Maralixibat (LUM001) Form

Maralixibat (Livmarli®) is an ileal bile acid transporter inhibitor. FDA Approved Indication(s)
Livmarli is indicated for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older. 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 Livmarli is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Alagille Syndrome (must meet all):

1. Diagnosis of ALGS-associated pruritus confirmed by one of the following (a or b): a. Genetic confirmation with presence of a mutation in JAG1 or NOTCH2; b. Clinical confirmation of both of the following (i and ii): i. Bile duct paucity on liver biopsy;
   ii. Criteria meeting ≥ 3 of the 5 major criteria (see Appendix D);
2. Prescribed by or in consultation with hepatologist or gastroenterologist;
   3. Age ≥ 3 months and ≤ 18 years at therapy initiation;
   4. Pruritus requiring at least moderate scratching (e.g., ≥ 2 on 0-4 scale);
   5. Evidence of cholestasis that is met by ≥ 1 of the following (a – e): a. Total serum bile acid > 3 times upper limit of normal (ULN) for age; b. Conjugated bilirubin > 1 mg/dL; c. Fat-soluble vitamin deficiency otherwise unexplainable; d. Gamma-glutamyl transferase > 3 times ULN for age; e. Intractable pruritus explainable only by liver disease;
3. Failure of ursodeoxycholic acid, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for ursodeoxycholic acid
4. Failure of an agent used for symptomatic relief of pruritus (e.g., antihistamine, rifampin, cholestyramine), unless clinically significant adverse effects are experienced or all are contraindicated;

5. Documentation of member’s current body weight in kilograms;
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   CLINICAL POLICY Maralixibat

6. Dose does not exceed 380 mcg/kg per day, up to a maximum of 28.5 mg (3 mL) per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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. Alagille Syndrome (must meet all):
9. 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);
10. Member is responding positively to therapy as evidenced by an improvement in pruritus;
11. Documentation of member’s current body weight in kilograms;
    4. If request is for a dose increase, new dose does not exceed 380 mcg/kg per day, up to a maximum of 28.5 mg (3 mL) per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

12. 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 Page 2 of 6

    CLINICAL POLICY Maralixibat
    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

13. 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. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALGS: Alagille syndrome FDA: Food and Drug Administration ULN: upper limit of normal Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen ursodeoxycholic acid (Ursodiol®) 10-30 mg/kg/day PO rifampin (Rifadin®) cholestyramine antihistamine Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Off-label 10 mg/kg PO 4-16 g/day PO in 2 divided doses Varies Dose Limit/ Maximum Dose N/A 10 mg/kg/day 16 g/day Varies Appendix C: Contraindications/Boxed Warnings
    None reported Appendix D: Classic Criteria, Based on Five Body Systems, for a Diagnosis of ALGS Classic Criteria
    Liver/cholestasis Usually presenting as jaundice with conjugated hyperbilirubinaemia in Dysmorphic facies the neonatal period, often with pale stools Broad forehead, deep-set eyes, sometimes with upslanting palpebral fissures, prominent ears, straight nose with bulbous tip, and pointed chin giving the face a somewhat triangular appearance Page 3 of 6

    CLINICAL POLICY Maralixibat
    Classic Criteria
    Heart disease Axial skeleton/vertebral anomalies Eye/posterior embryotoxin Most frequently peripheral pulmonary artery stenosis, but also pulmonary atresia, atrial septal defect, ventricular septal defect, and Tetralogy of Fallot Characteristic ‘butterfly’ vertebrae may be seen on an antero-posterior radiograph, and occasionally hemivertebrae, fusion of adjacent vertebrae, and spina bifida occulta Anterior chamber defects, most commonly posterior embryotoxon, which is prominence of Schwalbe’s ring at the junction of the iris and cornea Maximum Dose 380 mcg/kg/day, up to a maximum of 28.5 mg/day (3 mL/day) V. Dosage and Administration
    Indication Dosing Regimen ALGS Starting dose: 190 mcg/kg/day Maintenance: 380 mcg/kg/day Individual dose volume by patient weight Days 1-7 (190 mcg/kg QD) Dosing dispenser size (mL) Patient Weight (kg) 5-6 7-9 10-12 13-15 16-19 20-24 25-29 30-34 35-39 40-49 50-59 60-69 70 or higher Volume QD (mL) 0.1 0.15 0.2 0.3 0.35 0.45 0.5 0.6 0.7 0.9 1 1.25 1.5 0.5 1 3 0.5 Beginning Day 8 (380 mcg/kg QD) Dosing Volume dispenser QD size (mL) (mL) 0.2 0.3 0.45 0.6 0.7 0.9 1 1.25 1.5 1.75 2.25 2.5 1 3 3 VI. Product Availability
    Oral solution: 9.5 mg/mL (30 mL bottle) VII.