Subject: Livmarli 5005-A SGM P2024
Policy:
I. INDICATIONS
The indications below including FDA-approved indications and compendial uses are
considered a covered benefit provided that all the approval criteria are met and the member
has no exclusions to the prescribed therapy.
FDA-Approved Indications
A. Treatment of cholestatic pruritus in patients 3 months of age and older with Alagille
syndrome (ALGS).
B. 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.
All other indications are considered experimental/investigational and not medically necessary.
II. DOCUMENTATION
Submission of the following information is necessary to initiate the prior authorization review:
A. Initial requests: Genetic testing results confirming a diagnosis of Alagille syndrome (ALGS)
or progressive familial intrahepatic cholestasis (PFIC), if applicable.
B. Continuation requests: Chart notes or medical record documentation showing benefit from
therapy (e.g., improvement in pruritus).
III. EXCLUSIONS
Coverage will not be provided for members who have PFIC type 2 with variants in the ABCB11
gene resulting in non-functional or complete absence of the bile salt export pump (BSEP)
protein.
IV. PRESCRIBER SPECIALTIES
This medication must be prescribed by or in consultation with a hepatologist or
gastroenterologist.
V. CRITERIA FOR INITIAL APPROVAL
A. Cholestatic pruritus in Alagille syndrome (ALGS)
Authorization of 6 months may be granted for treatment of cholestatic pruritus in Alagille
syndrome (ALGS) when all of the following criteria are met:
1. Member has a diagnosis of ALGS established by one of the following (see Appendix for
major clinical features of ALGS):
i. Genetic testing (e.g., mutations in JAG1, NOTCH2)
ii. Family history of ALGS and one or more major clinical features of ALGS
iii. Bile duct paucity and three or more major clinical features of ALGS
iv. Four or more major clinical features of ALGS
2. Member has evidence of cholestasis (e.g., elevated serum bile acid level).
3. Member does not have a history or presence of other concomitant liver disease (e.g.,
biliary atresia, progressive familial intrahepatic cholestasis [PFIC], liver cancer).
4. Member has not received a liver transplant.
5. Member is 3 months of age or older.
B. Pruritus in progressive familial intrahepatic cholestasis (PFIC)Authorization of 6
months may be granted for treatment of pruritus in progressive familial intrahepatic
cholestasis (PFIC) when all of the following criteria are met:
1. Member has a confirmed molecular diagnosis of PFIC (e.g., mutations in ATP8B1,
ABCB11, ABCB4, TJP2, MYO5B).
2. Member has evidence of cholestasis (e.g., elevated serum bile acid level).
3. Member does not have any other concomitant liver disease (e.g., biliary atresia, liver
cancer, alternate non-PFIC related etiology of cholestasis).
4. Member has not received a liver transplant.
5. Member is 12 months of age or older.
VI. CONTINUATION OF THERAPY
Authorization of 12 months may be granted for all members (including new members)
requesting continuation of therapy when the member is experiencing benefit from therapy (e.g.,
improvement in pruritus).
VII. OTHER
Member cannot use the requested medication concomitantly with any other ileal bile acid
transporter (IBAT) inhibitor (e.g., Bylvay).
VIII. APPENDIX
Major clinical features of ALGS
1. Hepatic abnormality (e.g., cholestasis)
2. Cardiac abnormality (e.g., stenosis of the peripheral pulmonary artery and its branches)
3. Skeletal abnormality (e.g., butterfly vertebrae)
4. Ophthalmologic abnormality (e.g., posterior embryotoxon)
5. Characteristic facial features (e.g., triangular-shaped face with a broad forehead and a
pointed chin, bulbous tip of the nose, deeply set eyes, and hypertelorism)
6. Vascular abnormalities (e.g., intracranial bleeds, systemic vascular anomalies)
7. Renal structural or functional abnormality (e.g., abnormally small size, cysts)
Place of Service:
Outpatient
The above policy is based on the following references:
- Livmarli [package insert]. Foster City, CA: Mirum Pharmaceuticals, Inc.; July 2024.
- Spinner NB, Gilbert MA, Loomes KM, et al. Alagille syndrome. GeneReviews® [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK1273/#__NBK1273_dtls__. Published May 19, 2000. Last updated January 4, 2024. Accessed August 14, 2024.
- Menon J, Shanmugam N, Vij M, et al. Multidisciplinary management of Alagille syndrome. J Multidiscip Healthc. 2022;15:353-364.
- National Organization for Rare Disorders (NORD). Alagille syndrome. Rare Disease Database. https://org. Published 2020. Last updated January 30, 2024. Accessed August 14, 2024.
- The Childhood Liver Disease Research Network. Alagille syndrome. https://childrennetwork.org/For-Physicians/Alagille-Syndrome-Information-for-Physicians. Accessed August 14, 2024.
- The Childhood Liver Disease Research Network. Progressive familial intrahepatic cholestasis. https://childrennetwork.org/Clinical-Studies/Progressive-Familial-Intrahepatic-Cholestasis. Accessed August 14, 2024.
- McKiernan P, Bernabeu JQ, Girard M, et al. Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis. JHEP Rep. 2023;6(1):1000949. doi: 10.1016/j.jhepr.2023.100949
Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
December 04, 2024
