WHA

ZEPATIER (elbasvir-grazoprevir)

SELF-ADMINISTRATION - oral

Diagnosis considered for coverage:

  • Chronic Hepatitis C Virus (HCV) – Zepatier is a fixed-dose combination product containing elbasvir, a hepatitis C virus (HCV) NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor, and is indicated for treatment of chronic HCV genotype 1 or 4 infection in adult and pediatric patients 12 years of age and older or weighing at least 30 kg. ZEPATIER is indicated for use with ribavirin in certain patient populations.

Coverage Criteria:

1. Request for treatment of chronic HCV, genotype 1a, treatment-naïve or treatment-experienced to peginterferon/ribavirin with or without an NS3/4A protease inhibitor, WITHOUT baseline NS5A polymorphisms (12 weeks):

  • Dose does not exceed one tablet (50 mg or elbasvir and 100 mg of grazoprevir) taken orally once daily for 12 weeks; AND
  • Prescribed by or in consultation with a hepatologist, gastroenterologist, or infectious disease (ID) specialist; AND
  • Medical records (e.g., chart notes, laboratory values) document ONE of the following:
    • Patient is treatment-naive
    • Patient has prior treatment failure with peginterferon alfa plus ribavirin
    • Patient has prior treatment failure with peginterferon alfa plus ribavirin with an NS3/4A protease inhibitor (e.g., boceprevir, simeprevir, or telaprevir); AND
  • Medical records (e.g., chart notes, laboratory values) document all of the following:
    • HCV genotype 1a
    • Detectable serum HCV RNA level by quantitative assay in the last 6 months
    • Patient does not have moderate to severe hepatic impairment (i.e., does not have Child-Pugh class B or class C)
    • Patient has tested negative for a baseline NS5A resistance-associated polymorphism (i.e., polymorphisms at amino acid positions 28, 30, 31 or 93); AND
  • Patient is not receiving Zepatier in combination with another HCV direct-acting antiviral agent (e.g., inhibitors of the NS3/4A protease, the NS5A protein, or the NS5B polymerase); AND
  • Patient has a contraindication (e.g., safety concerns, not indicated for patient's age/weight) or intolerance to BOTH of the following:
    • Brand Epclusa (sofosbuvir/velpatasvir) OR brand Harvoni (ledipasvir/sofosbuvir)
    • Mavyret (glecaprevir/pibrentasvir)
  • For patients with prior treatment failure with peginterferon alfa plus ribavirin plus an HCV NS3/4A protease inhibitor (e.g., boceprevir, simeprevir, or telaprevir) only: Will be used in combination with ribavirin.

2. Request for treatment of chronic HCV, genotype 1a, treatment-naïve or treatment-experienced to peginterferon/ribavirin with or without an NS3/4A protease inhibitor; WITH baseline NS5A polymorphisms (16 weeks):

  • Dose does not exceed one tablet (50 mg or elbasvir and 100 mg of grazoprevir) taken orally once daily for 16 weeks; AND
  • Prescribed by or in consultation with a hepatologist, gastroenterologist, or infectious disease (ID) specialist; AND
  • Medical records (e.g., chart notes, laboratory values) document ONE of the following:
    • Patient is treatment-naive
    • Patient has prior treatment failure with peginterferon alfa plus ribavirin
    • Patient has prior treatment failure with peginterferon alfa plus ribavirin with an NS3/4A protease inhibitor (e.g., boceprevir, simeprevir, or telaprevir); AND
  • Medical records (e.g., chart notes, laboratory values) document ALL of the following:
    • HCV genotype 1a
    • Detectable serum HCV RNA level by quantitative assay in the last 6 months
    • Patient does not have moderate to severe hepatic impairment (i.e., does not have Child-Pugh class B or class C);
    • Patient has tested positive for a baseline NS5A resistance-associated polymorphism (i.e., polymorphisms at amino acid positions 28, 30, 31 or 93); AND
  • Will be used in combination with ribavirin; AND
  • Patient is not receiving Zepatier in combination with another HCV direct-acting antiviral agent (e.g., inhibitors of the NS3/4A protease, the NS5A protein, or the NS5B polymerase); AND
  • Patient has a contraindication (e.g., safety concerns, not indicated for patient's age/weight) or intolerance to BOTH of the following:
    • Brand Epclusa (sofosbuvir/velpatasvir) OR brand Harvoni (ledipasvir/sofosbuvir)
    • Mavyret (glecaprevir/pibrentasvir)

3. Request for treatment of chronic HCV, genotype 1b, treatment-naïve or treatment-experienced to peginterferon/ribavirin with or without an NS3/4A protease inhibitor (12 weeks):

  • Dose does not exceed one tablet (50 mg or elbasvir and 100 mg of grazoprevir) taken orally once daily for 12 weeks; AND
  • Prescribed by or in consultation with a hepatologist, gastroenterologist, or infectious disease (ID) specialist; AND
  • Medical records (e.g., chart notes, laboratory values) document ONE of the following:
    • Patient is treatment-naive
    • Patient has prior treatment failure with peginterferon alfa plus ribavirin
    • Patient has prior treatment failure with peginterferon alfa plus ribavirin with an HCV NS3/4A protease inhibitor (e.g., boceprevir, simeprevir, or telaprevir); AND
  • Medical records (e.g., chart notes, laboratory values) document ALL of the following:
    • HCV genotype 1b
    • Detectable serum HCV RNA level by quantitative assay in the last 6 months
    • Patient does not have moderate to severe hepatic impairment (i.e., does not have Child-Pugh class B or class C); AND
  • Patient is not receiving Zepatier in combination with another HCV direct-acting antiviral agent (e.g., inhibitors of the NS3/4A protease, the NS5A protein, or the NS5B polymerase); AND
  • Patient has a contraindication (e.g., safety concerns, not indicated for patient's age/weight) or intolerance to BOTH of the following:
    • Brand Epclusa (sofosbuvir/velpatasvir) OR brand Harvoni (ledipasvir/sofosbuvir)
    • Mavyret (glecaprevir/pibrentasvir); AND
  • For patients with prior treatment failure with peginterferon alfa plus ribavirin plus an HCV NS3/4A protease inhibitor (e.g., boceprevir, simeprevir, or telaprevir) only: Will be used in combination with ribavirin.

4. Request for treatment of chronic HCV, genotype 4, treatment-naïve (12 weeks):

  • Dose does not exceed one tablet (50 mg or elbasvir and 100 mg of grazoprevir) taken orally once daily for 12 weeks; AND
  • Prescribed by or in consultation with a hepatologist, gastroenterologist, or infectious disease (ID) specialist; AND
  • Medical records (e.g., chart notes, laboratory values) document ALL of the following:
    • Patient is treatment-naive
    • HCV genotype 4
    • Detectable serum HCV RNA level by quantitative assay in the last 6 months
    • Patient does not have moderate to severe hepatic impairment (i.e., does not have Child-Pugh class B or class C); AND
  • Patient is not receiving Zepatier in combination with another HCV direct-acting antiviral agent (e.g., inhibitors of the NS3/4A protease, the NS5A protein, or the NS5B polymerase); AND
  • Patient has a contraindication (e.g., safety concerns, not indicated for patient's age/weight) or intolerance to BOTH of the following:
    • Brand Epclusa (sofosbuvir/velpatasvir) OR brand Harvoni (ledipasvir/sofosbuvir)
    • Mavyret (glecaprevir/pibrentasvir)

5. Request for treatment of chronic HCV, genotype 4, treatment-experienced to peginterferon/ribavirin (16 weeks):

  • Dose does not exceed one tablet (50 mg or elbasvir and 100 mg of grazoprevir) taken orally once daily for 16 weeks; AND
  • Prescribed by or in consultation with a hepatologist, gastroenterologist, or infectious disease (ID) specialist; AND
  • Medical records (e.g., chart notes, laboratory values) document ALL of the following:
    • Patient has prior treatment failure with peginterferon alfa plus ribavirin
    • HCV genotype 4
    • Detectable serum HCV RNA level by quantitative assay in the last 6 months
    • Patient does not have moderate to severe hepatic impairment (i.e., does not have Child-Pugh class B or class C); AND
  • Patient will not receive Zepatier in combination with another HCV direct-acting antiviral agent (e.g., inhibitors of the NS3/4A protease, the NS5A protein, or the NS5B polymerase); AND
  • Patient has a contraindication (e.g., safety concerns, not indicated for patient's age/weight) or intolerance to BOTH of the following:
    • Brand Epclusa (sofosbuvir/velpatasvir) OR brand Harvoni (ledipasvir/sofosbuvir)
    • Mavyret (glecaprevir/pibrentasvir)
Coverage Duration:

  • 12 weeks or 16 weeks as determined to be medically necessary (see above).

Authorization is not covered for the following:

  • The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:
  • Resistance testing: NS5A RAS testing is recommended for genotype 1a-infected, treatment naïve or experienced patients being considered for Zepatier.
  • Child-Pugh (CP) score calculation = sum of points from 5 categories:
    • Encephalopathy: None = 1 point; Grade 1 and 2 = 2 points; Grade 3 and 4 = 3 points
    • Ascites:  None = 1 point; slight = 2 points; moderate = 3 points
    • Bilirubin: under 2 mg/ml = 1 point; 2 to 3 mg/ml = 2 points; over 3 mg/ml = 3 points
    • Albumin: greater than 3.5mg/ml = 1 point; 2.8 to 3.5mg/ml = 2 points; less than 2.8mg/ml = 3 points
    • Prothrombin Time* (sec prolonged): less than 4 sec = 1 point; 4 to 6 sec = 2 points; over 6 sec = 3 points
  • Severity of cirrhosis classification using Child-Pugh (CP) calculation:
    • Child-Pugh A: 5 to 6 points - good hepatic function
    • Child-Pugh B: 7 to 9 points - moderately impaired hepatic function
    • Child-Pugh C: 10 to 15 points - advanced hepatic dysfunction
  • Examples of NS5A protein inhibitors include:
    • daclatasvir (Daklinza)
    • elbasvir (component of Zepatier)
    • ledipasvir (component of Harvoni)
    • ombitasvir (component of Viekira Pak)
    • pibrentasvir (component of Mavyret)
    • velpatasvir (component of Epclusa, component of Vosevi).
  • Examples of NS3/4A protease inhibitors include:
    • glecaprevir (component of Mavyret)
    • grazoprevir (component of Zepatier)
    • paritaprevir (component of Viekira Pak)
    • simeprevir (Olysio)
    • voxilaprevir (component of Vosevi)
    • boceprevir (Victrelis)
    • telaprevir (Incivek)
  • Examples of NS5B polymerase inhibitors include:
    • sofosbuvir (Sovaldi, component of Harvoni, component of Epclusa, component of Vosevi)
    • dasabuvir (component of Technivie)
Policy Updates:
  • 09/12/2018 – Criteria reviewed.
  • 02/15/2022 – Updated policy approved by P&T.
  • 05/17/2022 - Updated indication presented to P&T committee for patients 12yrs of age and older or weighing at least 30kg. No changes made to criteria. Updated format.
References:
  1. Tsoris A, Marlar CA. Use of the Child-Pugh Score in Liver Disease. [Updated 2021 Mar 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542308/
  2. Zepatier Prescribing Information. Merck & Co., Inc. Whitehouse Station, NJ. April 2022.
  3. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. Recommendations for Testing, Managing, and Treating Hepatitis C. September 2021. http://www.hcvguidelines.org/full-report-view. Accessed January 02, 2022.

Last review date: May 17, 2022