Drug Class Monograph Class: Chronic Hepatitis C Drugs(s): Daclatasvir (Daklinza), Dasabuvir/ombitasivir/paritaprevir/ritonavir (Viekira XR), Elbasvir/grazoprevir (Zepatier), Peginterferon alfa-2a (Pegasys), Ledipasvir/sofosbuvir (Harvoni), Ribavirin, Simeprevir (Olysio), Sofosbuvir (Sovaldi), Velpatasvir/sofosbuvir (Epclusa) Line of Business: Non-Medicare Effective Date: November 16, 2016 Revision Date: November 16, 2016 This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutics Subcommittee. Policy/Criteria: 1. Epclusa (velpatasvir/sofosbuvir), Zepatier (elbasvir/grazoprevir) a. Must meet all of the following: i. Age 18 years of age or older; ii. Confirmed diagnosis of Hepatitis C and genotype; iii. Prescribed by IEHP Hepatitis Center of Excellence specialist; iv. Documented baseline quantitative HCV RNA test; v. Must meet treatment criteria in Section I: Identifying treatment candidates; vi. Requested drug must be used in an antiviral treatment regimen and duration recommended by the AASLD (please see Section II: HCV Treatment Regimen); vii. Re-treatment request with history of failing to achieve a SVR, or relapse after achieving a SVR with a prior completed treatment regimen consisting of Sovaldi or Harvoni, will be reviewed by IEHP pharmacist in accordance to the AASLD recommendations. 2. Viekira XR (dasabuvir/ombitasivir/paritaprevir/ritonavir) a. Must meet all of the following: i. Age 18 years of age or older; ii. Confirmed diagnosis of Hepatitis C and genotype 1a; iii. Documentation that member is treatment experienced (e.g. refractory to previous HCV therapy);
iv. Documented significant drug-drug interaction with medical justification why preferred agents (Epclusa and Zepatier) cannot be used; v. Prescribed by IEHP Hepatitis Center of Excellence specialist; vi. Documented baseline quantitative HCV RNA test; vii. Must meet treatment criteria in Section I: Identifying treatment candidates; viii. Requested drug must be used in an antiviral treatment regimen and duration recommended by the AASLD (please see Section II: HCV Treatment Regimen); ix. Re-treatment request with history of failing to achieve a SVR, or relapse after achieving a SVR with a prior completed treatment regimen consisting of Sovaldi or Harvoni, will be reviewed by IEHP pharmacist in accordance to the AASLD recommendations. 3. Harvoni (ledipasvir/sofosbuvir) a. Must meet all of the following: i. Age 18 years of age or older; ii. Confirmed diagnosis of Hepatitis C and genotype; iii. Prescribed by IEHP Hepatitis Center of Excellence specialist; iv. Documented baseline quantitative HCV RNA test; v. Must meet treatment criteria in Section I: Identifying treatment candidates; vi. Requested drug must be used in an antiviral treatment regimen and duration recommended by the AASLD (please see Section II: HCV Treatment Regimen); vii. One of the following: 1. Documentation of HIV co-infection, and receiving concomitant HIV drug therapy; 2. Documented significant drug-drug interaction with medical justification why preferred agents (Epclusa and Zepatier) cannot be used; viii. Re-treatment request with history of failing to achieve a SVR, or relapse after achieving a SVR with a prior completed treatment regimen consisting of Sovaldi or Harvoni, will be reviewed by IEHP pharmacist in accordance to the AASLD recommendations. 4. Daklinza (daclatasvir), Olysio (simeprevir), Pegasys (peginterferon alfa-2a), Sovaldi (sofosbuvir) a. Must meet all of the following: i. Age 18 years of age or older; ii. Confirmed diagnosis of Hepatitis C and genotype; iii. Prescribed by IEHP Hepatitis Center of Excellence specialist; iv. Documented baseline quantitative HCV RNA test; v. Must meet treatment criteria in Section I: Identifying treatment candidates; vi. Requested drug must be used in an antiviral treatment regimen and duration recommended by the AASLD (please see Section II: HCV Treatment Regimen);
vii. Failure, contraindication, clinically significant adverse effects to preferred agents (Epclusa, Zepatier and Harvoni). Requests will be reviewed by IEHP pharmacist; viii. Re-treatment request with history of failing to achieve a SVR, or relapse after achieving a SVR with a prior completed treatment regimen consisting of Sovaldi or Harvoni, will be reviewed by IEHP pharmacist in accordance to the AASLD recommendations. I. Identifying Treatment Candidates A. Any of the following clinical states identify candidates for treatment: 1. Evidence of Stage 2 or greater hepatic fibrosis/cirrhosis including one of the following: Liver biopsy confirming a METAVIR score F2 or greater; OR Transient elastography (Fibroscan ) score greater than or equal to 7.5 kpa; OR FibroSure score of greater than or equal to 0.48; OR APRI score greater than 0.7 OR FIB-4 greater than 3.25. 2. Evidence of extra-hepatic manifestation of hepatitis C virus, such as type 2 or 3 essential mixed cryoglobulinemia with end- organ manifestations (e.g. vasculitis), or kidney disease (e.g. proteinuria, nephrotic syndrome or membranoproliferative glomerulonephritis). 3. Persons with hepatocellular carcinoma with a life expectancy of greater than 12 months; 4. Pre- and post-liver transplant, or other solid organ transplant; 5. HIV-1 co-infection; 6. Hepatitis B co-infection; 7. Other coexistent liver disease (e.g. nonalcoholic steatohepatitis); 8. Type 2 diabetes mellitus (insulin resistant); 9. Porphyria cutanea tarda; 10. Debilitating fatigue impacting quality of life (e.g., secondary to extra-hepatic manifestations and/or liver disease); 11. Men who have sex with men with high-risk sexual practices; 12. Active injection drug users; 13. Persons on long-term hemodialysis; 14. Women of childbearing age who wish to get pregnant; 15. HCV-infected health care workers who perform exposure-prone procedures; B. Patient Readiness and Adherence: 1. Patients shall be evaluated for readiness to initiate treatment. 2. Patients selected for treatment shall be able and willing to strictly adhere to treatment protocols prescribed by their provider. 3. Caution shall be exercised with patients who have a history of treatment failure with prior hepatitis C treatment due to non-adherence with treatment regimen and appointments. Patients shall be educated regarding potential risks and benefits of hepatitis C virus therapy,
as well as the potential for resistance and failed therapy if medication is not taken as prescribed. C. Age requirements: Treatment candidate must be 18 years of age or older. D. Populations Unlikely to Benefit from Hepatitis C Virus Treatment: According to AASLD/IDSA hepatitis C virus Guidelines, patients with limited life expectancy for whom hepatitis C virus therapy would not improve symptoms or prognosis do not require treatment. Chronic hepatitis C is associated with a wide range of comorbid conditions. Little evidence exists to support initiation of hepatitis C virus treatment in patients with limited life expectancy (less than 12 months) due to non liver-related comorbid conditions. For these patients, the benefits of hepatitis C virus treatment are unlikely to be realized, and palliative care strategies should take precedence. In patients with a life expectancy less than 12 months, treatment is not recommended. II. HCV Treatment Regimen (AASLD Recommendation) Treatment History Regimen and HCV Genotype (GT) Bolded = Non-Formulary Preferred Hepatitis C Drug Regimen Naïve GT 1a Non- (No baseline high fold-change NS5A Regimen Duration Sofosbuvir + velpatasvir 400/100mg (Baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV Sofosbuvir + simeprevir 400/150mg Daclatasvir/sofosbuvir 60/400mg
Compensated ) (No baseline high fold-change NS5A Sofosbuvir + velpatasvir 400/100mg (Baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV Sofosbuvir + simeprevir 400/150mg ± RBV (Member must be screened and is negative for the NS3Q80K polymorphism) Naïve GT 1b Non- Sofosbuvir/velpatasvir 400/100 mg Compensated ) 150/100/25mg + dasabuvir 250mg bid Sofosbuvir + simeprevir 400/150mg Daclatasvir/sofosbuvir 60/400mg Sofosbuvir/velpatasvir 400/100 mg Sofosbuvir + simeprevir 400/150mg ± RBV
Experienced GT 1a (failed PEG-IFN and RBV treatment) Non- Sofosbuvir/velpatasvir 400/100 mg (No baseline high fold-change NS5A (Baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV Sofosbuvir + simeprevir 400/150mg Daclatasvir/sofosbuvir 60/400mg Compensated (No baseline high fold-change NS5A Sofosbuvir/velpatasvir 400/100 mg + RBV (Baseline high fold-change NS5A RAVs for elbasvir are detected) ) + RBV Sofosbuvir/simeprevir 400/150mg ± RBV (Member must be screened and is negative for the NS3Q80K polymorphism)
Experienced GT 1b (failed PEG-IFN and RBV treatment) Non- Sofosbuvir/velpastavir 400/100mg Sofosbuvir/simeprevir 400/150mg Daclatasvir/sofosbuvir 60/400mg Compensated Sofosbuvir/velpastavir 400/100mg + RBV Experienced GT 1a/1b (failed Sofosbuvir and RBV with or without PEG-IFN) Experienced GT 1a/1b (failed NS3 Protease Inhibitor {telaprevir, boceprevir or simeprevir} treatment + PEG- IFN/RBV) ) Sofosbuvir/simeprevir 400/150mg ± RBV Non- + RBV Compensated + RBV Non- Sofosbuvir/velpatasvir 400/100 mg (No baseline high fold-change NS5A (GT1a: Baseline high fold-change NS5A Daclatasvir/sofosbuvir 60/400mg
Compensated Sofosbuvir/velpastavir 400/100mg (No baseline high fold-change NS5A + RBV (GT1a: Baseline high fold-change NS5A Experienced GT 1a/1b (failed simeprevir + sofosbuvir ) or (failed HCV NS5A inhibitor) Non- Deferral of treatment is recommended, pending availability of data Testing for resistance-associated variants that confer decreased susceptibility to NS3 protease inhibitor and to NS5A inhibitors is recommended Please refer to AASLD guideline -- May consider nucleotide-based triple or quadruple DAA regimens + RBV (unless RBV is contraindicated) Nucleotide-based dual DAA therapy + RBV (unless RBV is contraindicated) -- 12-24 weeks Naïve GT2 Non- Sofosbuvir/velpatasvir 400/100mg (non-) Daclatasvir/sofosbuvir 60/400mg Experienced GT2 (failed PEG- IFN/RBV) Compensated Sofosbuvir/velpatasvir 400/100mg Cirrhosis ) Daclatasvir/sofosbuvir 60/400mg 16-24 weeks Non- Sofosbuvir/velpastavir 400/100mg Daclatasvir/sofosbuvir 60/400mg (non-) Compensated Sofosbuvir/velpastavir 400/100mg Daclatasvir/sofosbuvir 60/400mg 16 24
Experienced GT2 (failed sofosbuvir + RBV) ) Regardless of status Sofosbuvir/velpastavir 400/100mg + RBV weeks Naïve GT3 Non- Sofosbuvir/velpatasvir 400/100mg Compensated Sofosbuvir/velpatasvir 400/100mg Experienced GT3 (failed IFN+RBV) Non- Sofosbuvir/velpatasvir 400/100mg Compensated Sofosbuvir/velpatasvir 400/100mg + RBV Daclatasvir/sofosbuvir 60/400mg + RBV Experienced GT3 (failed sofosbuvir + RBV) Regardless of status Daclatasvir/sofosbuvir 60/400mg + RBV Sofosbuvir/velpatasvir 400/100mg+RBV Naïve GT4 Regardless of status Sofosbuvir/velpastavir 400/100mg Experienced GT4 (failed PEG- IFN+RBV) Non- 150/100/25mg + RBV Sofosbuvir/velpastavir 400/100mg Compensated 150/100/25mg + RBV (prior on-treatment virologic failure failure to suppress or breakthrough Sofosbuvir/velpastavir 400/100mg
+ RBV Naïve GT 5 or 6 ) Regardless of status 150/100/25mg + RBV (prior on-treatment virologic failure failure to suppress or breakthrough Sofosbuvir/velpatasvir 400/100mg Experienced GT5 or GT 6 (failed PEG-IFN + RBV) Regardless of status Sofosbuvir/velpatasvir 400/100mg Clinical Evidence: Please refer to the American Association for the Study of Liver Diseases (AASLD) HCV Clinical Practice Guideline. References: 1. American Association for the Study of Liver Diseases. Available from: http://www.hcvguidelines.org/full-report-view 2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. J Hepatol. 2011;55(2):245-64. Epub 2011 Mar 1. 3. Poordad F. Big Changes Are Coming in Hepatitis C Curr Gastroenterol Rep 2011;13(1):72-7. 4. Hofmann WP, Zeuzem S. A new standard of care for the treatment of chronic HCV infection. Nat Rev Gastroenterol Hepatol 2011;8(5):257-64. 5. Pawlotsky JM. The Results of Phase III Clinical Trials With Telaprevir and Boceprevir Presented at the Liver Meeting 2010: A New Standard of Care for Hepatitis C Virus Genotype 1 Infection, But With Issues Still Pending. Gastroenterology. 2011;140(3):746-54. 6. Victrelis [package insert]. Whitehouse Statin, NJ: Merck & Co., Inc; 2011, 2013. Prescribing Information. 7. Poordad F, McCone J, Bacon B et al. Boceprevir for untreated chronic HCV genotype 1 infection. NEJM 2011;364:1195-1206. 8. Bacon B, Gordon S, Lawitz E et al. Boceprevir for previously treated chronic HCV genotype 1 infection. NEJM 2011;364:1207-1217. 9. Jensen DM. A new era of hepatitis C therapy begins. N Engl J Med. 2011;364(13):1272-4.
10. INCIVEK (telaprevir) Prescribing Information. 11. Jacobson I, McHutchison J, Dusheiko G, et al. Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection. N Engl J Med. 2011;364:2405-16. 12. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for Retreatment of HCV Infection. N Engl J Med. 2011;364:2417-28. 13. Jacobson, Ira. SVR results of a once-daily regimen of simeprevir (SMV, TMC435) plus sofosbuvir (SOF, GS-7977) with or without ribavirin in and non- HCV genotype 1 treatment-naïve and prior null responder patients: The COSMOS study. AASLD 2013 Nov. 14. VICTRELIS AMCP Dossier. 15. INCIVEK [telaprevir] AMCP Dossier. 16. OLYSIO [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP; 2013. 17. Sovaldi [package insert]. Foster City, CA: Gilead Sciences Inc.;2013. 18. Department of Veterans Affairs National Hepatitis C Resource Center Program and the Office of Public Health. Chronic Hepatitis C Virus (HCV) Infection: Treatment Considerations. March 27, 2014. Available from: http://www.hepatitis.va.gov/provider/guidelines/2014hcv/index.asp 19. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014a;370(20):1889-1898. 20. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888. 21. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1594-1603. 22. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370(21):1983-1992. 23. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis. N Engl J Med. 2014;[Epub ahead of print] 24. Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014a;383(9916):515-523. 25. Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet. 2014b;384(9956):1756-1765. 26. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1604-1614. 27. Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatmentexperienced patients with HCV genotype 1b infection. Gastroenterology. 2014;147(2):359-365. 28. Janssen Therapeutics. Simeprevir [package insert]. 2013.Titusville, NJ, Janssen Therapeutics. 29. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013 May 16;368(20):1878-87.
30. Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013 May 16;368(20):1867-77. 31. Zeuzem S, Dusheiko GM, Salupere R. Sofosbuvir + ribavirin for 12 or for patients with HCV genotype 2 or 3: the VALENCE trial. In: Program and abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1-5, 2013; Washington, DC. Abstract 1085. 32. Lawitz E, Poordad F, Brainard DM, et al. Sofosbuvir in combination with pegifn and ribavirin for provides high SVR rates in HCV-infected genotype 2 or 3 treatment experienced patients with and without compensated cirrhosis: results from the LONESTAR-2 study. In: Program and abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1-5, 2013; Washington, DC. Abstract LB4. 33. Sulkowski MS, Rodriguez-Torres M, Lalezari JP, et al. All-oral therapy with sofosbuvir plus ribavirin for the treatment of HCV genotype 1, 2, and 3 infection in patients co-infected with HIV (PHOTON-1). In: Program and abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases; November 1-5, 2013; Washington, DC. Abstract 212. 34. American Association for the Study of Liver Diseases. Recommendation for Testing, Managing and Treating Hepatitis C. Available at: http://www.hcvguidelines.org/full-reportview. Assessed July, 12, 2015. 35. California Department of Health Care Services Utilization and Treatment Policy for Simeprevir and Sofosbuvir in the Management of Hepatitis C. 36. California Department of Health Care Services Treatment Policy for the Management of Chronic Hepatitis C. 37. Gilead Sciences. Epclusa [package insert]. 2016. Foster City, CA, Gilead Sicences, Inc.