ModifiedmhnPolicy CP.PHAR.528

Odevixibat (Bylvay) coverage for PFIC and Alagille syndrome

Defines medical necessity criteria, dosing, and prior authorization requirements for odevixibat (Bylvay) for progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (ALGS) for affected members and prescribing clinicians.

Policy Summary

Payermhn

PolicyOdevixibat (Bylvay) coverage for PFIC and Alagille syndrome

Policy CodePolicy CP.PHAR.528

Change TypeMaterial updates: approval durations revisednew exclusionsALGS indication added

Effective DateJul 20, 2021

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, pruritus severity, labs, genetic results, prior therapy trials, and current weight to support approval.

SourceLink

POLICY UPDATE CHANGES

Revised initial approval durations for both PFIC and ALGS to 12 months.

Added exclusion for concurrent use with other IBAT inhibitors for initial and continued therapy.

Added newly FDA-approved indication for ALGS.

Added step therapy bypass for Illinois HIM per IL HB 5395.

2FDA indications

3Key initial criteria sets

12 monthsApproval duration

6 mg/dayPFIC max dose

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Coverage Criteria for Odevixibat (Bylvay)

Coverage conditions (summary)

Coverage is provided when dosing, exclusions, and prior authorization requirements are met; specific clinical criteria are in other policy sections.

General coverage prerequisites: Member has a diagnosis of PFIC or ALGS appropriate to the indication; prescriber documents absence of portal hypertension or history of hepatic decompensation; for PFIC, member does not have ABCB11 variants predicting complete absence of BSEP protein (PFIC type 2 exclusion); Bylvay is not prescribed concurrently with other IBAT inhibitors.

Exclusions for portal hypertension/hepatic decompensation added 2Q 2024; exclusion for concurrent IBAT inhibitor use and ABCB11 clarification added 2Q 2025.

Dosing constraints: Dosing must follow the weight-based regimen in Section V (examples: body-weight bands mapped to total daily mcg and pellet/capsule quantities); PFIC dosing initiates at 40 mcg/kg/day with possible escalation in 40 mcg/kg increments up to 120 mcg/kg/day not to exceed 6 mg/day; ALGS dosing not to exceed 120 mcg/kg/day per Section V.max 6 mg/day for PFIC

Detailed weight bands and corresponding pellet/capsule quantities are provided in the dosing table (Section V).

Prior authorization and approval duration: Prior authorization is required with documentation supporting that approval criteria are met (diagnosis confirmation, pruritus severity, laboratory results, prior therapy trials or contraindications, specialist involvement, and current weight); initial and continued approval durations have been revised to 12 months for PFIC and ALGS.12 months

Initial approval durations revised in 2Q 2026 annual review; step therapy bypass for Illinois HIM per IL HB 5395 may apply.

Coverage is not authorized for non‑FDA approved indications unless the provider supplies sufficient documentation of efficacy and safety in accordance with the payer's off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace/ICHRA, or CP.PMN.53 for Medicaid) or other evidence of coverage documents.

Requests will be excluded when the member has portal hypertension or a history of hepatic decompensation. These exclusions were added to the policy in the 2Q 2024 annual review and apply to both PFIC and ALGS indications.

Coverage is denied for cases where the member is prescribed odevixibat concurrently with other ileal bile acid transport (IBAT) inhibitors. This exclusion was added for initial and continued therapy in the 2Q 2025 update.

For PFIC type 2, the policy excludes members with pathologic ABCB11 gene variants that predict complete absence of the BSEP protein, because odevixibat acts on bile acid transport and may be ineffective when the bile salt export pump is absent. The 2Q 2025 revisions clarified that this exclusion applies specifically to PFIC type 2.

Bylvay (odevixibat) is contraindicated in patients with prior or active hepatic decompensation events (for example, variceal hemorrhage, ascites, hepatic encephalopathy). Such history or active events preclude use of the medication.

When any of the policy's exclusion conditions are present — including portal hypertension, prior hepatic decompensation, concurrent use of another IBAT inhibitor, or PFIC type 2 with ABCB11 variants predicting absent BSEP — therapy with odevixibat is considered not medically necessary and will not be covered.

Coding and Codes

Therapeutic alternativesmixed

ursodiol (Ursodiol)	Therapeutic alternative listed (dosing 15-30 mg/kg/day; up to 30 mg/kg/day)
antihistamine	Example therapy for pruritus (varies)
rifampin	Example therapy for pruritus (varies)
cholestyramine	Example therapy for pruritus (varies)

Product codes / NDCNDC

NDCs not listed

No NDCs provided in this document portion; refer to Bylvay prescribing information for product NDCs

Serum bile acids (sBA) — threshold

sBA threshold for PFIC initial approval>= 100 µmol/L

Role in criteriaRequired alongside pruritus severity and genetic confirmation for PFIC initial approval

Source contextListed as part of Initial Approval Criteria A.1.b for PFIC

ALGS — sBA and cholestasis evidence (alternate criteria)

ALGS cholestasis evidence — sBA criterionTotal sBA > 3 times upper limit of normal (ULN) for age

Alternate lab/clinical evidenceConjugated bilirubin > 1 mg/dL; GGT > 3x ULN for age; fat‑soluble vitamin deficiency unexplained; or intractable pruritus attributable to liver disease

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required — submit supporting documentation

Prior authorization required. Provider must submit documentation (such as office chart notes, laboratory results, genetic testing reports, weight, prior treatment history, and other clinical information) that supports the diagnosis and that the member meets all approval criteria.

Office chart notes documenting history and severity of pruritus (e.g., ≥ 2 on 0–4 scale)
Lab results including serum bile acids (sBA), bilirubin, GGT, fat‑soluble vitamin levels as applicable
Genetic testing reports (e.g., ABCB11 for PFIC; JAG1 or NOTCH2 for ALGS) or liver biopsy report showing bile duct paucity when clinical confirmation used
Documentation of prior therapies tried and responses (e.g., ursodeoxycholic acid dosing and intolerance/contraindication, agents used for symptomatic pruritus such as antihistamines, rifampin, cholestyramine)
Provider specialty: prescribed by or in consultation with a hepatologist or gastroenterologist
Member age and weight where relevant

Background

Odevixibat (Bylvay) is a non‑systemic ileal bile acid transport (IBAT) inhibitor approved to treat cholestatic pruritus associated with progressive familial intrahepatic cholestasis (PFIC) and, separately, Alagille syndrome (ALGS). It reduces enterohepatic bile acid circulation to alleviate pruritus; however, it may be ineffective in PFIC type 2 patients who have ABCB11 variants that result in absence of the BSEP transporter.

Definitions and Key Terms

IBAT / Odevixibat — short definition

DefinitionOdevixibat (Bylvay) — a non‑systemic ileal bile acid transport (IBAT) inhibitor that reduces enterohepatic circulation of bile acids.

Primary indicationsIndicated for pruritus in PFIC (≥ 3 months) and cholestatic pruritus in ALGS (≥ 12 months).

Mechanism noteActs on the ileal bile acid transporter; may be ineffective when BSEP is absent (certain PFIC type 2 variants).

PFIC and ALGS — brief definitions & diagnostic notes

PFIC — definitionProgressive familial intrahepatic cholestasis (PFIC): genetic cholestatic liver disease including PFIC types 1 and 2 (e.g., ATP8B1, ABCB11 mutations); requires genetic confirmation for coverage of odevixibat.

ALGS — definition

Policy Summary

Payermhn

PolicyOdevixibat (Bylvay) coverage for PFIC and Alagille syndrome

Policy CodePolicy CP.PHAR.528

Change TypeMaterial updates: approval durations revisednew exclusionsALGS indication added

Effective DateJul 20, 2021

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, pruritus severity, labs, genetic results, prior therapy trials, and current weight to support approval.

SourceLink

On This Page

Role in criteriaOne or more of these findings required to meet 'evidence of cholestasis' for ALGS initial approval

Weight-based dosing ranges — body-weight bands and total daily doses

Primary ALGS dosing example (pellets)≤ 7.4 kg = 600 mcg (1 oral pellet); 7.5–12.4 kg = 1,200 mcg (2 pellets); 12.5–17.4 kg = 1,800 mcg (3 pellets)

PFIC initial and step-up regimenStart 40 mcg/kg PO QD; if no improvement after 3 months, may increase by 40 mcg/kg increments to 80 then 120 mcg/kg/day

PFIC maximum total daily doseDo not exceed 6 mg/day (maximum for PFIC)

PFIC capsule weight bands17.5–25.4 kg = 2,400 mcg (2 capsules); 25.5–35.4 kg = 3,600 mcg (3 capsules); 35.5–45.4 kg = 4,800 mcg (4 capsules); 45.5–55.4 kg = 6,000 mcg (5 capsules); ≥55.5 kg = 7,200 mcg (6 capsules)

Documentation Required

Documentation Must Support Diagnosis and Absence of Excluded Conditions

Documentation should explicitly support the documented diagnosis and absence of excluded conditions. Include evidence of genetic confirmation or meet the clinical criteria listed, objective laboratory thresholds, and statements ruling out excluded conditions (e.g., portal hypertension or prior hepatic decompensation).

For PFIC: genetic confirmation of PFIC type 1 or 2 and, for type 2, documentation that ABCB11 variants do not predict complete absence of BSEP protein
For PFIC: sBA ≥ 100 µmol/L and pruritus severity documented
For ALGS: genetic mutation in JAG1 or NOTCH2 OR liver biopsy showing bile duct paucity plus ≥3 major criteria; plus cholestasis evidence (e.g., total sBA >3×ULN, conjugated bilirubin >1 mg/dL, GGT >3×ULN, unexplained fat‑soluble vitamin deficiency, or intractable pruritus)
Document absence of portal hypertension or history of hepatic decompensation (requests may be denied if present)

Step Therapy

Step Therapy Requirements and Illinois HIM Bypass

Step therapy requirements must be documented. Failure of ursodeoxycholic acid is required for both PFIC and ALGS (unless contraindicated or clinically significant adverse effects). For ALGS, failure of an agent used for symptomatic relief of pruritus (e.g., antihistamine, rifampin, cholestyramine) is also required unless contraindicated or intolerant. Illinois HIM requests: step therapy bypass applies per IL HB 5395.

Document trial and failure (or contraindication/intolerance) to ursodeoxycholic acid
For ALGS, document trial and failure (or contraindication/intolerance) of at least one symptomatic pruritus agent (e.g., antihistamine, rifampin, cholestyramine)
Note: Prior authorization may be required for ursodeoxycholic acid in some lines of business
Illinois HIM (IL HB 5395): step therapy requirements do not apply for IL HIM requests as of 1/1/2026

Denial Risk

Denial Triggers and Exclusions — what will lead to denial

Denial triggers — requests may be denied if submitted documentation does not support key required elements or if excluded conditions are present. Providers should ensure objective data and clear documentation are included to avoid denial.

Missing genetic confirmation when required, or insufficient clinical documentation when relying on clinical criteria
Insufficient documentation of pruritus severity (e.g., absence of objective description or scale) or failure to meet sBA thresholds
Evidence of portal hypertension or prior hepatic decompensation (requests may be denied) — added 2Q 2024
Concurrent use with other IBAT inhibitors is not allowed; requests may be denied if concurrent IBAT inhibitor use is present (added 2Q 2025)

Alagille syndrome (ALGS): multisystem disorder; diagnosis by genetic mutation in JAG1 or NOTCH2 or clinical criteria including bile duct paucity plus ≥3 of 5 major criteria.

Diagnostic noteALGS initial approval requires age limits (≥12 months and ≤17 years at initiation) and evidence of cholestasis (see cholestasis criteria).

Concurrent use with other IBAT inhibitors — exclusion

Definition of exclusionConcurrent use with other IBAT inhibitors (e.g., Livmarli®) is an exclusion for both initial and continued therapy; requests may be denied if co‑prescribed.

ScopeApplies to all IBAT inhibitors; added as an exclusion for initial and continued therapy in 2Q 2025.

Provider implicationPrescribers must document that Bylvay is not being used concurrently with any other IBAT inhibitor to meet coverage criteria.

ABCB11 variant exclusion (PFIC type 2) — definition and scope

Definition and scopeABCB11 variant exclusion applies to pathologic variations of the ABCB11 gene that predict complete absence of the BSEP protein (specific to PFIC type 2).

Clinical rationaleBylvay may be ineffective when BSEP is absent because it acts on bile acid transport; therefore PFIC type 2 patients with such variants are excluded.

Policy implicationFor PFIC initial approval, genetic testing must show absence of these specific ABCB11 variants; presence of excluded variants disqualifies coverage.