ModifiedmhnPolicy CP.CPA.175

Ledipasvir/sofosbuvir (Harvoni) therapy for chronic hepatitis C

Medical necessity and prior authorization criteria for use of ledipasvir/sofosbuvir (Harvoni) for treatment of chronic hepatitis C virus (HCV) infection in commercial line of business for patients age ≥3 years with genotypes 1, 4, 5, or 6.

Policy Summary

Payermhn

PolicyLedipasvir/sofosbuvir (Harvoni) therapy for chronic hepatitis C

Policy CodePolicy CP.CPA.175

Change TypeMaterial revision — added Appendix Gupdated product inclusion and continued therapy criteria

Effective DateNov 1, 2016

Next Review Date

Key ActionSubmit prior authorization with documentation of detectable HCV RNA within 6 months, genotype confirmation, cirrhosis and treatment status, and regimen consistent with FDA or AASLD‑IDSA recommendations.

SourceLink

POLICY UPDATE CHANGES

Appendix G was added for guidance on incomplete adherence and AASLD-IDSA recommended management of treatment interruptions.

Policy/criteria section was revised to also include generic ledipasvir/sofosbuvir and to remove the qualifier of 'chronic' from HCV criteria.

For continued therapy criteria, 'Prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen' was added and minimum treatment duration options were revised.

≥3minimum patient age

1,4,5,6genotypes covered

≤24wmax approval duration

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8–12wcommon adult duration

AASLD-IDSAguideline ref

Coverage Criteria for Ledipasvir/Sofosbuvir (Harvoni)

Initial Approval Criteria

Covered when ALL of the following are met:

ALL of the following

Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
Diagnosis of HCV infection as evidenced by detectable serum HCV RNA levels by quantitative assay in the last 6 months.
Prescribed by or in consultation with a gastroenterologist, hepatologist, infectious disease specialist, or provider who has expertise in treating HCV based on a certified training program (see Appendix F).
Age ≥ 3 years.
Confirmed HCV genotype is 1, 4, 5, or 6; chart note documentation and copies of lab results are required.
Documentation of treatment status of the member (treatment-naïve or treatment-experienced).
Documentation of cirrhosis status of the member (no cirrhosis, compensated cirrhosis, or decompensated cirrhosis).
One of the following must apply:
- Member must use brand Epclusa, unless contraindicated or clinically significant adverse effects are experienced (see Appendix E).
- If member has clinically significant adverse effects or contraindications to brand Epclusa, member must use authorized generic version of Harvoni.
- Member has clinically significant adverse effects or contraindications to brand Epclusa and authorized generic version of Harvoni (clinical documentation required).
Clinical note
Coadministration with omeprazole up to 20 mg is not considered acceptable medical justification for inability to use Epclusa.
Life expectancy ≥ 12 months with HCV treatment.
Prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen (see Section V Dosage and Administration).
ALL of the following
- Dose does not exceed ledipasvir 90 mg/sofosbuvir 400 mg per day.
- Dose does not exceed 1 tablet per day.

Continuation Therapy Criteria

Continued therapy is covered when ONE of the continuation conditions is met AND ALL other listed conditions apply:

ALL of the following

Member must meet one of the following:
- Currently receiving medication via Centene benefit or member has previously met initial approval criteria.
- Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B).
- Documentation supports that member is currently receiving Harvoni for HCV infection and has recently completed at least 28 days of treatment with Harvoni.
Member is responding positively to therapy.

Dosage and Administration — Genotype‑Specific Dosing

Initial and genotype-specific dosing regimens (regimens must match FDA labeling or AASLD‑IDSA recommendations and dosing must be appropriate for genotype, cirrhosis status, and prior treatment):

ALL of the following

Genotype 1: Treatment-naïve without cirrhosis, HIV‑uninfected, and HCV viral load < 6 million IU/mL: One tablet PO QD for 8 weeks (off‑label AASLD‑IDSA supported indication).
Genotype 1: Treatment‑naïve without cirrhosis (not meeting 8‑week criteria) or with compensated cirrhosis: One tablet PO QD for 12 weeks.
Genotype 1: Treatment‑experienced without cirrhosis: One tablet PO QD for 12 weeks.
Pediatric and weight-based dosing:

Adherence and Treatment Interruptions

Adherence and treatment interruption management (AASLD‑IDSA recommendations):

ALL of the following

A treatment interruption of < 7 days is unlikely to impact SVR12; minimal data exist on adherence thresholds for DAAs.
Interruptions during the first 28 days of DAA therapy
- If missed ≤ 7 days, restart DAA therapy immediately and complete therapy for originally planned duration (8 or 12 weeks).
- If missed ≥ 8 days, restart DAA therapy immediately and obtain HCV RNA test as soon as possible. If HCV RNA is negative, complete originally planned DAA treatment course; consider extending treatment by 4 weeks for patients with genotype 3 and/or cirrhosis. If HCV RNA is positive or not obtained, extend DAA treatment for an additional 4 weeks.
Interruptions after receiving ≥ 28 days of DAA therapy

Coding and Clinical Thresholds

NDC / Product codes (referenced)NDC

NDC	Product NDCs not listed explicitly in this part of the document; product strengths and forms are described.

HCV RNA (baseline viral load) — < 6,000,000 IU/mL for consideration of 8-week regimen

HCV RNA (baseline)Baseline quantitative serum HCV RNA < 6,000,000 IU/mL is required for consideration of an 8-week Harvoni regimen in treatment‑naïve, noncirrhotic adults (per ION‑3 and policy criteria)

Evidence timingDetectable serum HCV RNA must be documented by quantitative assay within the last 6 months for prior authorization

Applicability8-week option applies to treatment‑naïve adult members without cirrhosis and genotype 1 when baseline HCV RNA is < 6 million IU/mL

Child-Pugh class — A = 5-6; B = 7-9; C = 10-15

Child‑Pugh class ATotal score 5–6 points

Child‑Pugh class B

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must meet initial or continuation criteria and include documentation supporting the diagnosis and medical necessity. A detectable serum HCV RNA by quantitative assay within the last 6 months is required for initial approval. Prescriptions must be by or in consultation with a gastroenterologist, hepatologist, infectious disease specialist, or other provider with demonstrated HCV expertise when required by the criteria.

Detectable serum HCV RNA within 6 months for initial approval
Prescribed by or in consultation with an HCV specialist when required (see Appendix F)
Provider must submit office notes, lab results, or other clinical information supporting that member meets all approval criteria

Prior Authorization

Regimen Consistency and Product Inclusion

Prior authorization will only be approved if the prescribed regimen and dosing are consistent with FDA labeling or AASLD‑IDSA recommended regimens. Regimen requests must reference applicable Dosage and Administration guidance in Section V. Generic ledipasvir/sofosbuvir is included in the policy and may be considered when the regimen and dose limits align with policy limits.

Background

Ledipasvir/sofosbuvir (Harvoni) is a fixed‑dose combination of an NS5A inhibitor (ledipasvir) and an NS5B nucleotide polymerase inhibitor (sofosbuvir) approved for treatment of hepatitis C virus infection in adults and pediatric patients aged ≥3 years for specified genotypes and cirrhosis statuses. The product is available in tablet and pediatric formulations and dosing and duration should follow FDA labeling or AASLD‑IDSA recommendations. Clinicians should note the boxed warning for hepatitis B virus reactivation with direct‑acting antivirals and monitor patients during and after HCV treatment.

Definitions

Harvoni — Fixed-dose combination product description

Product compositionFixed‑dose combination of ledipasvir (NS5A inhibitor) and sofosbuvir (NS5B nucleotide analog polymerase inhibitor)

Indication summaryApproved for treatment of chronic HCV infection in adults and pediatric patients ≥3 years for specified genotypes and cirrhosis status

Dosage strengths/formsAvailable as tablets (90/400 mg and 45/200 mg) and pediatric pellets (33.75/150 mg) per dosing section

Child-Pugh score — Scoring system for liver disease severity (A/B/C definitions)

PurposeScoring system to assess severity of chronic liver disease and guide management decisions

ComponentsBased on bilirubin, albumin, INR, presence/degree of ascites, and encephalopathy

Policy Summary

Payermhn

PolicyLedipasvir/sofosbuvir (Harvoni) therapy for chronic hepatitis C

Policy CodePolicy CP.CPA.175

Change TypeMaterial revision — added Appendix Gupdated product inclusion and continued therapy criteria

Effective DateNov 1, 2016

Next Review Date

SourceLink

On This Page

Prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen (see Section V Dosage and Administration).

ALL of the following

Dose does not exceed ledipasvir 90 mg/sofosbuvir 400 mg per day.
Dose does not exceed 1 tablet per day.

Weight ≥ 35 kg: One tablet (sofosbuvir 400 mg / ledipasvir 90 mg) per day. Weight ≥ 17 to < 35 kg: One tablet (sofosbuvir 200 mg / ledipasvir 45 mg) per day. Weight < 17 kg: One packet of pellets (sofosbuvir 150 mg / ledipasvir 33.75 mg) per day.

Genotype 1, 4, 5, or 6 with decompensated cirrhosis: One tablet PO QD plus low initial dose of ribavirin (600 mg, increased as tolerated) for 12 weeks (or Harvoni for 24 weeks if ribavirin‑intolerant); alternative regimens per AASLD‑IDSA guidance for prior sofosbuvir‑ or NS5A‑exposed patients may require extended duration and/or ribavirin.

Genotype 4, 5, or 6 (without cirrhosis or with compensated cirrhosis): One tablet PO QD for 12 weeks.

References: FDA‑approved labeling and AASLD‑IDSA guidelines (updated December 2023). AASLD/IDSA guidelines are periodically updated; refer to the most current guidance for final regimen selection.

If missed ≤ 7 days, restart DAA therapy immediately and complete therapy for originally planned duration (8 or 12 weeks).

If missed 8–20 consecutive days, restart DAA therapy immediately and obtain HCV RNA test as soon as possible. If HCV RNA is negative, complete originally planned DAA treatment course; consider extending treatment by 4 weeks for patients with genotype 3 and/or cirrhosis. If HCV RNA is positive or not obtained, stop treatment and retreat according to AASLD‑IDSA retreatment recommendations.

If missed ≥ 21 consecutive days, stop DAA treatment and assess for SVR12. If SVR12 not achieved, retreat according to AASLD‑IDSA retreatment recommendations.

These recommendations generally apply to treatment‑naïve patients without cirrhosis or with compensated cirrhosis receiving regimens such as Mavyret or Epclusa; patients with prior DAA exposure, post‑transplant status, or decompensated cirrhosis should be managed in consultation with an HCV expert.

Total score 7–9 points

Child‑Pugh class CTotal score 10–15 points

HCV viral load threshold for 8-week regimen — < 6 million IU/mL

8‑week regimen thresholdHCV viral load < 6 million IU/mL is the threshold for considering an 8‑week Harvoni course in treatment‑naïve, noncirrhotic genotype 1 adults

Source trial/policy noteION‑3 data and policy language reference the <6 million IU/mL threshold supporting comparable SVR‑12 rates for 8 vs 12 weeks

Patient populationSpecifically applies to treatment‑naïve adult members without cirrhosis and genotype 1

Weight thresholds for pediatric dosing

>= 35 kgUse adult tablet: sofosbuvir 400 mg / ledipasvir 90 mg once daily

17 to <35 kgUse 45/200 mg tablet (sofosbuvir 200 mg / ledipasvir 45 mg) once daily

< 17 kgUse pellets: sofosbuvir 150 mg / ledipasvir 33.75 mg (one packet) once daily

Requested regimen must be consistent with FDA labeling or AASLD‑IDSA guidance (see Section V)
Dose limits: ledipasvir 90 mg/sofosbuvir 400 mg once daily; 1 tablet per day (see policy for pediatric weight-based dosing)
Generic ledipasvir/sofosbuvir is included and evaluated under the same regimen/dosing consistency requirements

Step Therapy

Product Preference / Step Edit (Epclusa First-Line)

The policy contains a product preference/step edit directing use of Epclusa as the first‑line agent when applicable. Members must use Epclusa unless there is an acceptable contraindication or clinically significant adverse effect documented. If Epclusa cannot be used, the authorized generic of Harvoni or other alternatives may be considered per the criteria.

Members must use Epclusa as preferred product when applicable unless contraindicated or unacceptable (see Appendix E for acceptable reasons)
If contraindicated or adverse effects to Epclusa, authorized generic Harvoni may be required prior to other agents
Coadministration with omeprazole up to 20 mg is NOT an acceptable reason to bypass Epclusa

Note

Preferred Agent Redirection

The policy includes preferred‑agent redirections and step edit logic. Some previous redirections were removed where AASLD/PI overlap was not supported. Requests that attempt to bypass preferred agents without an authorized clinical rationale or required documentation may be denied.

Preferred redirections to alternate agents are provided in the policy where clinically supported; some redirections (e.g., to Vosevi) were removed when not guideline‑supported
Use of an unauthorized rationale to bypass a preferred agent may result in denial
Clinical documentation is required to justify use of non‑preferred agents (e.g., contraindication, documented adverse reaction)

Denial Risk

Reasons for Potential Denial

Requests may be denied for failure to submit required supporting documentation or for requests for non‑FDA indications when sufficient evidence is not provided. Lack of documentation supporting inability to use the preferred product (Epclusa) or lack of specialist consultation/training where required are common reasons for denial.

Denial risk if office notes, labs, or other clinical information supporting criteria are not provided
Denial risk for requests for non‑FDA indications without evidence per off‑label policy (CP.CPA.09) or applicable coverage policy
Denial risk if an unacceptable rationale is used to bypass Epclusa (see Appendix E)

Class definitionsTotal points map to classes A (5–6), B (7–9), C (10–15)

Child-Pugh Score — Class points mapping (A/B/C)

Points to class mappingTotal Child‑Pugh points: 5–6 = Class A; 7–9 = Class B; 10–15 = Class C

Example component scoringBilirubin, albumin, INR, ascites, and encephalopathy are each scored 1–3 points to calculate total

Clinical useUsed to determine compensated vs decompensated cirrhosis and influence regimen/duration decisions

Treatment-experienced — Definition for treatment-experienced patients

DefinitionTreatment‑experienced: patients with prior HCV therapy documented (e.g., prior peginterferon ± ribavirin with or without an HCV protease inhibitor) and recorded treatment status in the chart

Implication for dosingTreatment‑experienced adults without cirrhosis are generally treated with 12 weeks of Harvoni per dosing guidance

Documentation requirementPrior authorization requires documentation of treatment‑experienced or treatment‑naïve status in the medical record