CurrentPremera BluecrossPolicy 5.01.606

Hepatitis C Antiviral Therapy

Pharmacy benefit medical policy describing medical necessity, preferred regimens, genotyping and resistance testing, length of therapy, exceptions and documentation requirements for treatment of chronic and acute hepatitis C with direct-acting antivirals and pegylated interferons. Part 1 covers policy criteria, preferred therapies, FDA-approved lengths, genotyping/RAS testing, evidence review, and history/updates through May 12, 2026 / Jun 1, 2026.

Policy Summary

PayerPremera Bluecross

Policy5.01.606 Hepatitis C Antiviral Therapy

Policy CodePolicy 5.01.606

Change TypeRevisions, additions, clarifications (2024–2026)

Effective DateJun 1, 2026

Next Review Date

Key ActionSubmit office visit notes including diagnosis, relevant history, physical evaluation, HCV genotyping, length of requested therapy, and medication history to demonstrate medical necessity.

SourceLink

POLICY UPDATE CHANGES

Policy reorganized into sections including Section 1 (nonindividual formulary plans) and Section 2 (Metallic/individual/small group plans) with separate coverage criteria for certain drugs.

Clarified that non-formulary exception reviews may be approved up to 12 months and that re-authorization is investigational.

Added FDA approved uses for brand sofosbuvir-velpatasvir, brand ledipasvir-sofosbuvir, Sovaldi and Zepatier.

2024 December: Added FDA approved uses for brand sofosbuvir-velpatasvir, brand ledipasvir-sofosbuvir, Sovaldi, and Zepatier; added separate Metallic formulary coverage criteria for multiple DAAs and clarified preferred products in Section 1.

2025 May: Clarified non-formulary exception approvals may be up to 12 months and that re-authorization is investigational; updated policy section formatting and Mavyret criteria to include certain acute HCV treatment.

2026 May: Removed references to previous Section 1, Section 2 (Essentials/HCLV), and Section 3 (Metallic ISHIP) formatting; simplified/updated section references.

2025 September effective change: HCPCS S0145 added for Pegasys to reflect management by both pharmacy and medical benefits (effective 2025-09-05 after 90-day provider notification).

Preferred DAA agents listed

>=90%Typical SVR in trials

12Max non-formulary exception approval duration

InvestigationalRe-authorization status

multipleDAA agents referenced

Coverage Summary

Coverage stance: covered_with_criteria. Scope: Pharmacy benefit medical policy for direct-acting antivirals and pegylated interferons for acute and chronic hepatitis C, including medical necessity criteria, preferred regimens, genotyping/RAS testing, lengths of therapy, exceptions, and documentation requirements. Effective date: Jun. 1, 2026; Last review: May 12, 2026. Preferred DAA agents referenced include: Epclusa, Harvoni, Mavyret, Sovaldi, Vosevi, Zepatier.

Quick facts & thresholds

Viral load threshold for 8-week Harvoni consideration< 6 million IU/mL

Max non-formulary exception duration12 months

Re-authorization statusInvestigational

Typical SVR in trials>=90% (many regimens >95%; Harvoni 8-week 94%, 12-week 99%, 24-week 98%)

Last annual review date (approved)2026-05-12

Initial Therapy Criteria (Medical Necessity)

Medical Necessity - General

Treatment for chronic active hepatitis C may be considered medically necessary per AASLD/IDSA guidance; preferred therapies and resistance exceptions are noted.

General guideline alignment: Treatment aligns with most recent AASLD/IDSA guideline recommendations
Preferred therapy when applicable: Preferred therapy is used when applicable (Epclusa, Harvoni, Mavyret, Sovaldi, Vosevi preferred over other DAA treatments for individuals without cirrhosis or with compensated cirrhosis Child-Pugh A)
Exceptions allowing non-preferred regimens
- RAS indicates preferred combinations unlikely effective: Analysis of resistance-associated substitutions (RASs) indicates that none of the preferred combinations will likely be effective

Continuation Therapy, Exceptions & Non-Preferred Regimens

Non-Preferred / Not Medically Necessary

Non-preferred regimens are generally not covered unless resistance testing or guideline exceptions apply.

Denial condition for non-preferred regimens: Use of other regimens is considered not medically necessary when equally or more effective alternatives at lower cost are available
RAS exception pathway: Non-preferred regimens may be considered medically necessary if resistance (RAS) analysis indicates that preferred combinations are unlikely to be effective; in such cases guideline-recommended regimens may be approved

Investigational/Deviations from Guidelines

Deviations from guideline-recommended therapy length and re-authorization rules.

Pegylated Interferon (Pegasys) & Billing / PA

Pegylated Interferon

Pegylated interferons require prior authorization and have coding/billing implications.

PA requirement: Pegylated interferons (Pegasys, PegIntron) require prior authorization for treatment of chronic hepatitis C in accordance with current guidelines
HCPCS and management note: HCPCS S0145 was added for Pegasys to reflect management by both pharmacy and medical benefits (effective 2025-09-05); providers must bill according to updated management route

Prior Authorization

Prior authorization for pegylated interferon

Applicable Codes

HCPCS (example provided)HCPCS

S0145

Injection, PEGylated interferon alfa-2A (Pegasys), 180 mcg per ml

HCPCS / Pharmacy-medical management notes referencedHCPCS|mixed

S0145

Pegasys added for management by both pharmacy and medical (effective 2025-09-05)

Clinical Evidence

>=90%Typical SVR in trials (SVR12/SVR rates across key DAA trials)

5Preferred DAA agents listed (Epclusa, Harvoni, Mavyret, Sovaldi, Vosevi)

ASTRAL (Epclusa): Phase 3 ASTRAL trials showed a 12‑week SOF/VEL regimen produced very high SVR12 rates — approximately 99% across genotypes in ASTRAL‑1, with similarly high rates in ASTRAL‑2/3; ASTRAL‑4 (decompensated cirrhosis) showed lower SVR without ribavirin and highest SVR (94%) with SOF/VEL + RBV.

POLARIS (Vosevi): POLARIS‑1 and ‑4 demonstrated SOF‑VEL‑VOX achieved SVR12 of 96%–98%, with SVR12 decreasing to 93% in cirrhotic individuals who failed prior NS5A therapy.

GLE/PIB (Mavyret): Phase 2/3 trials of glecaprevir/pibrentasvir reported SVR12 ranging from 89%–100% across studies and populations; 8‑week regimens achieved very high SVR in selected noncirrhotic populations (e.g., 99% in some GT1 trials).

ION (Harvoni): ION trials of ledipasvir/sofosbuvir reported SVR rates of 94% for an 8‑week course in noncirrhotic, treatment‑naïve individuals (with viral load <6 million IU/mL), 99% for 12 weeks, and 98% for 24 weeks.

Background

Hepatitis C is an RNA virus that infects the liver; infection can be acute (sometimes self‑limited) or progress to chronic disease that is often asymptomatic for many years. There are 6 known genotypes (1–6) with >50 subtypes; genotype influences treatment selection and likelihood of achieving sustained virologic response (SVR).

Disease progression: approximately 20%–30% of infected individuals develop cirrhosis within 10–20 years and 5%–10% progress to end‑stage liver disease; after cirrhosis, annual risk of hepatocellular carcinoma is about 1%–4%.

SVR as endpoint: Sustained virologic response (SVR) — clearance of HCV RNA at a defined time after therapy (SVR12/SVR24) — is the primary efficacy endpoint and the current gold standard measure of treatment response; achieving SVR is associated with resolution of liver injury, reduced fibrosis, low relapse risk, and improved outcomes.

Direct‑acting antivirals (DAAs) are orally administered, have shorter courses, fewer side effects, and high SVR rates (>90% in most trials). Recently approved pangenotypic oral agents include examples such as Mavyret, Vosevi, and Epclusa.

Definitions

SVR (Sustained virologic response)Clearance of HCV RNA by qualitative analysis 12 or 24 weeks after therapy cessation (SVR12/SVR24); policy references SVR12 as primary endpoint

RAS (Resistance-associated substitutions)

Revision History

2024-12added

Added FDA approved uses for brand sofosbuvir-velpatasvir, brand ledipasvir-sofosbuvir, Sovaldi (sofosbuvir), and Zepatier (elbasvir-grazoprevir); new Section 2 added with headers and separate Metallic formulary coverage criteria; for Section 1 clarified preferred products (Sovaldi and Vosevi) and Zepatier may be considered for DAA treatment-experienced individuals.

2025-05revised

Clarified that non-formulary exception review authorizations for all drugs may be approved up to 12 months and that re-authorization is investigational; updated policy section formatting (Section 1: Incentive/Open/Select and plans with no pharmacy benefit; Section 2: Essentials; Section 3: Metallic) and updated Mavyret criteria to include certain acute HCV treatment.

2025-09-05added

Policy Summary

PayerPremera Bluecross

Policy5.01.606 Hepatitis C Antiviral Therapy

Policy CodePolicy 5.01.606

Change TypeRevisions, additions, clarifications (2024–2026)

Effective DateJun 1, 2026

Next Review Date

Key ActionSubmit office visit notes including diagnosis, relevant history, physical evaluation, HCV genotyping, length of requested therapy, and medication history to demonstrate medical necessity.

SourceLink

On This Page

Guideline-recommended non-preferred regimens: Guideline-recommended regimen for specific clinical scenarios (e.g., advanced cirrhosis Child-Pugh B/C, transplant setting, special populations)

Preferred Therapies and Indications

Preferred agents and FDA-approved indications/durations; individual agents listed as separate preferred options with key population/duration notes.

Epclusa (sofosbuvir-velpatasvir) - preferred for chronic HCV without cirrhosis or with compensated cirrhosis (Child-Pugh A); FDA-approved 12-week course for adults and pediatric individuals aged 3 years and older for genotypes 1-6; approved for decompensated cirrhosis (B/C) in combination per labeling
Harvoni (ledipasvir-sofosbuvir) - preferred for chronic HCV without cirrhosis or with compensated cirrhosis (Child-Pugh A); FDA approvals include multiple genotype- and population-specific durations (8/12/24 weeks) with specified indications (8-week consideration when viral load < 6 million IU/mL)
Mavyret (glecaprevir-pibrentasvir) - preferred for chronic HCV without cirrhosis or with compensated cirrhosis (Child-Pugh A) and acute HCV without cirrhosis or with compensated cirrhosis; FDA-approved 8-week course for many treatment-naïve adults and pediatric individuals ≥3 years; other durations (12,16 weeks) for specific prior-treatment or genotype/cirrhosis scenarios
Sovaldi (sofosbuvir) - preferred product when used in combination per FDA labeling (various genotype-specific combinations/durations e.g., 12 weeks with peginterferon+ribavirin for genotype 1/4; 12 weeks with ribavirin for genotype 2; 24 weeks with ribavirin for genotype 3)
Vosevi (sofosbuvir-velpatasvir-voxilaprevir) - preferred for certain treatment-experienced individuals; FDA-approved 12-week course for individuals without cirrhosis or with compensated cirrhosis who were previously treated with an NS5A-containing regimen or specific prior sofosbuvir exposure without NS5A
Zepatier (elbasvir-grazoprevir) - may be considered medically necessary for DAA treatment-experienced individuals per guidelines; FDA-approved durations 12 or 16 weeks for genotype 1/4 with stratification by baseline NS5A polymorphisms and prior treatment experience

Genotyping and Resistance Testing

When testing is required to select therapy per guidelines.

HCV genotyping is medically necessary when used according to current guideline recommendations
RAS testing: Genetic testing for resistance-associated substitutions (RASs) is medically necessary to guide selection of DAA regimen when recommended by current guidelines

Prioritization

Prioritization guidance for treatment and high-risk groups.

General prioritization note: Treatment may be prioritized; newer DAA agents show high SVR (>90%) and guideline resources should be consulted for up-to-date prioritization
Advanced cirrhosis guidance: Individuals with more advanced cirrhosis (Child-Pugh B or C) should be treated per current guidelines (ideally in a liver transplant center)

Deviations considered investigational: All deviations from the length of therapy recommended by AASLD/IDSA guidelines are considered investigational

Re-authorization investigational: Re-authorization for all drugs listed in this policy is considered investigational

Denial Risk

Non-preferred regimens denial risk

Use of non-preferred regimens may be considered not medically necessary (and thus denied) when equally or more effective, lower-cost alternatives are available unless analysis of resistance-associated substitutions (RASs) indicates that the preferred regimens will likely be ineffective.

Documentation Required

Re-authorization status

Re-authorization for all drugs listed in this policy is considered investigational and is not routinely approved.

Pegasys and PegIntron require prior authorization for the treatment of chronic hepatitis C in accordance with current guidelines.

Billing Rule

Pharmacy vs medical management for Pegasys

Pegasys (peginterferon alfa-2a) is managed by both the pharmacy and medical benefits effective 2025-09-05; providers must bill according to the updated management route.

HCPCS code S0145 was added effective 2025-09-05

Documentation Required

Medical record documentation required

Submit office visit notes that contain the diagnosis, relevant history, physical evaluation, HCV genotyping, length of requested therapy, and medication history to demonstrate medical necessity.

Documentation Required

Resistance testing when indicated

Order and provide results of resistance-associated substitution (RAS) testing when it is recommended by current guidelines to guide selection of direct-acting antiviral regimens.

Documentation Required

Non-formulary exception duration

Non-formulary exception review authorizations for all drugs listed in this policy may be approved for up to 12 months unless otherwise noted.

Note

Formulary section applicability

Policy section organization was simplified in 2026; previous section labels (Section 1, Section 2, Section 3 for Essentials/Metallic, etc.) were removed. Use the current policy sectioning to determine which formulary rules apply to a member's Rx plan.

Genetic mutations that may affect DAA effectiveness and guide regimen selection

Compensated cirrhosis (Child-Pugh A)Liver cirrhosis with preserved function; agents and durations differ versus decompensated cirrhosis (Child-Pugh B/C)

HCPCS S0145 added for Pegasys to reflect that Pegasys is managed by both pharmacy and medical benefits (effective 2025-09-05 after 90-day provider notification).

2026-05revisedLatest

Removed references to previous Section 1, Section 2 (Essentials/HCLV), and Section 3 (Metallic ISHIP) formatting; simplified/updated policy section references and removed prior section-based plan groupings.

2024-06reviewed

Reviewed prescribing information and AASLD/IDSA guidelines; no changes affecting medical necessity criteria (June 2024 review).