Pharmacy Prior Authorization Criteria

Cholbam (cholic acid)

Indications for Prior Authorization

Cholbam (cholic acid)

• For diagnosis of Bile acid synthesis disorders due to single enzyme defects (SEDs)
  Indicated for the treatment of bile acid synthesis disorders due to single enzyme defects (SEDs).

  Limitation 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.

• For diagnosis of Peroxisomal disorders including Zellweger spectrum disorders
  Indicated for 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 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.

Criteria

Cholbam

Prior Authorization (Initial Authorization)

Length of Approval: 4 Months [F]
For diagnosis of Bile acid synthesis disorders

• Diagnosis of a bile acid synthesis disorder due to a single enzyme defect based on one of the following: [1-6,8,A,B]
• An abnormal urinary bile acid analysis by mass spectrometry
• Molecular genetic testing consistent with the diagnosis
AND
• Prescribed by one of the following: [2,7,E]
• Hepatologist
• Medical geneticist
• Pediatric gastroenterologist
• Other specialist that treats inborn errors of metabolism

Cholbam

Prior Authorization (Initial Authorization)

Length of Approval: 4 Months [F]
For diagnosis of Peroxisomal disorders

• Diagnosis of a peroxisomal disorder based on one of the following: [2-5,8,C,D]
• An abnormal urinary bile acid analysis by mass spectrometry
• Molecular genetic testing consistent with the diagnosis
AND
• Patient exhibits manifestations of at least one of the following: [2-3]
• Liver disease (e.g., jaundice, elevated serum transaminases)
• Steatorrhea
• Complications from decreased fat-soluble vitamin absorption (e.g., poor growth)
AND
• Prescribed by one of the following: [2,7,E]
• Hepatologist
• Medical geneticist
• Pediatric gastroenterologist
• Other specialist that treats inborn errors of metabolism
AND
• Used as adjunctive treatment [2-3]

Cholbam

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Bile acid synthesis disorders or Peroxisomal disorders

• Patient demonstrates positive clinical response to therapy as evidenced by improvement in liver function (e.g., aspartate aminotransferase [AST], alanine aminotransferase [ALT])

P & T Revisions

2024-04-18, 2023-09-13, 2023-04-22, 2022-04-21, 2021-09-27, 2021-05-20, 2020-03-12

References

1. Heubi JE, Setchell KD, Bove KE. Inborn errors of bile acid metabolism. Semin Liver Dis. 2007;27(3):282-94.
2. Cholbam Prescribing Information. Manchester Pharmaceuticals, Inc., San Diego, CA. March 2023.
3. Cholbam Product Monograph. Retrophin, Inc., 2015.
4. Bove KE, Heubi JE, Balistreri WF, Setchell KD. Bile acid synthetic defects and liver disease: a comprehensive review. Pediatr Dev Pathol. 2004;7(4):315-34.
5. Wanders RJA. Peroxisomal disorders. UpToDate web site. https://www.uptodate.com/contents/peroxisomal-disorders?search=cholic%20acid&source=search_result&selectedTitle=2%7E9&usage_type=default&display_rank=1. Updated October 13, 2023. Accessed March 4, 2024.
6. Gonzales E, Gerhardt MF, Fabre M, et al. Oral cholic acid for hereditary defects of primary bile acid synthesis: a safe and effective long-term therapy. Gastroenterology. 2009;137(4):1310-1320.e1-3.
7. Per email with medical geneticist, June 10, 2015.
8. National Organization for Rare Disorders (NORD). Bile acid sythesis disorders. Available at: https://rarediseases.org/rare-diseases/bile-acid-synthesis-disorders/. Accessed February 9, 2023.

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End Notes

1. Congenital deficiencies in the enzymes responsible for catalyzing key reactions in the synthesis of primary bile acids cholic acid and chenodeoxycholic acid are referred to as bile acid synthesis disorders (BASDs) due to single enzyme defects (SEDs). [1] 3 beta-hydroxy-D5-C27-steroid oxidoreductase deficiency (3 beta-HSD) and D4-3-oxosteroid 5 beta-reductase deficiency (AKR1D1 or D4-3-oxo-R), inherited by an autosomal recessive mode, are the most frequent inborn errors of primary bile acid synthesis causing early cirrhosis and liver failure. [6] See Background Table 1 for a list of known bile acid synthesis disorders (BASDs) due to single enzyme defects (SEDs). [1]
2. 2- (or alpha-) methylacyl-CoA racemase (AMACR) deficiency is a deficiency of a single peroxisomal enzyme that may manifest secondary abnormalities of bile acid synthesis; it may thus technically be considered a BASD, as well as, a peroxisomal disorder (PD). [2-5]
3. The spectrum of diseases referred to as peroxisomal disorders (PDs) involve defects in later steps of the bile acid synthetic pathway, such as impaired side-chain oxidation; [3] PDs are therefore classified as either disorders of peroxisome biogenesis (eg, Zellweger syndrome) or deficiencies of a single peroxisomal enzyme (eg, 2- (or alpha-)methylacyl-CoA racemase [AMACR] deficiency). [3] See Background Table 2 for a list of known PDs. [5]
4. Zellweger syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and rhizomelic chondrodysplasia punctata type 1 (RCDP1) are examples of defective biogenesis in which peroxisomes are absent. [4-5] The first 3 disorders are thought to represent a clinical continuum, referred to as Zellweger spectrum disorders (ZSD), with Zellweger syndrome the most severe, infantile Refsum disease the mildest, and neonatal adrenoleukodystrophy intermediate in severity. [5]
5. As per the prescribing information [2], treatment with Cholbam should be initiated and monitored by an experienced hepatologist or pediatric gastroenterologist. At the University of California, San Francisco, medical geneticists see patients with PDs, while specialists in pediatric gastroenterology see patients with BASDs. [7]
6. Cholbam should be discontinued if liver function does not improve within 3 months of starting treatment. [2] An additional month is added to the initial authorization duration to allow for patient follow-up with the provider.

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Revision History

• 2024-04-18: 2024 annual review: no criteria changes. Background updates.
• 2023-09-13: Program update to standard reauthorization language. No changes to clinical intent.
• 2023-04-22: Annual review: no criteria changes.
• 2022-04-21: Annual review: Changed initial approval duration from 12 to 4 months. Added requirements to confirm both diagnoses. Updated reauthorization criteria.
• 2021-09-27: Addition of EHB formulary to guideline, no changes to criteria
• 2021-05-20: Addition of EHB formulary to guideline, no changes to criteria
• 2020-03-12: Annual Review – No Changes

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