EPCLUSA, Sofosbuvir-Velpatasvir Form

Sofosbuvir/velpatasvir (Epclusa®) is a combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A inhibitor. ____ *These criteria do NOT apply to California Commercial Exchange Plans. FDA Approved Indication(s) Epclusa is indicated for the treatment of adult and pediatric patients 3 years of age and older with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection: • Without cirrhosis or with compensated cirrhosis
• With decompensated 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 Epclusa 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, 2, 3, 4, 5 or 6; *Chart note documentation and copies of lab results are required
3. For genotype 3: One of the following (a or b): a. Laboratory testing for the presence or absence of NS5A resistance-associated substitution (RAS) Y93H for velpatasvir if member meets one of the following scenarios (i and ii): i. Member is treatment-naïve and has cirrhosis; ii. Member has had previous HCV treatment and has no cirrhosis; b. Member does not meet one of the above scenarios in 3a;

4. 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; b. For all other requests, member must use brand version of Epclusa, unless contraindicated or clinically significant adverse effects are experienced; Page 1 of 9

   CLINICAL POLICY Sofosbuvir/Velpatasvir

5. Documentation of the treatment status of the member (treatment-naive or treatment- experienced);
6. Documentation of cirrhosis status of the member (no cirrhosis, compensated cirrhosis, or decompensated cirrhosis);
7. 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);
8. Age ≥ 3 years;
   9. Life expectancy ≥ 12 months with HCV treatment;
   10. Member agrees to participate in a medication adherence program meeting 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;
9. Prescribed regimen is consistent with an FDA or AASLD-IDSA recommended regimen (see Section V Dosage and Administration for reference);
10. Dose does not exceed one of the following (a, b, or c): a. Adult and pediatric members with body weight ≥ 30 kg: sofosbuvir/velpatasvir 400 mg/100 mg (1 tablet) per day; b. Pediatric members 3 years of age and older with body weight < 17 kg: sofosbuvir/velpatasvir 150 mg/37.5 mg per day; c. Pediatric members 3 years of age and older with body weight 17 kg to < 30 kg: sofosbuvir/velpatasvir 200 mg/50 mg per day. Approval duration: up to a total of 24 weeks (Approved duration should be consistent with a regimen in Section V Dosage and Administration) B. Other diagnoses/indications (must meet all):
    1. Member meets 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; b. For all other requests, member must use brand version of Epclusa, unless contraindicated or clinically significant adverse effects are experienced;

11. Must meet one of the following (a or b): a. 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 (i or ii): i. 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 ii. 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 b. 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.
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    CLINICAL POLICY Sofosbuvir/Velpatasvir
    II. Continued Therapy A. Chronic Hepatitis C Infection (must meet all):

12. 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. Documentation supports that member is currently receiving Epclusa for chronic HCV infection and has recently completed at least 60 days of treatment with Epclusa;
13. Member is responding positively to therapy;
    3. Dose does not exceed one of the following (a, b, or c): a. Adult and pediatric members with body weight ≥ 30 kg: sofosbuvir/velpatasvir 400 mg/100 mg (1 tablet) per day; b. Pediatric members 3 years of age and older and body weight < 17 kg: sofosbuvir/velpatasvir 150 mg/37.5 mg per day; c. Pediatric members 3 years of age and older and body weight 17 kg to < 30 kg: sofosbuvir/velpatasvir 200 mg/50 mg per day. Approval duration: up to a total of 24 weeks (Approved duration should be consistent with a regimen in Section V Dosage and Administration) B. Other diagnoses/indications (must meet all):
14. Member meets 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; b. For all other requests, member must use brand version of Epclusa, unless contraindicated or clinically significant adverse effects are experienced;

15. Must meet one of the following (a or b): a. 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 (i or ii): i. 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 ii. 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 b. 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.
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    CLINICAL POLICY Sofosbuvir/Velpatasvir
    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 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 Appendix B: Therapeutic Alternatives Not applicable IDSA: Infectious Diseases Society of America NS3/4A, NS5A/B: nonstructural protein
    PegIFN: pegylated interferon RBV: ribavirin RAS: resistance-associated substitution RNA: ribonucleic acid Appendix C: Contraindications/Boxed Warnings • Contraindication(s): Epclusa and RBV combination regimen is contraindicated in patients for whom RBV is contraindicated. Refer to the RBV prescribing information for a list of contraindications for RBV. • 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 Epclusa Harvoni Mavyret Sovaldi Viekira Pak Vosevi Zepatier *Combination drugs Velpatasvir Ledipasvir Pibrentasvir Ombitasvir Velpatasvir Elbasvir Sofosbuvir Sofosbuvir Glecaprevir Dasabuvir Paritaprevir Ritonavir Voxilaprevir Grazoprevir Appendix E: General Information • 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 Page 4 of 9

    CLINICAL POLICY Sofosbuvir/Velpatasvir
    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. • 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 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. • 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 1-6: Without cirrhosis or with compensated cirrhosis, treatment-naïve or treatment-experienced* patient Genotype 1-6:
    With decompensated cirrhosis treatment-naïve Dosing Regimen One tablet PO QD for 12 weeks One tablet PO QD with weight-based RBV for 12 weeks Maximum Dose Adult/Peds ≥ 30 kg: sofosbuvir 400 mg /velpatasvir 100 mg (one tablet) per day;
    Peds 17 to < 30 kg: sofosbuvir 200 mg /velpatasvir 50 mg per day;
    Reference FDA-approved labeling Page 5 of 9

    CLINICAL POLICY Sofosbuvir/Velpatasvir
    Indication or treatment- experienced patient Genotype 1-6: Treatment-naïve and treatment-experienced patients, post-liver transplant with compensated cirrhosis or without cirrhosis
    Genotype 1-6:
    With decompensated cirrhosis in whom prior sofosbuvir- or NS5A inhibitor-based treatment experienced failed Genotype 1-6: Treatment-naïve and treatment-experienced patients, post-liver transplant with decompensated cirrhosis Dosing Regimen (RBV-ineligible patients patients may use: one tablet PO QD for 24 weeks)ǂ One tablet PO QD for 12 weeks Maximum Dose Reference Peds < 17 kg: sofosbuvir 150 mg /velpatasvir 37.5 mg per day
    One tablet PO QD with weight-based RBV for 24 weeksǂ One tablet (sofosbuvir 400mg /velpatasvir 100
    mg) per day AASLD-IDSA (updated September 2021) One tablet (sofosbuvir 400mg /velpatasvir 100
    mg) per day AASLD-IDSA (updated September 2021) One tablet PO QD with RBV (starting at 600 mg and increased as tolerated) for 12 weeks (treatment naïve) or 24 weeks (treatment experienced)ǂ One tablet PO QD with weight-based RBV for 12 weeksǂ Genotype 3 with NS5A Y93H polymorphism: Treatment-naïve with compensated cirrhosis or treatment-experienced without cirrhosis patient 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. *From clinical trials, treatment-experienced refers to previous treatment with NS3/4A protease inhibitor (telaprevir, boceprevir, or simeprevir) and/or peginterferon/RBV unless otherwise stated
    ǂ Off-label, AASLD-IDSA guideline-supported dosing regimen One tablet (sofosbuvir 400mg /velpatasvir 100
    mg) per day AASLD-IDSA (updated September 2021) VI. Product Availability • Tablets: sofosbuvir 400 mg with velpatasvir 100 mg, sofosbuvir 200 mg with velpatasvir 50 mg • Oral pellets: sofosbuvir 200 mg with velpatasvir 50 mg, sofosbuvir 150 mg with velpatasvir 37.5 mg VII.