mhn Harvoni (Ledipasvir/Sofosbuvir) Coverage Update

Coverage and Medical Necessity Criteria

inv-01: Initial Approval — Hepatitis C Infection — Covered when ALL of the following are met:

Covered when ALL of the following are met:

Initial Approval Criteria: 1. Diagnosis of HCV infection as evidenced by detectable serum HCV RNA by quantitative assay within the last 6 months; 2. Prescribed by or in consultation with a gastroenterologist, hepatologist, infectious disease specialist, or provider with certified HCV training (see Appendix F); 3. Age ≥ 3 years; 4. Confirmed HCV genotype 1, 4, 5, or 6 (documentation and lab copies required); 5. Documentation of treatment status (treatment‑naïve or treatment‑experienced); 6. Documentation of cirrhosis status (no cirrhosis, compensated, or decompensated); 7. One of the following regarding preferred product use: a) member must use brand Epclusa unless contraindicated or clinically significant adverse effects; b) if contraindicated/adverse effects to brand Epclusa, member must use authorized generic Harvoni; c) if contraindicated/adverse effects to both brand Epclusa and authorized generic Harvoni, clinical documentation is required; 8. Life expectancy ≥ 12 months with HCV treatment; 9. Prescribed regimen is consistent with an FDA or AASLD‑IDSA recommended regimen (see Section V); 10. Dose does not exceed ledipasvir 90 mg/sofosbuvir 400 mg per day and 1 tablet per day.

For treatment‑naïve adults without cirrhosis and baseline HCV RNA < 6 million IU/mL, an 8‑week Harvoni regimen may be approved per Section V; approved duration up to 24 weeks consistent with dosing guidance.

inv-02: Continued Therapy — Hepatitis C Infection — Continued coverage when ALL of the following are met:

Continued coverage when ALL of the following are met:

Continued Therapy Criteria: 1. Member meets one of the following: a) currently receiving medication via the benefit or previously met initial approval criteria; b) member is currently receiving medication and is in a state/product with continuity of care regulations; c) documentation supports member has completed ≥28 days of Harvoni treatment; 2. Member is responding positively to therapy; 3. Prescribed regimen is consistent with an FDA or AASLD‑IDSA recommended regimen (see Section V); 4. Dose does not exceed ledipasvir 90 mg/sofosbuvir 400 mg per day and 1 tablet per day.

Approval duration: up to a total of 24 weeks consistent with dosing guidance.

inv-03: Other diagnoses/indications — Coverage for other indications requires one of the following and adherence to formulary/off‑label policies:

Coverage for other indications requires one of the following and adherence to formulary/off‑label policies:

Other Indications Logic: 1. Member must use brand Epclusa for the requested indication unless contraindicated or clinically significant adverse effects are present; 2. If contraindicated/adverse effects to brand Epclusa, member must use authorized generic Harvoni; 3. If contraindicated/adverse effects to both, clinical documentation is required; 4. If the drug underwent a label change within the last 6 months not reflected in this policy, follow the referenced formulary/no‑coverage or non‑formulary policies (e.g., CP.CPA.190); 5. If the requested use is not listed in Section III and criterion for recent label change does not apply, refer to the off‑label use policy (CP.CPA.09).

Operational cross‑references to CP.CPA.190 and CP.CPA.09; coadministration with omeprazole ≤20 mg is not an acceptable justification to avoid Epclusa (see Appendix E).

inv-04: Dosage and Administration by genotype and clinical status — Dosing regimens as referenced to FDA labeling and AASLD-IDSA (Dec 2023)

Dosing regimens as referenced to FDA labeling and AASLD‑IDSA (Dec 2023) — apply by genotype, prior treatment status, cirrhosis status, and clinical context.

Genotype 1 — Treatment‑naïve without cirrhosis and HIV‑uninfected with HCV RNA < 6 million IU/mL: One tablet PO once daily for 8 weeks.HCV viral load < 6 million IU/mL; pediatric weight‑based formulations apply per labeling

Reference: FDA labeling and AASLD‑IDSA (Dec 2023)

Genotype 1 — Treatment‑naïve without cirrhosis (not meeting 8‑week criteria) or with compensated cirrhosis: One tablet PO once daily for 12 weeks.

Reference: FDA labeling and AASLD‑IDSA

Genotype 1 — Treatment‑experienced without cirrhosis: One tablet PO once daily for 12 weeks.

Reference: FDA labeling

inv-05: Management of incomplete adherence and treatment interruptions — Recommended actions for DAA treatment interruptions

Recommended actions for DAA treatment interruptions based on timing (<28 days vs ≥28 days) and length of interruption.

Interruptions during the first 28 days of therapy: If missed ≤7 days: restart DAA immediately and complete the originally planned duration (8 or 12 weeks). If missed ≥8 days: restart immediately and obtain HCV RNA as soon as possible; if HCV RNA is negative, complete originally planned course (consider extending by 4 weeks for genotype 3 and/or cirrhosis); if HCV RNA is positive or not obtained, extend treatment by 4 weeks.

Applies to treatment‑naïve patients without or with compensated cirrhosis receiving Mavyret or Epclusa per Appendix G; manage other regimens/populations with expert consultation.

Interruptions after ≥28 days of therapy: If missed ≤7 days: restart and complete original duration. If missed 8–20 consecutive days: restart, obtain HCV RNA; if RNA negative, complete original course (consider +4 weeks for genotype 3 and/or cirrhosis); if RNA positive or not obtained, stop and retreat per AASLD‑IDSA retreatment recommendations. If missed ≥21 consecutive days: stop DAA treatment and assess for SVR12; if SVR12 not achieved, retreat per AASLD‑IDSA recommendations.

Applies to specified populations and regimens in Appendix G; consult expert for prior‑DAA treatment, other regimens, posttransplant, or decompensated cirrhosis.

Non‑FDA approved indications that are not specifically addressed by this policy are not authorized for coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the plan’s off‑label use policy (CP.CPA.09) and any applicable evidence of coverage documents. Requests for off‑label uses should include supporting literature and clinical rationale per the off‑label policy to be considered.

The policy identifies specific examples of unacceptable medical justification for inability to use preferred or alternative agents; these were added to Appendix E and incorporated into the criteria during prior reviews. For instance, prior revisions clarified that co‑administration with amiodarone (as a reason to avoid certain regimens) is listed as an unacceptable rationale for bypassing preferred agents and may not be accepted without additional clinical justification.

Requests for indications that are not FDA‑approved and that lack sufficient evidence per the off‑label use policy may be considered not medically necessary. Providers should follow CP.CPA.09 and submit supporting clinical evidence if seeking coverage for off‑label indications.

Policy edits across recent reviews included reorganizing steerage toward preferred agents, clarifying unacceptable rationales for bypassing preferred products, and updating dosing tables. The document notes removal or modification of some prior redirections and added Appendix E to list unacceptable justifications; however, explicit 'not medically necessary' statements beyond those tied to off‑label and unsupported indications are not presented in this section of the policy.

Key Coding and Eligibility Thresholds

Baseline HCV RNA for 8‑week regimen eligibility

8-week regimen baseline HCV RNA threshold< 6 million IU/mL

Evidence sourceION-3 trial support for 8-week Harvoni in treatment-naïve noncirrhotic patients with baseline HCV RNA <6 million IU/mL

Applies toTreatment‑naïve adults without cirrhosis, genotype 1

Provider Requirements, Prior Authorization, and Denial Risks

Prior Authorization

Prior Authorization Required

Prior authorization is required for initial therapy. Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria, including evidence of detectable serum HCV RNA by quantitative assay within the last 6 months, documented genotype, treatment status, and cirrhosis status. Requests for non‑FDA approved indications not addressed in this policy require sufficient documentation per the off‑label use policy (CP.CPA.09) and may be denied if documentation is incomplete.

Required documentation: office chart notes, lab results, or other clinical information
Detectable serum HCV RNA within last 6 months
Documented HCV genotype, treatment status (naïve or experienced), and cirrhosis status

Step Therapy

Preferred Product Requirement

The policy requires use of Epclusa (sofosbuvir/velpatasvir) as the preferred product when clinically appropriate. Brand Epclusa is the preferred alternative; members must use brand Epclusa unless contraindicated or clinically significant adverse effects are experienced. If the member has contraindications or clinically significant adverse effects to brand Epclusa, the authorized generic version of Harvoni (ledipasvir/sofosbuvir) must be used. Clinical documentation is required when both Epclusa and the authorized generic Harvoni cannot be used.

Background and Clinical Context

Ledipasvir/sofosbuvir (Harvoni) is a fixed‑dose combination direct‑acting antiviral composed of ledipasvir (an NS5A inhibitor) and sofosbuvir (a nucleotide analog NS5B polymerase inhibitor). It is FDA‑approved for treatment of hepatitis C virus infection in adults and pediatric patients age ≥3 years for specified genotypes and clinical scenarios. Dosing recommendations vary by genotype, prior treatment status, and cirrhosis/transplant status and are provided in the policy’s dosing tables and referenced to FDA labeling and AASLD‑IDSA guidance.

Definitions and Clinical Scoring

Harvoni

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

Brand nameHarvoni

FDA‑approved agesAdults and pediatric patients age ≥3 years (see dosing tables).

Child-Pugh Score

PurposeScoring system to classify severity of liver disease based on clinical and laboratory parameters.

Parameters usedBilirubin, albumin, INR, presence/severity of ascites, and encephalopathy.

Classification

Policy Revision History and Material Changes

05.30.24policy_revision

3Q 2024 annual review: policy/criteria updated to include generic ledipasvir/sofosbuvir, removed 'chronic' qualifier from HCV criteria per AASLD‑IDSA, removed 'preferred' designation from brand Epclusa redirection, and added Appendix G for guidance on incomplete adherence and AASLD‑IDSA management of treatment interruptions.

07.15.25policy_revisionLatest

3Q 2025 annual review: continued therapy criteria revised to add requirement that the prescribed regimen is consistent with an FDA or AASLD‑IDSA recommended regimen; minimum treatment duration for continued therapy changed from 60 days to 28 days and requirement for specific confirmed genotype was removed.

OpenPayer

Clinical Policy: Ledipasvir/Sofosbuvir (Harvoni)