CHOLBAM, Cholic Acid Form

Cholic acid (Cholbam®) is a bile acid. FDA Approved Indication(s) Cholbam is indicated for: • Treatment of bile acid synthesis disorders due to single enzyme defects (SEDs) • Adjunctive treatment of peroxisomal disorders (PDs) including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat-soluble vitamin absorption Limitation(s) of use: The safety and effectiveness of Cholbam on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established.
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 Cholbam is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Bile Acid Synthesis Disorders or Peroxisomal Disorders (must meet all):

1. Diagnosis of one of the following (a or b): a. Bile acid synthesis disorders due to SEDs; b. PDs, including Zellweger spectrum disorders;
2. Diagnosis is confirmed by at least one of the following (a or b): a. An abnormal urinary bile acid consistent with a bile acid synthesis or Zellweger spectrum disorder as confirmed by fast atom bombardment ionization – mass spectrometry (FAB-MS) analysis; b. Molecular genetic testing consistent with diagnosis (e.g., biallelic pathogenic variants in ABCD3, AKR1D1, AMACR, HSD3B7, CYP27A1, CYP7B, or PEX genes);
3. Prescribed by or in consultation with a hepatologist, gastroenterologist, or metabolic disease specialist;

4. Documentation of current (within the last 30 days) liver function test results;

   5. Dose does not exceed 17 mg/kg per day. Page 1 of 6

   CLINICAL POLICY Cholic Acid Approval duration: 3 months B. Other diagnoses/indications (must meet 1 or 2):

5. 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
6. 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. Bile Acid Synthesis Disorders or Peroxisomal Disorders (must meet all):
7. 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);
8. Member is responding positively to therapy as evidenced by improvement in liver function tests with both of the following (a and b): a. Alanine transaminase (ALT) or aspartate transaminase (AST) values reduced to < 50 U/L or baseline levels reduced by 80%; b. Total bilirubin values reduced to ≤ 1 mg/dL;
9. If request is for a dose increase, new dose does not exceed 17 mg/kg per day.
   Approval duration:
   Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less 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 Page 2 of 6

    CLINICAL POLICY Cholic Acid 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.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FAB-MS: fast atom bombardment ionization – mass spectrometry FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives Not applicable Appendix C: Contraindications/Boxed Warnings None reported PDs: peroxisomal disorders SEDs: single enzyme defects
    Appendix D: General Information • Bile acid synthesis disorders and PDs may be diagnosed with either genetic testing or urine bile acid profile by FAB-MS. Bile acid testing by FAB-MS assesses the phenotypic, biochemical response to a genetic disorder.
    • Treatment should be initiated and monitored by a hepatologist, gastroenterologist, or metabolic disease specialist. • Discontinue Cholbam if liver function does not improve within 3 months of starting treatment or complete biliary obstruction develops. • Discontinue treatment with Cholbam at any time if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis. • The safety and effectiveness of Cholbam on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established. V. Dosage and Administration
    Indication Bile acid synthesis disorders due to SED, Dosing Regimen 10 to 15 mg/kg/day administered PO in one or two divided doses Maximum Dose 17 mg/kg/day Page 3 of 6

    CLINICAL POLICY Cholic Acid Indication PD including Zellweger spectrum disorders Dosing Regimen Maximum Dose For concomitant familial hypertriglyceridemia: 11 to 17 mg/kg/day PO in one or two divided doses VI. Product Availability
    Capsules: 50 mg, 250 mg VII.