ModifiedPremera BluecrossPolicy N/A

Hepatitis C Antiviral Therapy

Criteria for medical necessity, preferred agents, testing, documentation, and coding for hepatitis C antiviral therapy under the pharmacy benefit; intended for providers requesting coverage. Applies to Premera-managed pharmacy benefit decisions.

Policy Summary

PayerPremera Bluecross

PolicyHepatitis C Antiviral Therapy

Policy CodePolicy N/A

Change TypeModified — material updates to preferred therapies, testing, and authorization rules

Effective DateJun 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and submit documentation (diagnosis, HCV genotype, baseline and on-treatment HCV RNA, therapy length, and medication history); initial approvals may be up to 12 months.

SourceLink

POLICY UPDATE CHANGES

Preferred therapies updated to list Epclusa, Harvoni, Mavyret, Sovaldi, and Vosevi as preferred for chronic HCV without or with compensated cirrhosis.

Genotyping and resistance-associated substitution (RAS) testing are specified as medically necessary when indicated by current guidelines.

Length of authorization and re-authorization statements: initial approvals may be up to 12 months; re-authorization considered investigational.

Added FDA approved uses for brand sofosbuvir-velpatasvir, brand ledipasvir-sofosbuvir, Sovaldi (sofosbuvir) and Zepatier (elbasvir-grazoprevir).

Non-formulary exception review authorizations for all drugs listed may be approved up to 12 months unless otherwise noted; re-authorization for all drugs is considered investigational.

Updated Mavyret (glecaprevir and pibrentasvir) coverage criteria to include treatment for certain individuals with acute hepatitis C across all sections.

Removed references to prior Section structure (Section 1 Open/Preferred/Select, Section 2 Essentials, Section 3 Metallic).

Removed reference to Section 1: Open, Preferred, and Select Formulary Plans and plans with no pharmacy benefit coverage ONLY.

Clarified that non‑formulary exception review authorizations may be approved up to 12 months and that re‑authorization for all drugs listed is considered investigational.

Added HCPC S0145 for Pegasys to be managed by both pharmacy and medical effective September 5, 2025.

Updated Mavyret coverage criteria to include treatment for certain individuals with acute hepatitis C across all sections effective September 1, 2025.

Clarified Section 2 applicability to plans with the High Cost Low Value (HCLV) drug list and removed reference to a Preferred formulary no longer available.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

5preferred DAA products named

>90%SVR rates reported

12wkstypical course

8–16wksMavyret durations

4MAmericans with HCV

SVR >95%typical trial SVR

Coverage Criteria for Hepatitis C Antiviral Therapy

Medical necessity and preferred agent criteria

Covered when criteria below are met and consistent with current AASLD/IDSA guidelines

General coverage: Treatment for chronic active hepatitis C may be considered medically necessary per current AASLD/IDSA guidelines; managed through the pharmacy benefit.

See Preferred Therapies for product selection.

Preferred therapies: Epclusa, Harvoni, Mavyret, Sovaldi, and Vosevi are preferred for chronic HCV without or with compensated cirrhosis (Child-Pugh A).

Mavyret preferred for acute HCV without or with compensated cirrhosis.

Use of non-preferred regimens: Non-preferred regimens are not medically necessary unless RAS analysis indicates preferred combinations will likely be ineffective; deviations from AASLD/IDSA recommended therapy lengths are investigational.

Special guidance provided for treatment-experienced individuals (use Vosevi or Zepatier per guidelines and RASs).

Special populations: Individuals with more advanced cirrhosis (Child-Pugh B or C) should be treated per current guidelines, ideally in a liver transplant center. Treatment-experienced individuals with specific resistance histories have defined options per guidelines.

Some agents require combination with ribavirin for decompensated disease or transplant recipients as specified by FDA labeling.

Genotype and resistance testing

Covered testing when indicated by guidelines

Genotyping: HCV genotyping is medically necessary when used according to current guideline recommendations.

Genotype informs regimen and duration.

RAS testing: Genetic testing for resistance-associated substitutions is medically necessary to guide selection of direct-acting antiviral regimens when recommended by current guidelines.

Supports exceptions to preferred therapy when resistance predicts failure.

Authorization length

Approval periods

Initial authorization for drugs listed may be approved up to 12 months unless otherwise noted.

Re-authorization for all drugs listed is considered investigational.

Product-specific coverage considerations

Coverage aligned with evidence from pivotal trials and guideline-directed indications; product-specific indications and trial efficacy guide regimen selection.

Pangenotypic first-line regimens: SOF/VEL (Epclusa) demonstrated high SVR12 across genotypes in ASTRAL trials (approximately 99% in ASTRAL-1) and is an effective 12-week pangenotypic option for adults and pediatric individuals as indicated by FDA labeling.12-week regimen

Supported by ASTRAL trial results; SVR12 defined as HCV RNA <15 IU/mL at 12 weeks post-treatment.

GLE/PIB (Mavyret) regimen lengths: GLE/PIB (Mavyret) is approved with 8-, 12-, or 16-week regimens depending on prior treatment history and cirrhosis status; trials showed SVR12 ranging ~97%-100% in most populations and support an 8-week option in selected noncirrhotic individuals.8,12,16 weeks depending on population

Trial evidence supports 8-week use in selected noncirrhotic groups.

SOF/VEL/VOX (Vosevi) for DAA-experienced:

Agent-specific clinical evidence and step therapy

Policy references drug-specific criteria and guideline-concordant use; updates across years add or modify agent indications and step therapy.

Trial-defined population and efficacy assessment: C-SALVAGE included genotype 1 treatment-experienced subjects receiving EBR+GZR+RBV for 12 weeks (N=79); SVR12 (HCV RNA SVR12 (HCV RNA < LLOQ at 12 weeks)

Supports clinical effectiveness evidence for Zepatier.

Step therapy conditions added in updates: Step therapy updates were introduced across 2016–2017: requiring Harvoni before Epclusa when clinically appropriate (2016); designating Mavyret first-line where 8- or 12-week courses are adequate (2017); later updating to allow Mavyret, Epclusa, or Harvoni first-line where indicated.agent-specific prior therapy documentation

Prior authorization should reflect these sequencing requirements.

High-level coverage stance and formulary distinctions

Policy affirms coverage of FDA-approved DAA regimens when medical necessity criteria are met and includes formulary-specific criteria.

Formulary and FDA-aligned coverage: Medications listed are subject to the product's FDA dosage and administration prescribing information; certain plan-specific formulary rules apply (e.g., separate coverage criteria for Metallic formulary members).

Section designations and formulary distinctions described in policy history.

Exception and authorization duration: Non-formulary exception review authorizations for drugs listed may be approved up to 12 months unless otherwise noted; re-authorization for listed drugs is considered investigational.

Applies across policy unless specified otherwise.

Preferred versus nonpreferred products: For certain nonindividual formulary plans Sovaldi and Vosevi are indicated as preferred products; Zepatier may be medically necessary for DAA treatment-experienced individuals per AASLD/IDSA guidance.

Plan section determines preferred-agent designations.

Coverage alignment and plan‑specific criteria

Policy aligns coverage and preferred-agent designations with AASLD/IDSA guidelines and FDA approvals; coverage varies by plan section and agent.

Preferred agents and pediatric expansions: Multiple agents (Harvoni, Epclusa, Mavyret, Vosevi, Sovaldi, Zepatier) have had preferred status and pediatric age/weight expansions added per FDA approvals and guideline alignment; check product labeling and policy sections for age/weight-specific indications.

See full policy sections for agent-specific criteria.

Non-formulary exception/authorization: Non-formulary exception review authorizations for listed drugs may be approved up to 12 months unless noted; re-authorization for all drugs is considered investigational.

Effective dates and section restructuring reflected in policy history.

Mavyret acute HCV: Mavyret coverage criteria were updated to include treatment for certain individuals with acute hepatitis C across all sections effective September 1, 2025.

Policy history documents this expansion.

Use of regimens that are not among the policy preferred therapies (e.g., Epclusa, Harvoni, Mavyret, Sovaldi, Vosevi) is considered not medically necessary when equally or more effective preferred options are available at lower cost. An exception may be made when resistance-associated substitution (RAS) testing demonstrates that none of the preferred combinations are likely to be effective; in that case guideline-directed alternative therapy may be considered medically necessary. Providers should document RAS results and the clinical rationale supporting selection of a non-preferred regimen in the prior authorization submission.

Extending DAA treatment beyond the durations recommended by current AASLD/IDSA guidance is not normally advised. Individuals who fail to achieve a sustained virologic response should be evaluated for retreatment with a guideline-appropriate regimen rather than continuation or extension of the original course; requests to extend therapy beyond guideline-recommended durations may be denied absent compelling, guideline-based justification.

Technivie and Daklinza have been removed from the policy references because the manufacturers discontinued these products and they are no longer available. Historical references to these agents were removed during the 2020 policy update.

Initial approvals for the listed antiviral drugs may be granted for up to 12 months where supported by documentation. However, the policy clarifies that re-authorization for all drugs listed in this policy is considered investigational; re-authorization requests should include detailed justification and supporting documentation and will be reviewed under investigational criteria.

The policy history documents multiple prior regimens and changing recommendations over time. Earlier standards (for example, combinations now superseded by DAAs) were at times designated investigational or removed as newer, more effective therapies became available. These historical notes explain prior not-medically-necessary designations and the policy’s evolution in response to guideline and product availability changes.

Deviations from AASLD/IDSA guideline–recommended lengths of therapy are considered investigational and not medically necessary. Specifically, requests that propose therapy durations different from guideline-recommended courses must be supported by guideline-based rationale or will be treated as investigational and may be denied.

When an individual does not achieve an SVR with an initial DAA course, the preferred approach is evaluation for retreatment with an appropriate, guideline-supported regimen rather than simply extending the current treatment. Extending the same course in hopes of eventual SVR is not supported by policy and is not normally advised; retreatment strategies should follow AASLD/IDSA recommendations and be documented for prior authorization consideration.

Historically, the combination of pegylated interferon plus ribavirin was the standard of care but achieved relatively low sustained virologic response rates (approximately 25–27% in transplant populations reported in older literature), and thus is considered inferior to modern DAA regimens. This context is maintained in the policy history as background for understanding the evolution of treatment standards.

Earlier policy language explicitly described certain older regimen combinations as not medically necessary when equally or more effective and lower-cost alternatives were available. For example, combination therapy of simeprevir (Olysio) and sofosbuvir (Sovaldi) was historically identified as not medically necessary in favor of ledipasvir/sofosbuvir (Harvoni) when that alternative was available and preferable by efficacy and cost.

An historical example of a not-medically-necessary entry in the policy is the removal of the SOF/SMV (sofosbuvir + simeprevir) regimen: the policy noted that SOF/SMV ± ribavirin was removed as a recommended regimen and replaced with Harvoni when an equally or more effective and lower-cost option existed.

Coding and Test Metrics

HCPCSHCPCSCovered

S0145

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

Removed HCPCS codes (historical)HCPCS

J9213	HCPCS code referenced as removed
J9214	HCPCS code referenced as removed
S0145	HCPCS code referenced as removed
S0148	HCPCS code referenced as removed

HCPCS added/managedHCPCS

S0145

Pegasys administration code (added to policy management)

HCV RNA and SVR likelihood

HCV RNA threshold associated with higher SVR< 2 million copies/mL (equivalent to ~800,000 IU/mL)

Associated pretreatment factorsLower baseline viral titer (<2 million copies/mL) linked to greater likelihood of SVR

Clinical implicationDocument baseline HCV RNA to inform prognosis and regimen selection

Harvoni 8‑week regimen baseline viral load

Baseline HCV RNA for 8-week Harvoni consideration< 6 million IU/mL

Rationale8‑week Harvoni showed higher relapse when baseline HCV RNA ≥6 million IU/mL (10% relapse observed)

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required

Prior authorization is required for the direct-acting antiviral (DAA) agents listed in this policy. Initial non-formulary exception reviews and other drug reviews may be approved for up to 12 months unless otherwise noted. Re-authorization for drugs listed in this policy is considered investigational and is not routinely approved.

Prior authorization required for listed DAAs and pegylated interferons (e.g., Pegasys HCPCS S0145) — managed per pharmacy & medical rules.
Non-formulary exception reviews may be approved up to 12 months; re-authorization is considered investigational.
Member-specific benefit limits and plan-specific formulary status may affect coverage determinations.

Step Therapy

Step Therapy and Preferred-Agent Sequencing

Step therapy and preferred-agent sequencing apply. Preference is given to specified DAAs (Epclusa, Harvoni, Mavyret, Sovaldi, Vosevi) prior to non-preferred regimens unless resistance-associated substitution (RAS) testing or guideline-based rationale justifies an alternative. Historical step rules have included requirements such as Harvoni before Epclusa or Mavyret first-line where 8- or 12-week courses are adequate; current step requirements follow the latest AASLD/IDSA-aligned policy and may vary by plan/formulary.

Background and Context

Hepatitis C infection may be acute or chronic. Chronic HCV infection is often asymptomatic for many years but can progress to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma if untreated. There are multiple HCV genotypes that influence regimen choice. Modern direct-acting antivirals (DAAs) produce high rates of sustained virologic response (SVR), and SVR (commonly defined as HCV RNA undetectable or below assay lower limit of quantification at 12 weeks post-treatment, SVR12, and historically SVR24) is associated with improved clinical outcomes.

Definitions and Key Terms

SVR (historical definition)

Historical SVR definitionClearance of HCV RNA by qualitative analysis 24 weeks after therapy cessation (SVR24)

Clinical significanceSVR24 is a surrogate endpoint and the historical gold standard measure of treatment response

Relation to outcomesAchievement of SVR associated with reduced hepatic fibrosis and lower relapse risk

Resistance-associated substitutions (RASs)

DefinitionResistance-associated substitutions (RASs) are genetic resistance mutations in HCV

Testing indicationRAS testing is medically necessary when recommended by current guidelines to guide DAA selection

Policy Summary

PayerPremera Bluecross

PolicyHepatitis C Antiviral Therapy

Policy CodePolicy N/A

Change TypeModified — material updates to preferred therapies, testing, and authorization rules

Effective DateJun 1, 2026

Next Review DateN/A

SourceLink

On This Page

SOF/VEL/VOX (Vosevi) achieved SVR12 of 96%-98% in POLARIS trials and is indicated for certain DAA-experienced individuals (including those with prior NS5A inhibitor failure); a 12-week course is the approved duration and an 8-week regimen is not approved.

12-week regimen generally

SVR12 decreased in cirrhotics who failed NS5A therapy.

Ledipasvir/Sofosbuvir (Harvoni) selection: Harvoni demonstrated high SVR across 8-, 12-, and 24-week regimens; an 8-week regimen may be considered only in treatment-naïve individuals with baseline HCV RNA <6,000,000 IU/mL due to higher relapse with higher viral loads.baseline HCV RNA <6,000,000 IU/mL for 8-week consideration

12- and 24-week regimens are effective; ribavirin addition did not improve efficacy while increasing adverse events.

Zepatier (Elbasvir/Grazoprevir) use: Zepatier showed efficacy in genotype 1 and 4 populations in trials using 12-week (and select 16-week) regimens; SVR12 was measured with assays having LLOQ typically 15 IU/mL (one trial 25 IU/mL).12-week regimen typical

Includes trials in special populations such as HIV coinfection and those with renal impairment.

Action for providersConfirm baseline HCV RNA <6,000,000 IU/mL before requesting an 8‑week Harvoni course

Lower limit of quantification (LLOQ) in trials

Typical trial LLOQ used15 IU/mL (COBAS AmpliPrep/COBAS Taqman HCV test v2.0)

Exception in one trialC‑SCAPE trial used LLOQ = 25 IU/mL

InterpretationSVR endpoints in pivotal trials defined using assay-specific LLOQ (commonly 15 IU/mL)

Proteinuria threshold reference

Proteinuria threshold for cryoglobulinemia-related criteria>2 grams urinary protein per 24 hours

Policy useSpecified as a medical necessity criterion in historical policy wording

DocumentationProvide 24‑hour urine protein quantification when applicable to support coverage decisions

Preferred-agent sequencing: Epclusa, Harvoni, Mavyret, Sovaldi, Vosevi are preferred for chronic HCV without cirrhosis or with compensated cirrhosis (Child-Pugh A).
DAA-experienced sequencing: Vosevi or Zepatier may be used for certain DAA-experienced patients per AASLD/IDSA guidance and RAS considerations.
Non-preferred regimens are considered not medically necessary unless RAS testing indicates preferred agents are unlikely to be effective.

Note

Individual Review for Special Populations

Certain populations and clinical scenarios require individual clinical review. Post-transplant patients, individuals awaiting transplant, those with HIV and/or hepatitis B coinfection, decompensated cirrhosis, end-stage renal disease, pediatric patients, and other complex cases will be evaluated on an individual basis and approved in accordance with current guideline recommendations.

Treatment for post-transplant or pre-transplant individuals approved per current AASLD/IDSA guidelines; consult hcvguidelines.org.
HIV/HBV coinfection, decompensated cirrhosis, ESRD, and pediatric cases require individualized review and guideline-based decision-making.
Zepatier may be considered for select DAA-experienced individuals per guidelines and resistance testing.

Documentation Required

Documentation and Virologic Baseline Requirements

Providers must document virologic testing and baseline clinical factors to support medical necessity. Records should include pretreatment and on-treatment HCV RNA measurements, genotype/RAS testing when relevant, and other baseline factors associated with SVR.

Documentation: office visit notes with diagnosis, history, physical exam, HCV genotyping (and RAS testing when applicable), requested therapy length, and comprehensive medication history.
Virologic testing: baseline HCV RNA and on-treatment HCV RNA results; define SVR per policy (SVR12/SVR24) and monitor early virologic response (EVR).
Clinical trial assay note: trials used COBAS AmpliPrep/COBAS Taqman v2.0 with LLOQ typically 15 IU/mL (one trial 25 IU/mL).

Note

Extended Treatment Not Normally Advised

Extended treatment beyond recommended durations is not normally advised. Individuals who fail to achieve sustained virologic response (SVR) should be evaluated for retreatment with a guideline-appropriate regimen rather than lengthening the current course.

Do not extend therapy beyond guideline-recommended durations; assess for retreatment options if SVR is not achieved.

Denial Risk

Formulary, Benefit Verification, and Denial Risk

Formulary-specific coverage rules and benefit limitations may result in denial if requirements are not met. Providers should verify member benefits and plan formulary status prior to prescribing.

Formulary-specific coverage: Some plans (e.g., Metallic/individual ISHIP formularies) have separate criteria and preferred product lists; nonpreferred use without an approved exception may be denied.
Benefit verification: Always consult the member benefit booklet or contact member services to determine coverage limits and pharmacy benefit details.
Non-formulary exception denials may occur if plan criteria (including step therapy or RAS-based justification) are not satisfied.

Identifies resistance that may warrant alternative or nonpreferred regimens

SVR and SVR12 (definitions)

SVR (general) and SVR12SVR commonly defined as HCV RNA < LLOQ at designated post‑treatment timepoints (e.g., SVR12 = undetectable HCV RNA at 12 weeks post‑treatment)

Trial endpointMany pivotal trials used SVR12 (HCV RNA <15 IU/mL at 12 weeks) as primary efficacy endpoint

Documentation recommendedRecord HCV RNA and assay LLOQ when reporting SVR results

Early virologic response (EVR)

Definition of EVRClearance of HCV RNA during the first 12 weeks of therapy

Partial response≥2‑log decrease in viral load after 12 weeks defines a partial response

Clinical useEVR helps assess on‑treatment response and may inform retreatment decisions

SVR12

SVR12 definitionHCV RNA less than the assay lower limit of quantification at 12 weeks after treatment cessation (SVR12)

Use in trialsPrimary efficacy endpoint for many Phase‑3 trials (e.g., ASTRAL series) and used to report cure rates

Assay dependenceSVR12 interpretation depends on the assay LLOQ used in the study or clinical test

Lower limit of quantification (LLOQ)

LLOQ conceptAssay-specific minimum HCV RNA level that can be reliably quantified (commonly 15 IU/mL in trials)

Examples from trialsCOBAS AmpliPrep/COBAS Taqman v2.0 LLOQ = 15 IU/mL; C‑SCAPE trial assay LLOQ = 25 IU/mL

ImplicationReport the assay and its LLOQ when documenting virologic outcomes

DAA (abbreviation)

AbbreviationDAA = direct-acting antiviral

DescriptionOral antiviral agents targeting HCV proteins with high SVR rates and generally fewer side effects than interferon-based regimens

ExamplesIncludes agents such as Epclusa, Harvoni, Mavyret, Sovaldi, Vosevi, Zepatier

Direct-acting antivirals (DAAs)

Term expansionDirect-acting antivirals (DAAs)

Clinical rolePangenotypic and genotype-directed oral therapies that form the mainstay of contemporary HCV treatment

Policy relevancePreferred DAA products are listed in policy and subject to prior authorization per formulary rules