Centene Odevixibat (Bylvay) Coverage Update

Coverage Criteria for Odevixibat (Bylvay)

Initial Therapy - PFIC

Covered when ALL of the following are met for genetically confirmed PFIC type 1 or 2:

PFIC initial: 1) Genetic confirmation of PFIC type 1 or 2 (formerly known as Byler disease or syndrome). 2) Pruritus requiring at least medium scratching (ObsRO score ≥ 2). 3) Prescribed by or in consultation with a hepatologist or gastroenterologist. 4) Age ≥ 3 months. 5) No portal hypertension or history of hepatic decompensation. 6) For PFIC type 2, absence of pathologic ABCB11 variants that predict complete absence of the BSEP protein. 7) Failure of ursodeoxycholic acid unless contraindicated or not tolerated. 8) Failure of an agent used for symptomatic relief of pruritus (e.g., antihistamines, rifampin, cholestyramine) unless contraindicated or not tolerated. 9) Documentation of current body weight in kilograms. 10) Dosing follows weight-based regimen starting at 40 mcg/kg/day; if no improvement after 3 months at 40 mcg/kg/day, increase to 80 mcg/kg/day; if no improvement after 3 months at 80 mcg/kg/day, increase to 120 mcg/kg/day. Total daily dose must not exceed approximately 6 mg (6,000 mcg).ObsRO >=2; age >=3 months

Step therapy exception for Illinois HIM per IL HB 5395 effective 1/1/2026.

Initial Therapy - ALGS

Covered when ALL of the following are met for ALGS-associated pruritus:

ALGS initial: 1) Genetic confirmation of ALGS with a pathogenic mutation in JAG1 or NOTCH2 OR clinical confirmation with bile duct paucity on liver biopsy or ≥3 of 5 major clinical criteria. 2) Age ≥ 12 months and < 17 years at therapy initiation. 3) Pruritus requiring at least medium scratching (ObsRO score ≥ 2). 4) Evidence of cholestasis demonstrated by ≥1 of: total serum bile acids > 3× ULN for age; conjugated bilirubin > 1 mg/dL; GGT > 3× ULN for age; unexplained fat‑soluble vitamin deficiency; or intractable pruritus attributable to liver disease. 5) Prescribed by or in consultation with a hepatologist or gastroenterologist. 6) No portal hypertension or history of hepatic decompensation. 7) Failure of ursodeoxycholic acid unless contraindicated or not tolerated. 8) Failure of an agent used for symptomatic relief of pruritus (e.g., antihistamines, rifampin, cholestyramine) unless contraindicated or not tolerated. 9) Documentation of current body weight in kilograms. 10) Dose per ALGS weight-based regimen: recommended 120 mcg/kg PO once daily with a meal (weight-based pellet/capsule counts as provided), not to exceed 120 mcg/kg/day and following product dosing guidance; Bylvay must not be prescribed concurrently with other IBAT inhibitors.ObsRO >=2; age >=12 months and <17 years

Formulation guidance: oral pellets for patients ≤19.5 kg; capsules for patients ≥19.5 kg.

Continuation Therapy

Covered for continuation when ONE of the following is met and additional conditions apply:

Continued therapy: a) Member is currently receiving Bylvay via a Centene benefit; OR b) Member has previously met initial approval criteria. AND the member is responding positively to therapy as evidenced by improvement in pruritus and/or reduction in serum bile acids from baseline; AND documentation of current body weight in kilograms is provided; AND Bylvay is not prescribed concurrently with other IBAT inhibitors. If request is for a dose increase, new dose must not exceed the weight‑based recommended dose/quantity (ALGS: up to 120 mcg/kg/day; PFIC: may escalate to 120 mcg/kg/day) and total daily dose must not exceed ~6 mg (6,000 mcg).improvement in pruritus or reduction in sBA

Approval duration for continued therapy: 12 months.

Other Indications / Off-label

Other indications

Other diagnoses: Coverage for other diagnoses or uses follows applicable formulary, non‑formulary, or off‑label use policies for the member’s line of business (refer to CP.CPA.190, HIM.PA.33, CP.PMN.255, CPCPA.190, HIM.PA.103, CP.PMN.16, CPCPA.09, HIM.PA.154, CP.PMN.53 as applicable). Non‑FDA approved indications not addressed in this policy require sufficient off‑label evidence per referenced policies to be considered for coverage.N/A

Requests lacking sufficient off‑label documentation are not authorized per off‑label use policies.

Initial dosing and escalation rules

Dosing recommendations per indication and weight groups as presented in the document:

ALGS dosing: Recommended dose: 120 mcg/kg PO once daily with a meal. Weight‑based total daily dose and formulation guidance: <7.4 kg = 600 mcg (1 oral pellet); 7.5–12.4 kg = 1,200 mcg (2 oral pellets); 12.5–17.4 kg = 1,800 mcg (3 oral pellets); 17.5–25.4 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). Maximum: 120 mcg/kg/day.max 120 mcg/kg/day

Formulation: oral pellets intended for patients ≤19.5 kg; capsules intended for patients ≥19.5 kg.

PFIC dosing: Recommended starting dose: 40 mcg/kg PO once daily with a meal. If no improvement in pruritus after 3 months, increase by 40 mcg/kg increments to 80 mcg/kg/day, then to 120 mcg/kg/day if needed. Do not exceed a total daily dose of approximately 6 mg (6,000 mcg). Weight‑based pellet/capsule tables apply as provided in dosing tables.max ~6,000 mcg/day

Use pellets for patients ≤19.5 kg and capsules for patients ≥19.5 kg; document current body weight when dosing.

Non‑FDA approved indications that are not specifically addressed by this policy are not authorized unless the provider supplies sufficient documentation of safety and effectiveness in accordance with the applicable off‑label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid).

Odevixibat (Bylvay) is ineffective in PFIC type 2 patients with ABCB11 variants that encode absence of the BSEP protein, because the drug’s mechanism depends on the bile salt export pump pathway. Such patients should not be prescribed Bylvay, and this genetic finding must be considered during authorization decisions.

The policy excludes members with portal hypertension or a history of a hepatic decompensation event from both PFIC and ALGS indications; these clinical exclusions may trigger denial of initial or continued therapy. Additionally, concurrent use with other IBAT inhibitors (e.g., Livmarli) is an exclusion and is not considered medically necessary.

Pathogenic ABCB11 gene variations that predict a complete absence of BSEP protein render Bylvay ineffective; the policy clarifies this exclusion is specific to such variants and should inform coverage determinations for PFIC type 2 patients.

Requests for Bylvay to treat non‑FDA approved indications without sufficient off‑label evidence will be considered not authorized (not medically necessary) unless documentation meeting the referenced off‑label policies is provided.

The policy explicitly states that concurrent administration of Bylvay with other IBAT inhibitors is an exclusion; such concurrent use is considered not medically necessary for both initial and continued therapy and may result in denial.

Provider Actions, Authorization & Documentation Requirements

Prior Authorization

Prior authorization and required evidence

Prior authorization required. Provider must submit documentation (such as office chart notes, laboratory results, genetic testing results, and other clinical information) that supports the member meets all initial or continued therapy approval criteria. Required documentation should include diagnosis, genetic confirmation when applicable, history of prior therapies tried (including failure, intolerance, or contraindication), and current body weight (kg). Continued therapy requests must include documentation of clinical response (e.g., improvement in pruritus, reduction in serum bile acids) and current weight.

Document diagnosis and genetic confirmation (when required).
Include prior therapy history (ursodeoxycholic acid and symptomatic agents) or documentation of contraindication/intolerance.
Provide current body weight in kg.
For continued therapy, provide objective evidence of response (e.g., pruritus improvement, sBA reduction).

Step Therapy

Step therapy requirement

Definitions and Product Details

IBAT inhibitor / Bylvay (Odevixibat)

Drug class & generic nameOdevixibat (Bylvay) is a non-systemic ileal bile acid transport (IBAT) inhibitor that reduces bile acid reabsorption in the ileum.

Mechanism of actionInhibits ileal bile acid transport to lower circulating bile acids and reduce cholestatic pruritus.

PFIC type-specific effectivenessIneffective in PFIC type 2 patients with ABCB11 variants that encode absence of the BSEP protein because Bylvay requires BSEP-mediated bile salt export to produce benefit.

Indications summarizedIndicated for cholestatic pruritus in PFIC (patients ≥3 months) and ALGS (patients ≥12 months) per policy context and prescribing information.

ObsRO pruritus scale

Instrument name

Background

Odevixibat (Bylvay) is a non‑systemic ileal bile acid transport (IBAT) inhibitor available as oral pellets and capsules that reduces bile acid reabsorption in the ileum to lower circulating bile acids. It is indicated to treat cholestatic pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) aged ≥ 3 months and in Alagille syndrome (ALGS) patients aged ≥ 12 months. Because it works by reducing bile acid reuptake, it will not be effective in PFIC type 2 patients who lack the BSEP protein due to certain ABCB11 variants.

Revision History and Policy Changes

2025-09-08addedLatest

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

2025-03-06revised

Clarified exclusion for pathologic ABCB11 variants predicting complete absence of BSEP protein (specific to certain variants) and added exclusion for concurrent use with other IBAT inhibitors for initial and continued therapy.

2025-05-24added

References reviewed and updated and clinical exclusions added for both PFIC and ALGS during annual review; P&T approval recorded.

OpenPayer

Clinical Policy: Odevixibat (Bylvay)

Coverage Criteria for Odevixibat (Bylvay)

Provider Actions, Authorization & Documentation Requirements

Definitions and Product Details

Background

Revision History and Policy Changes