Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir (Viekira Pak) Form

Dasabuvir/paritaprevir/ritonavir/ombitasvir (Viekira Pak®) is a combination of ombitasvir, a hepatitis C virus (HCV) NS5A inhibitor, paritaprevir, an HCV NS3/4A protease inhibitor, ritonavir, a CYP3A inhibitor and dasabuvir, an HCV non-nucleoside NS5B palm polymerase inhibitor. ____ *These criteria do NOT apply to California Commercial Exchange Plans. FDA Approved Indication(s) Viekira Pak is indicated for the treatment of adult patients with chronic HCV: • Genotype 1b without cirrhosis or with compensated cirrhosis • Genotype 1a without cirrhosis or with compensated cirrhosis for use in combination with ribavirin (RBV) Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Viekira Pak is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Hepatitis C Infection (must meet all):

1. Diagnosis of chronic HCV infection as evidenced by detectable serum HCV RNA levels by quantitative assay in the last 6 months;
2. Confirmed HCV genotype is 1; *Chart note documentation and copies of lab results are required
3. Prescribed by or in consultation with a gastroenterologist, hepatologist or infectious disease specialist, or provider who has expertise in treating HCV based on a certified training program (see Appendix F);

4. Age ≥ 18 years;

   5. If cirrhosis is present, confirmation of Child-Pugh A status;
   6. One of the following (a or b): a. If request is from Florida, member must use Epclusa authorized generic, unless contraindicated or clinically significant adverse effects are experienced; Page 1 of 8

   CLINICAL POLICY Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir b. For all other requests, member must use Epclusa® (brand preferred), unless contraindicated or clinically significant adverse effects are experienced (see Appendix E); *Coadministration with omeprazole up to 20 mg is not considered acceptable medical justification for inability to use Epclusa

5. Life expectancy ≥ 12 months with HCV treatment;
   8. Member agrees to participate in a medication adherence program including both of the following components (a and b): a. Medication adherence monitored by pharmacy claims data or member report; b. Member’s risk for non-adherence identified by adherence program or member/prescribing physician follow-up at least every 4 weeks;
6. Prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen (see Section V Dosage and Administration for reference);
7. If HCV/HIV-1 co-infection, member is or will be on a suppressive antiretroviral drug regimen to reduce the risk of HIV-1 protease inhibitor drug resistance;
8. Dose does not exceed ombitasvir/paritaprevir/ritonavir 12.5 mg/75 mg/50 mg (2 tablets) once daily and dasabuvir 250 mg (1 tablet) twice daily. Approval duration: up to a total of 12 weeks (Approved duration should be consistent with a regimen in Section V Dosage and Administration) B. Other diagnoses/indications (must meet 1 or 2):
9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace; or
10. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace. II. Continued Therapy A. Chronic Hepatitis C Infection (must meet all):

11. Member meets one of the following (a, b, or c ): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. 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); c. Must meet both of the following (i and ii): i. Documentation supports that member is currently receiving Viekira Pak for chronic HCV infection and has recently completed at least 60 days of treatment with Viekira Pak; Page 2 of 8

    CLINICAL POLICY Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir ii. Confirmed HCV genotype is 1;

    2. Member is responding positively to therapy;
    3. Dose does not exceed ombitasvir/paritaprevir/ritonavir 12.5 mg/75 mg/50 mg (2 tablets) once daily and dasabuvir 250 mg (1 tablet) twice daily. Approval duration: up to a total of 12 weeks (Approved duration should be consistent with a regimen in Section V Dosage and Administration) B. Other diagnoses/indications (must meet 1 or 2):
12. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace; or

13. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace. III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off-label use policy – HIM.PA.154 for health insurance marketplace or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AASLD: American Association for the Study of Liver Diseases FDA: Food and Drug Administration HBV: hepatitis B virus HCV: hepatitis C virus HIV: human immunodeficiency virus IDSA: Infectious Diseases Society of America NS3/4A, NS5A/B: nonstructural protein
    PegIFN: pegylated interferon RBV: ribavirin RNA: ribonucleic acid Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Dosing Regimen Drug Name sofosbuvir/
    velpatasvir
    (Epclusa®) Treatment-naïve or treatment-experienced without cirrhosis or with compensated cirrhosis: Genotype 1 Page 3 of 8 Dose Limit/
    Maximum Dose sofosbuvir 400 mg/ velpatasvir 100 mg
    (1 tablet) per day

    CLINICAL POLICY Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir Drug Name Dosing Regimen Dose Limit/
    Maximum Dose One tablet PO QD for 12 weeks Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): Viekira Pak is contraindicated in: o Patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity o If Viekira is administered with RBV, the contraindications to RBV also apply to this combination regimen. Refer to the RBV prescribing information for a list of contraindications for RBV. o Co-administration with drugs that are:

    • Highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
    • Moderate or strong inducers of CYP3A and strong inducers of CYP2C8 and may lead to reduced efficacy of Viekira Pak.
    • Strong inhibitors of CYP2C8 and may increase dasabuvir plasma concentrations and the risk of QT prolongation. o Patients with known hypersensitivity to ritonavir (e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome). • Boxed warning(s): risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV Appendix D: Direct-Acting Antivirals for Treatment of HCV Infection Brand Name Drug Class NS5A Inhibitor NS3/4A Protease Inhibitor (PI) CYP3A Inhibitor -Non Nucleoside NS5B Palm Polymerase Inhibitor Nucleotide Analog NS5B Polymerase Inhibitor Sofosbuvir Sofosbuvir Velpatasvir Ledipasvir Pibrentasvir Epclusa Harvoni Mavyret Sovaldi Viekira Pak Ombitasvir Velpatasvir Vosevi Elbasvir Zepatier *Combination drugs Sofosbuvir Sofosbuvir Dasabuvir Glecaprevir Paritaprevir Voxilaprevir Grazoprevir Ritonavir Appendix E: General Information • Acceptable medical justification for inability to use Epclusa (preferred product): o In patients indicated for co-administration of Epclusa with ribavirin: contraindications to ribavirin. Page 4 of 8

    CLINICAL POLICY Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir o In patients indicated for co-administration with amiodarone: serious symptomatic bradycardia in patients taking amiodarone, with cardiac monitoring recommended. • Unacceptable medical justification for inability to use Epclusa (preferred product): o Coadministration with omeprazole up to 20 mg is not considered acceptable medical justification for inability to use Epclusa.
     Per the Epclusa Prescribing Information: “If it is considered medically necessary to coadminister, Epclusa should be administered with food and taken 4 hours before omeprazole 20 mg.” • HBV reactivation is a Black Box Warning for all direct-acting antiviral drugs for the treatment of HCV. HBV reactivation has been reported when treating HCV for patients co-infected with HBV, leading to fulminant hepatitis, hepatic failure, and death, in some cases. Patients should be monitored for HBV reactivation and hepatitis flare during HCV treatment and post-treatment follow-up, with treatment of HBV infection as clinically indicated. • For patients with HCV/HIV-1 (human immunodeficiency virus type-1) co-infection, the patient should be on a suppressive antiretroviral drug regimen to reduce the risk of HIV-1 protease inhibitor drug resistance. • Child-Pugh Score: Bilirubin Albumin INR Ascites 1 Point Less than 2 mg/dL Less than 34 umol/L Over 3.5 g/dL Over 35 g/L Less than 1.7 None Encephalopathy None 2 Points 2-3 mg/dL 34-50 umol/L 2.8-3.5 g/dL 28-35 g/L 1.7 - 2.2 Mild / medically controlled Mild / medically controlled Grade I-II 3 Points Over 3 mg/dL Over 50 umol/L Less than 2.8 g/dL Less than 28 g/L Over 2.2 Moderate-severe / poorly controlled Moderate-severe / poorly controlled. Grade III-IV Child-Pugh class is determined by the total number of points: A = 5-6 points; B = 7-9 points; C = 10-15 points. • The AASLD/IDSA HCV Guidance as of March 2021 carries no Viekira Pak recommendations for any genotype. Appendix F: Healthcare Provider HCV Training Acceptable HCV training programs and/or online courses include, but are not limited to the following:
    • Hepatitis C online course (https://www.hepatitisc.uw.edu/): University of Washington is funded by the Division of Viral Hepatitis to develop a comprehensive, online self-study course for medical providers on diagnosis, monitoring, and management of hepatitis C virus infection. Free CME and CNE credit available. • Fundamentals of Liver Disease (https://liverlearning.aasld.org/fundamentals-of-liver- disease): The AASLD, in collaboration with ECHO, the American College of Physicians (ACP), CDC, and the Department of Veterans Affairs, has developed Fundamentals of Liver Disease, a free, online CME course to improve providers’ knowledge and clinical skills in hepatology. Page 5 of 8

    CLINICAL POLICY Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir • Clinical Care Options: http://www.clinicaloptions.com/hepatitis.aspx • CDC training resources: https://www.cdc.gov/hepatitis/resources/professionals/trainingresources.htm V. Dosage and Administration
    Indication Genotype 1a: Treatment- naive or interferon- experienced without cirrhosis Dosing Regimen Maximum Dose Viekira Pak plus weight-based RBV for 12 weeks Viekira Pak: paritaprevir 150 mg /ritonavir 100 mg/ ombitasvir 25 mg per day; dasabuvir 500 mg per day Reference FDA-approved labeling Viekira Pak for 12 weeks Genotype 1b: Treatment- naïve or interferon- experienced with or without compensated cirrhosis AASLD/IDSA treatment guidelines for chronic hepatitis C infection are updated at irregular intervals; refer to the most updated AASLD/IDSA guideline for most accurate treatment regimen. The AASLD/IDSA HCV guidance no longer recommends use of Viekira Pak
    FDA-approved labeling VI. Product Availability • Tablet: paritaprevir 75 mg, ritonavir 50 mg, ombitasvir 12.5 mg • Tablet: dasabuvir 250 mg *Viekira Pak is dispensed in a monthly carton for a total of 28 days of therapy. Each monthly carton contains four weekly cartons. Each weekly carton contains seven daily dose packs. VII.