Pharmacy Prior Authorization Criteria

Livmarli (maralixibat) - PA, NF

Indications for Prior Authorization

Livmarli (maralixibat)

• For diagnosis of Alagille syndrome
  Indicated for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 3 months of age and older.

• For diagnosis of Progressive Familial Intrahepatic Cholestasis (PFIC)
  Indicated for the treatment of cholestatic pruritus in patients 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC).

  Limitations of use: LIVMARLI is not recommended in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in non-functional or complete absence of bile salt export pump (BSEP) protein.

Criteria

Livmarli

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Alagille syndrome

• Both of the following:
• Diagnosis of Alagille Syndrome (ALGS)
AND
• Molecular genetic testing confirms mutations in the JAG1 or NOTCH2 gene [A, 2, 6]
AND
• Documentation of ONE of the following: [4]
• Total serum bile acid > 3x the upper limit of normal (ULN)
• Conjugated bilirubin > 1 mg/dL
• Fat soluble vitamin deficiency otherwise unexplainable
• Gammaglutamyl transpeptidase (GGT) > 3x ULN
AND
• Patient is experiencing moderate to severe cholestatic pruritus [4]
AND
• Patient has had an inadequate response to at least two of the following treatments used for the relief of pruritus: [B, 2, 7]
• Ursodeoxycholic acid (e.g., Ursodiol)
• Antihistamines (e.g., diphenhydramine, hydroxyzine)
• Rifampin
• Bile acid sequestrants (e.g., Questran, Colestid, Welchol)
AND
• Patient is 3 months of age or older
AND
• Prescribed by or in consultation with a hepatologist or gastroenterologist

Livmarli

Non Formulary

Length of Approval: 12 Month(s)
For diagnosis of Alagille syndrome

• Submission of medical records (e.g., chart notes) confirming both of the following:
• Diagnosis of Alagille Syndrome (ALGS)
AND
• Molecular genetic testing confirms mutations in the JAG1 or NOTCH2 gene [A, 2, 6]
AND
• Submission of medical records (e.g., chart notes) confirming ONE of the following: [4]
• Total serum bile acid > 3x the upper limit of normal (ULN)
• Conjugated bilirubin > 1 mg/dL
• Fat soluble vitamin deficiency otherwise unexplainable
• Gammaglutamyl transpeptidase (GGT) > 3x ULN
AND
• Patient is experiencing moderate to severe cholestatic pruritus [4]
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming patient has had an inadequate response to at least two of the following treatments used for the relief of pruritus: [B, 2, 7]
• Ursodeoxycholic acid (e.g., Ursodiol)
• Antihistamines (e.g., diphenhydramine, hydroxyzine)
• Rifampin
• Bile acid sequestrants (e.g., Questran, Colestid, Welchol)
AND
• Patient is 3 months of age or older
AND
• Prescribed by or in consultation with a hepatologist or gastroenterologist

Livmarli

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Progressive Familial Intrahepatic Cholestasis (PFIC)

• Both of the following:
• Diagnosis of Progressive familial intrahepatic cholestasis (PFIC)
AND
• Molecular genetic testing confirms mutations in the ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, or MYO5B gene [9]
AND
• Patient is experiencing both of the following:
• Moderate to severe pruritus
• Patient has a serum bile acid concentration above the upper limit of the normal reference for the reporting laboratory
AND
• Patient is 12 months of age or older
AND
• Patient has had an inadequate response to at least two of the following treatments used for the relief of pruritus:
• Ursodeoxycholic acid (e.g., Ursodiol)
• Antihistamines (e.g., diphenhydramine, hydroxyzine)
• Rifampin
• Bile acid sequestrants (e.g., Questran, Colestid, Welchol)
AND
• Prescribed by or in consultation with one of the following:
• Hepatologist
• Gastroenterologist

Livmarli

Non Formulary

Length of Approval: 12 Month(s)
For diagnosis of Progressive Familial Intrahepatic Cholestasis (PFIC)

• Submission of medical records (e.g., chart notes) confirming both of the following:
• Diagnosis of Progressive familial intrahepatic cholestasis (PFIC)
AND
• Molecular genetic testing confirms mutations in the ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, or MYO5B gene [9]
AND
• Patient is experiencing both of the following:
• Moderate to severe pruritus
• Submission of medical records (e.g., chart notes) confirming patient has a serum bile acid concentration above the upper limit of the normal reference for the reporting laboratory
AND
• Patient is 12 months of age or older
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming patient has had an inadequate response to at least two of the following treatments used for the relief of pruritus:
• Ursodeoxycholic acid (e.g., Ursodiol)
• Antihistamines (e.g., diphenhydramine, hydroxyzine)
• Rifampin
• Bile acid sequestrants (e.g., Questran, Colestid, Welchol)
AND
• Prescribed by or in consultation with one of the following:
• Hepatologist
• Gastroenterologist

Livmarli

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of All indications listed above

• Patient demonstrates positive clinical response to therapy (e.g., reduced serum bile acids, improved pruritus)

P & T Revisions

2024-11-15, 2024-09-06, 2024-05-02, 2023-12-13, 2023-10-03, 2023-03-31, 2022-11-01, 2022-07-28, 2022-03-01, 2021-11-11

References

1. Livmarli Prescribing Information. Mirum Pharmaceuticals, Inc. Foster City, CA. July 2024.
2. Ayoub MD, Kamath BM. Alagille Syndrome: Diagnostic Challenges and Advances in Management. Diagnostics (Basel). 2020;10(11):907. Published 2020 Nov 6. doi:10.3390/diagnostics10110907
3. Saleh M, Kamath BM, Chitayat D. Alagille syndrome: clinical perspectives. Appl Clin Genet. 2016;9:75-82. Published 2016 Jun 30. doi:10.2147/TACG.S86420
4. ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/study/NCT02160782 Accessed October 18, 2021.
5. Emerick KM, Elias MS, Melin-Aldana H, et al. Bile composition in Alagille Syndrome and PFIC patients having Partial External Biliary Diversion. BMC Gastroenterol. 2008;8:47. Published 2008 Oct 20. doi:10.1186/1471-230X-8-47
6. Diaz-Frias J, Kondamudi NP. Alagille Syndrome. [Updated 2021 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507827/
7. Shneider BL, Spino C, Kamath BM, et al. Placebo-Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome. Hepatol Commun. 2018;2(10):1184-1198.
8. www.albireopharma.com/patients-families/progressive-familial-intrahepatic-cholestasis-pfic. Accessed April 15, 2024.
9. Protocol: MRX-502. https://cdn.clinicaltrials.gov/large-docs/30/NCT03905330/Prot_000.pdf. Accessed April 16, 2024.

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End Notes

1. Alagille Syndrome is an autosomal dominant disease with variable expressivity, caused by heterozygous mutations in either JAG1 or NOTCH2. The vast majority of cases are due to JAG1 mutations accounting for 94%, and NOTCH2 mutations in additional 2–4%. [2]
2. The management of pruritus in ALGS is challenging, and a variety of therapies are often used. These include antihistamines, rifampin, ursodeoxycholic acid, cholestyramine, naltrexone, and sertraline. Clinical experience suggests that these drugs have variable efficacy in reducing pruritus; however, no prospective clinical trials has quantified the effect of any of these therapies, either alone or in combination. [7]
3. Diagnostic testing may include liver functions tests, liver ultrasound and biopsy, and/or bile analysis. Genetic testing may be used in selected patients to confirm diagnosis and distinguish type. All 3 subtypes of PFIC have increased serum bile acid levels. [8]

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Revision History

• 2024-11-15: 2024 Annual Review - no changes
• 2024-09-06: Updated age criterion for PFIC and new GPI
• 2024-05-02: Addition of new PA and NF PFIC criteria
• 2023-12-13: 2023 Annual Review - addition of gastroenterologist
• 2023-10-03: Program update to standard reauthorization language. No changes to clinical intent
• 2023-03-31: Update to age criteria
• 2022-11-01: 2022 Annual Review - no changes
• 2022-07-28: Updated guideline name to include - PA, NF
• 2022-03-01: Update to add NF criteria
• 2021-11-11: New program

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