Odevixibat (A4250) Form

Odevixibat (Bylvay™) is a non-systemic ileal bile acid transport inhibitor. FDA Approved Indication(s) Bylvay is indicated for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC). Limitation(s) of use: Bylvay may not be effective in PFIC type 2 patients with ABCB11 variants resulting in non-functional or complete absence of bile salt export pump protein (BSEP-3). 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 Bylvay is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Progressive Familial Intrahepatic Cholestasis (must meet all):

1. Diagnosis of genetically confirmed PFIC type 1 or 2 (formerly known as Byler disease or syndrome) with presence of both of the following (a and b): a. Pruritus requiring at least medium scratching (e.g., ≥ 2 on 0 to 4 scale); b. Serum bile acids ≥ 100 µmol/L;
2. Prescribed by or in consultation with a hepatologist or gastroenterologist;
   3. Age ≥ 3 months;
   4. Member does not have pathologic variations of the ABCB11 gene that predict complete absence of the BSEP protein;
3. Failure of ursodeoxycholic acid, unless clinically significant adverse effects are experienced or contraindicated;
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 weight in kg;

   8. Dose does not exceed one of the following (a, b, or c): a. 40 mcg/kg per day, not to exceed the recommended dose and quantity by body weight as outlined in Section V; Page 1 of 7

   CLINICAL POLICY Odevixibat b. 80 mcg/kg per day (up to a maximum of 6 mg per day), and documentation supports no improvement in pruritus after 3 months at a dose of 40 mcg/kg per day; c. 120 mcg/kg per day (up to a maximum of 6 mg per day), and documentation supports no improvement in pruritus after 3 months at a dose of 80 mcg/kg per day. Approval duration: 6 months 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: 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.
   II. Continued Therapy A. Progressive Familial Intrahepatic Cholestasis (must meet all):
8. 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);

9. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: a. Improvement in pruritus; b. Reduction of serum bile acids from baseline;

   3. Documentation of member’s current weight in kg;
   4. If request is for a dose increase, new dose does not exceed one of the following (a, b, or c):
      a. 40 mcg/kg per day, not to exceed the recommended dose and quantity by body weight as outlined in Section V; b. 80 mcg/kg per day (up to a maximum of 6 mg per day), and documentation supports no improvement in pruritus after 3 months at a dose of 40 mcg/kg per day; Page 2 of 7

   CLINICAL POLICY Odevixibat c. 120 mcg/kg per day (up to a maximum of 6 mg per day), and documentation supports no improvement in pruritus after 3 months at a dose of 80 mcg/kg per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

10. 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

11. 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 ABCB11: ATP binding cassette subfamily B member 11 BSEP-3: bile salt export pump 3 FDA: Food and Drug Administration IBAT: ileal bile acid transporter ObsRO: observer-reported outcome PFIC: progressive familial intrahepatic 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 Dose Limit/ Maximum Dose 30 mg/kg/day Varies ursodeoxycholic acid (Ursodiol®)* Example of therapies for pruritus: antihistamine, rifampin, cholestyramine 15-30 mg/kg/day Varies Page 3 of 7

    CLINICAL POLICY Odevixibat 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 Appendix C: Contraindications/Boxed Warnings
    None reported Appendix D: General Information
    • Initial care for patients with PFIC targets symptoms and nutritional problems, including fat-soluble vitamin supplementation.
    • Off-label conventional treatment for PFIC pruritus includes antihistamines, rifampin, and cholestyramine. In the pivotal PEDFIC 1 study, 85% of placebo and 57.1% of Bylvay patients were already receiving rifampicin. • Ursodiol is usually considered first line therapy for all PFIC types and has been proven to improve liver function and pruritus. Use of Ursodiol is supported by expert opinion; additionally, in the pivotal PEDFIC 1 study, 90% of placebo and 76.2% of Bylvay patients were already receiving Ursodiol.
    • Other PFIC options include surgical options such as nasobiliary drainage, partial external biliary diversion, and liver transplant. • The PEDFIC 1 study only enrolled patients with PFIC type 1 or 2. PEDFIC 2 is an ongoing open-label extension of PEDFIC 1 and includes patients with other types of PFIC; however, results are not yet available.
    • Bylvay will not work on PFIC type 2 with ABCB11 variants that encode for absence of BSEP-3 since Bylvay acts on the bile acid transporter. Therefore, in patients missing the BSEP-3 transporter, Bylvay may not inhibit the bile salt export pump.
    Appendix E: Observer-Reported Outcome (ObsRO) Instrument for Pruritus
    • Used to measure patients’ scratching as observed by their caregiver twice daily (once in the morning and once in the evening) • Scratching was assessed on a 5-point scale (0-4): o 0: no scratching o 1: a little scratching o 2: medium scratching
    o 3: a lot of scratching o 4: worst possible scratching Appendix F: Genetic Confirmation of PFIC • PFIC 1 o Protein deficiency: FIC1 o Mutated gene: ATP8B1 • PFIC 2
    o Protein deficiency: BSEP o Mutated gene: ABCB11 Page 4 of 7

    CLINICAL POLICY Odevixibat V. Dosage and Administration Indication Dosing Regimen PFIC The recommended dose is 40 mcg/kg PO AM with a meal. If there is no improvement in pruritus after 3 months, the dosage may be increased in 40 mcg/kg increments up to 120 mcg/kg PO QD not to exceed a total daily dose of 6 mg.
    Maximum Dose 6 mg/day Bylvay oral pellets are intended for use by patients weighing < 19.5 kg, while the capsules are intended for use by patients weighing ≥ 19.5 kg. Recommended dosage/quantity for 40 mcg/kg/day: Total daily dose (mcg) Body weight (kg) 200 (1 oral pellet) ≤ 7.4 400 (2 oral pellets) 7.5 to 12.4 600 (3 oral pellets) 12.5 to 17.4 800 (2 capsules) 17.5 to 25.4 1,200 (1 capsule) 25.5 to 35.4 1,600 (2 capsules) 35.5 to 45.4 2,000 (3 capsules) 45.5 to 55.4 2,400 (2 capsules) ≥ 55.5 VI. Product Availability • Oral pellets: 200 mcg, 600 mcg • Capsules: 400 mcg, 1,200 mcg VII.