2. Prescribed by or in consultation with an endocrinologist or geneticist;
   3. Age ≥ 1 year;
   4. Member has one of the following (a or b): a. Congenital generalized lipodystrophy (Berardinelli-Seip syndrome) as evidenced by presence of at least one gene mutation (i.e., AGPAT2, BSCL2, CAV1, PTF); b. Acquired generalized lipodystrophy (Lawrence syndrome);

2. Dose does not exceed (a or b):
   a. Body weight ≤ 40 kg: 0.13 mg/kg per day; b. Body weight > 40 kg: 10 mg per day. Approval duration:
   Medicaid/HIM – 6 months
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   CLINICAL POLICY Metreleptin Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Leptin Deficiency (must meet all):
5. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   2. Member is responding positively to therapy;
   3. If request is for a dose increase, new dose does not exceed (a or b): a. Body weight ≤ 40 kg: 0.13 mg/kg per day; b. Body weight > 40 kg: 10 mg per day. Approval duration:
      Medicaid/HIM – 12 months
      Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

6. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: Page 2 of 6

   CLINICAL POLICY Metreleptin CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

7. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents; B. General obesity not associated with congenital leptin deficiency; C. HIV-related lipodystrophy; D. Liver disease, including NASH. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration HIV: human immunodeficiency virus NASH: nonalcoholic steatohepatitis Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o General obesity not associated with congenital leptin deficiency: Myalept has not been shown to be effective in treating general obesity, and the development of anti- metreleptin antibodies with neutralizing activity has been reported in obese patients treated with Myalept o Hypersensitivity to metreleptin • Boxed warning(s): risk of anti-metreleptin antibodies with neutralizing activity and risk of lymphoma o Because of these risks, Myalept is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Myalept REMS Program V. Dosage and Administration
   Indication Complications of leptin deficiency in patients with congenital or acquired Dosing Regimen Weight ≤ 40 kg:
   0.06 to 0.13 mg/kg SC QD (adjust in increments of 0.02 mg/kg) Weight > 40 kg: Maximum Dose Weight ≤ 40 kg: 0.13 mg/kg/day Weight > 40 kg: 10 mg/day Page 3 of 6

   CLINICAL POLICY Metreleptin Indication generalized lipodystrophy Dosing Regimen Males: 2.5 to 10 mg SC QD (adjust in increments of 1.25 to 2.5 mg/day) Females: 5 to 10 mg SC QD (adjust in increments of 1.25 to 2.5 mg/day) Maximum Dose VI. Product Availability
   Lyophilized cake in vial to be reconstituted: 11.3 mg/vial (5 mg/mL after reconstitution)
   VII.