CurrentPremera BluecrossPolicy 5.01.606

Hepatitis C Antiviral Therapy

Pharmacy-managed policy defining medical necessity, preferred therapies, exceptions, prior authorization and documentation requirements for direct-acting antiviral (DAA) treatment of acute and chronic hepatitis C across multiple formulary plan types. Includes drug-specific FDA-approved treatment durations, indications by genotype and cirrhosis status, and use of genotyping/RAS testing.

Policy Summary

PayerPremera Bluecross

PolicyHepatitis C Antiviral Therapy

Policy CodePolicy 5.01.606

Change TypeFDA indications, section reorganization, coverage clarifications

Effective DateMay 1, 2025

Next Review DateN/A

Key ActionSubmit office visit notes documenting diagnosis, genotyping, requested therapy length, medication history and supporting documentation to demonstrate medical necessity.

SourceLink

POLICY UPDATE CHANGES

Added FDA approved uses for brand sofosbuvir-velpatasvir; brand ledipasvir-sofosbuvir; Sovaldi; and Zepatier (Dec 2024 / Jan 2025 updates).

Policy reorganized to reflect current AASLD/IDSA recommendations and multiple updates over years including addition of Zepatier, step therapy updates, and pediatric indication expansions.

Clarified that non-formulary exception review authorizations for all drugs listed in this policy may be approved up to 12 months unless otherwise noted; re-authorization for all drugs listed in this policy is considered investigational.

Added HCPCS S0145 for Pegasys due to management change.

Updated Mavyret coverage to include treatment for certain individuals with acute hepatitis C across all sections.

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Coverage Summary

Overview: This pharmacy-managed coverage policy (Policy 5.01.606, Effective 5, 2025; Last Revised 12, 2025) defines medical necessity, preferred therapies, prior authorization, documentation requirements and plan-section specific coverage rules for direct-acting antiviral (DAA) treatment of both acute and chronic hepatitis C across three formulary sections (Section 1: Incentive/Open/Select and plans with no pharmacy benefit; Section 2: Essentials formulary; Section 3: Metallic/Individual/Small Group/Student ISHIP). The policy states that treatment decisions follow current AASLD/IDSA guideline recommendations and the FDA-approved dosing and durations for each product; deviations from guideline-recommended lengths of therapy are considered investigational.

Key thresholds and quick facts

Maximum Initial Authorization MonthsUp to 12 months (non-formulary exception duration / max initial authorization months)

FDA-Recognized Genotypes CoveredGenotypes 1-6

Formulary Sections Defined3 (Section 1, Section 2, Section 3)

Policy aligns with AASLD/IDSA guidelinesYes — treatment follows current AASLD/IDSA guideline recommendations

Medical-Necessity Criteria

General Medical Necessity

Covered when ALL of the following are met, consistent with current AASLD/IDSA guidance and FDA labeling:

ALL of the following

Diagnosis of chronic active hepatitis C virus (HCV) infection confirmed by detectable HCV RNA.
Therapy selection is consistent with the most recent AASLD/IDSA treatment guidelines and the US FDA-approved prescribing information for the chosen regimen.
Prescriber is a clinician experienced in the management of hepatitis C (e.g., hepatologist, infectious disease specialist, gastroenterologist, or other clinician following guideline recommendations).
Operational: if prescriber is not a specialist, documentation must show coordination with or consult to a specialist.
For individuals with decompensated cirrhosis (Child-Pugh B or C), treatment is in accordance with current guideline recommendations and ideally coordinated with a liver transplant center.

Step Therapy and Preferred Agent Rules

Pediatric indication updates: The policy documents the FDA-driven pediatric expansions for multiple DAAs and corresponding policy updates. Epclusa and Harvoni indications were expanded to include pediatric individuals aged 3 years and older (earlier 2020–2021 notes reflect stepwise expansions from age 6/17 kg to age 3 and availability of oral pellet formulations). Mavyret’s pediatric indication was expanded to include all pediatric individuals aged 3 years and older with removal of earlier weight restrictions and availability of an oral pellet form. These pediatric expansions are recorded in the history and update notes through 2021 and reiterated in subsequent reviews (policy updates in 2021 and referenced again in 2025 updates).

Coding

HCPCS codes listedHCPCS

S0145

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

Referenced HCPCS / J-codes historically removed/addedHCPCS

S0145	Added for Pegasys due to criteria change; managed by both pharmacy and medical (effective 09/05/25 notification)
S0148	Historically referenced; removed in earlier updates
J9213	Historically removed
J9214	Historically removed
J8499	Removed

Pharmacy-managed products (listed drugs — no code-level billing in this part)mixed

NDC	Various NDCs for products referenced under pharmacy benefit (not enumerated in this part)

Provider Actions / Prior Authorization & Documentation

Documentation Required

Medical record documentation

Office visit notes must document diagnosis of chronic hepatitis C, relevant history and physical evaluation, HCV genotyping results, the specific length of therapy requested, and a medication history to support medical necessity.

Prior Authorization

Prior authorization for pegylated interferons

Pegylated interferons (including Pegasys) require prior authorization for treatment of chronic hepatitis C and use must follow current guideline recommendations. HCPCS code S0145 is listed for Pegasys and is referenced in prior authorization/coding sections.

Background & Evidence

Background and clinical context: Hepatitis C infection can present as acute or chronic disease; about ~4 million Americans have been infected and approximately 74% have chronic infection. Disease progression can be silent for decades, with 20–30% developing cirrhosis within 10–20 years and 5–10% progressing to end-stage liver disease; cirrhosis increases hepatocellular carcinoma risk and is the most common indication for liver transplantation in the U.S.

There are 6 HCV genotypes with substantial genetic heterogeneity that influences therapeutic choices. Achieving a sustained virologic response (SVR) is the accepted surrogate endpoint for cure (SVR defined in the policy as HCV RNA undetectable at 12 or 24 weeks after therapy in cited trials and historically as clearance at 24 weeks) and is associated with clinical benefit (reduced fibrosis, lower relapse risk, and survival benefit).

DAA evolution and efficacy: Newer all-oral DAAs (for example Epclusa, Mavyret, Vosevi, Harvoni, Zepatier, Sovaldi) produce high SVR rates (many trials reporting SVR12 >90–95% and multiple phase 3 trials demonstrating pangenotypic and high cure rates). Epclusa ASTRAL trials reported ~99% SVR12 across genotypes; Vosevi POLARIS trials showed SVR12 in the mid-90s including in DAA-experienced populations; Mavyret phase 3 programs reported SVR12 typically in the high-90s across many populations.

Special populations considerations: The policy directs clinicians to follow AASLD/IDSA guidance for persons with HIV coinfection, post-transplant recurrence, decompensated cirrhosis (Child-Pugh B or C), chronic kidney disease and pediatric patients. Transplant-related recurrence and retreatment are recognized as complex and are to be managed per current guidelines. The policy notes reduced SVR probabilities in some subgroups and emphasizes guideline-directed selection, RAS testing when recommended, and individualized review for advanced liver disease or other complicating conditions.

Label	Value
ASTRAL trials (Epclusa)	Four phase‑3 ASTRAL trials; 12‑week SOF/VEL produced SVR12 ≈99% across genotypes in ASTRAL‑1; high rates in ASTRAL‑2/3 and data in decompensated cirrhosis (ASTRAL‑4) with SOF/VEL±RBV showing SVR12 up to 94% in some arms; primary endpoint defined as HCV RNA <15 IU/mL at 12 weeks (SVR12).
POLARIS trials (Vosevi)	POLARIS‑1 and ‑4: SOF/VEL/VOX achieved SVR12 of 96% and 98% vs performance goal; SVR12 fell to 93% in cirrhotics who failed NSSA treatment; POLARIS‑2 8‑week regimen did not meet prespecified performance (overall SVR12 95%), leading to no 8‑week approval.
Mavyret phase‑3 trials	Eight phase‑3 trials: overall high efficacy with SVR12 97%‑100% in most populations; some subgroups had lower SVR12 (89%‑95%); approved 8‑week course for many treatment‑naive GT1‑6 noncirrhotic patients and 12‑ or 16‑week options per prior treatment/cirrhosis status.
Harvoni ION trials	ION trials: SVR rates 94% for 8‑week, 99% for 12‑week, and 98% for 24‑week regimens in treatment‑naive noncirrhotic individuals; 8‑week relapse risk higher when baseline HCV RNA ≥6 million IU/mL (FDA recommends considering 8‑week only if viral load <6 million IU/mL).
Guideline reference	Policy follows AASLD/IDSA guideline recommendations (multiple updates cited; guideline resource referenced for up‑to‑date regimen selection).
Prescribing information references	Prescribing information cited for Harvoni, Epclusa, Vosevi, Mavyret, Zepatier, Sovaldi, Pegasys with revision dates through 2024–2025 (policy reviewed prescribing information and incorporated FDA‑labeled indications/lengths).

Revision History

2024-12addition

Added FDA-approved uses for brand sofosbuvir-velpatasvir, brand ledipasvir-sofosbuvir, Sovaldi (sofosbuvir) and Zepatier (elbasvir-grazoprevir). (Dec 2024)

2025-01-01addition

Policy header/section updates reflecting new FDA uses and new policy section headers added for Metallic formulary plans (Jan 2025).

2025-05clarification

Clarified that non-formulary exception review authorizations for all drugs listed in this policy may be approved up to 12 months; re-authorization considered investigational (May 2025).

Policy Summary

PayerPremera Bluecross

PolicyHepatitis C Antiviral Therapy

Policy CodePolicy 5.01.606

Change TypeFDA indications, section reorganization, coverage clarifications

Effective DateMay 1, 2025

Next Review DateN/A

Key ActionSubmit office visit notes documenting diagnosis, genotyping, requested therapy length, medication history and supporting documentation to demonstrate medical necessity.

SourceLink

On This Page

Drug-specific FDA Indications and Lengths of Therapy

Drug-specific FDA indications and typical lengths of therapy. Deviations from AASLD/IDSA-recommended durations are considered investigational unless supported by guideline-directed exceptions or strong clinical rationale.

ALL of the following

Epclusa (sofosbuvir-velpatasvir)
- FDA-approved for a 12-week course in adults and pediatric patients aged ≥3 years for genotypes 1–6 without cirrhosis or with compensated cirrhosis (Child-Pugh A).
- For decompensated cirrhosis (Child-Pugh B or C), Epclusa is FDA-approved in combination with ribavirin for select patients per labeling and guidelines.
Harvoni (ledipasvir-sofosbuvir)
- FDA-approved for a 12-week course in adults and pediatric patients aged ≥3 years for specified genotype 1 and other indications per labeling; some treatment-experienced genotype 1 with compensated cirrhosis may require 24 weeks per FDA labeling and guideline recommendations.
- Use in decompensated cirrhosis and post-transplant settings per FDA labeling in combination with ribavirin as indicated.
Mavyret (glecaprevir-pibrentasvir)
- FDA-approved for an 8-week course in treatment-naive adults and pediatric patients aged ≥3 years with genotypes 1–6 without cirrhosis or with compensated cirrhosis (Child-Pugh A).
- Longer courses (e.g., 12 weeks) are FDA-approved for certain treatment-experienced individuals per labeling.
Sovaldi (sofosbuvir)
- FDA-approved in combination regimens per labeling; length of therapy varies by regimen, genotype, prior treatment status, and presence of cirrhosis—follow FDA labeling and AASLD/IDSA guidance.
Vosevi (sofosbuvir-velpatasvir-voxilaprevir)
- FDA-approved for specific treatment-experienced populations; duration per labeling (typically 12 weeks) and per guideline recommendations.
Zepatier (elbasvir-grazoprevir)
- FDA-approved for specified genotypes and clinical situations; duration and use informed by baseline RAS testing for certain genotypes per labeling and guidelines.
Pegylated interferons (Pegasys, PegIntron)
- Require prior authorization; use only in accordance with current guidelines when applicable.
Deviations
- Deviations from guideline-recommended durations or FDA-approved indications (including non‑labeled durations or off‑label uses) are considered investigational unless clearly supported by current AASLD/IDSA guidance and documented clinical rationale.

Genotyping and Resistance Testing

Genotyping and resistance testing are required when recommended by guidelines to inform regimen selection.

ALL of the following

HCV genotype testing is medically necessary when guideline-recommended to guide antiviral selection and duration.
Resistance-associated substitution (RAS) testing (including NS5A RAS testing) is medically necessary when recommended by AASLD/IDSA or FDA labeling to inform choice of regimen (e.g., elbasvir-containing regimens, certain retreatment scenarios).
Testing results must be documented in the medical record with interpretation and treatment decision rationale.

Approval Lengths and Reauthorization

Authorization lengths and reauthorization rules.

ALL of the following

Initial authorization may be provided for up to 12 months to allow completion of FDA‑approved treatment courses and any guideline‑recommended adjunct therapy (e.g., ribavirin).
Re-authorization for continuation of the same antiviral regimen beyond the initial approved course is generally not applicable; requests for additional or repeat courses (including retreatment) will be reviewed based on current AASLD/IDSA guidance and individualized clinical circumstances.
Requests for durations or retreatment approaches that deviate from guideline recommendations are considered investigational and require strong clinical justification and specialty review.

General Coverage / Medical Necessity (overview from this part)

Overview of general coverage, plan-specific formulary sections, and requirement to follow guideline and FDA prescribing information.

ALL of the following

Coverage varies by member's formulary; sections 1–3 above summarize plan-specific preferred agents and exceptions — always verify the member's plan and formulary placement prior to prescribing.
All treatment must follow current AASLD/IDSA guidance and the US FDA-approved prescribing information for the selected regimen; when guideline recommendations differ from FDA labeling, both sources should be considered and documented.
Prior authorization is required per plan rules and documentation must include diagnosis, genotype/RAS testing when performed, prior treatment history, cirrhosis status, and prescriber specialty or consultation notes.

Pediatric Indication Updates

Pediatric Indication Updates — consolidated and preserved.

ALL of the following

Epclusa (sofosbuvir-velpatasvir): FDA-approved for a 12-week course in adults and pediatric patients aged ≥3 years for genotypes 1–6 without cirrhosis or with compensated cirrhosis; in select pediatric patients with decompensated cirrhosis, Epclusa may be used in combination with ribavirin per FDA labeling and guidelines.
Harvoni (ledipasvir-sofosbuvir): FDA-approved for a 12-week course in adults and pediatric patients aged ≥3 years for specified genotype 1 indications; certain treatment-experienced patients with compensated cirrhosis may require 24 weeks as per labeling and guidelines.
Mavyret (glecaprevir-pibrentasvir): FDA-approved for an 8-week course in treatment-naive adults and pediatric patients aged ≥3 years with genotypes 1–6 without cirrhosis or with compensated cirrhosis; 12-week courses are approved for selected treatment-experienced populations per labeling.
Sovaldi, Vosevi, Zepatier: Pediatric indications and ages vary by agent and regimen; follow current FDA labeling for age approvals and regimen-specific recommendations.
For all pediatric patients, regimen choice, dosing, and duration must follow FDA-approved pediatric indications and the most recent AASLD/IDSA pediatric guidance when available; any use outside labeled pediatric indications is considered investigational and requires specialty justification and prior authorization.

SVRSustained virologic response: clearance of HCV RNA by qualitative analysis 24 weeks after therapy cessation (SVR definition used as surrogate endpoint)

RASResistance-associated substitution: genetic mutations that may impact DAA effectiveness; testing is medically necessary when guideline-recommended to guide regimen selection

Compensated cirrhosis (Child-Pugh A)Liver disease stage used to determine DAA selection/duration; defines compensated cirrhosis as Child-Pugh A

Decompensated cirrhosis (Child-Pugh B or C)More advanced liver disease (Child-Pugh B or C); treated per current guideline recommendations, often with specialist care

Section 1 DefinitionIncentive, Open, and Select formulary plans and plans with no pharmacy benefit coverage (Rx plans A1, A2, B3, B4, C4, F1, G3)

Section 2 DefinitionEssentials formulary plans (Rx plans E1, E3, E4)

Section 3 DefinitionIndividual/Small Group/Student ISHIP Metallic formulary plans (Rx plans M1, M2, M4)