Obeticholic Acid (Ocaliva) Form

Obeticholic acid (Ocaliva®) is a farnesoid X receptor agonist. FDA Approved Indication(s) Ocaliva is indicated for the treatment of: • Primary biliary cholangitis (PBC) (without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension) either in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA*

• This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
  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 Ocaliva is medically necessary when the following criteria are met:
  I. Initial Approval Criteria
  A. Primary Biliary Cholangitis (must meet all):

  1. Diagnosis of PBC;
  2. Prescribed by or in consultation with a hepatologist or gastroenterologist;
  3. Age ≥ 18 years;
  4. One of the following (a or b):
     a. Member does not have cirrhosis;
     b. Member has compensated cirrhosis without evidence of portal hypertension (e.g., ascites, gastroesophageal varices, or persistent thrombocytopenia);
  5. Failure (as evidenced by sustained elevation in ALP ≥ 1.67 times the upper limit of normal) of ≥ 12 month trial of UDCA (ursodiol) at a dose of ≥ 13 mg/kg/day, unless contraindicated or clinically significant adverse effects are experienced;
  6. Prescribed in combination with UDCA, unless contraindicated or clinically significant adverse effects are experienced;
  7. Dose does not exceed 10 mg (1 tablet) per day. Approval duration: 6 months Page 1 of 7

  CLINICAL POLICY
  Obeticholic acid B. Other diagnosis/indications (must meet 1 or 2):

  1. 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
  2. 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. Primary Biliary Cholangitis (must meet all):
  3. 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);
  4. Member is responding positively to therapy as evidenced by one of the following (a or b): a. Initial reauthorization: reduction in ALP level from pretreatment level; b. Subsequent reauthorization: continued reduction or maintenance of initial reduction in ALP level;
  5. If request is for a dose increase, new dose does not exceed 10 mg (1 tablet) per day. Approval duration: 12 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 Page 2 of 7

  CLINICAL POLICY
  Obeticholic 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

  2. 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 AASLD: American Association for the Study of Liver Diseases
     ALP: alkaline phosphatase
     FDA: Food and Drug Administration PBC: primary biliary cholangitis UDCA: ursodeoxycholic acid 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 ursodiol (Urso®, Urso Forte®, Actigall®) 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. 13-15 mg/kg/day PO in 2-4 divided doses Dose Limit/ Maximum Dose 15 mg/kg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
     o Decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event. o Compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia). o Complete biliary obstruction. • Boxed warning(s):
     o Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with Ocaliva treatment in PBC patients with either compensated or decompensated cirrhosis. Page 3 of 7

  CLINICAL POLICY
  Obeticholic acid o Ocaliva is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension. o Permanently discontinue Ocaliva in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension; or experience clinically significant hepatic adverse reactions while on treatment. Appendix D: General Information • According to the AASLD Primary Biliary Cirrhosis 2018 practice guidelines, UDCA dosed at 13-15 mg/kg/day orally is recommended for all patients with PBC who have abnormal liver enzyme values regardless of histological stage. Improvement in liver tests will be seen within a matter of a few weeks and 90% of the improvement usually occurs within 6-9 months. The eligibility criteria in the Ocaliva efficacy trial required enrolled patients to have a minimum 12 month history of taking UDCA. In the PBC clinical trial, response was defined as a composite of three criteria: ALP less than 1.67-times the ULN, total bilirubin less than or equal to ULN, and an ALP decrease of at least 15%. The ULN for ALP was defined as 118 U/L for females and 124 U/L for males. The ULN for total bilirubin was defined as 1.1 mg/dL for females and 1.5 mg/dL for males. • • A diagnosis of PBC can be established when two of the following three criteria are met:
  o Alkaline phosphatase (ALP) is elevated above the upper limit of normal as defined by normal laboratory references values;
  o Positive anti-mitochondrial antibodies (AMA) or other PBC-specific auto-antibodies, including sp100 or gp210, if AMA is negative;
  o Histologic evidence of PBC from a liver biopsy;
  V. Dosage and Administration
  Indication PBC Dosing Regimen 5 mg PO QD titrated after 3 months to 10 mg PO QD based on efficacy and tolerability Maximum Dose 10 mg/day VI. Product Availability
  Tablets: 5 mg, 10 mg
  VII.