Hepatitis C Prior Authorization Policy Line of Business: Medi-Cal P&T Approval Date: November 15, 2017 Effective Date: January 1, 2018 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. Drugs Requiring Prior Authorization Review: Daklinza (daclatasvir), Epclusa (velpatasvir, sofosbuvir), Harvoni (ledipasvir, sofosbuvir), Mavyret (glecaprevir, pibrentasvir), Olysio (simeprevir), Pegasys (peginterferon alfa-2a), Ribavirin, Sovaldi (sofosbuvir), Viekira XR (dasabuvir, ombitasivir, paritaprevir, ritonavir), Vosevi (sofosbuvir, velpatasvir, voxilaprevir), Zepatier (elbasvir, grazoprevir) Formulary Alternatives: None Policy/Criteria: A. Drug: Mavyret (glecaprevir/pibrentasvir) Diagnosis: a. Chronic hepatitis C Specialist: a. IEHP Hepatitis Center of Excellence specialist Criteria: a. Age 18 years of age or older; b. Confirmed diagnosis of chronic hepatitis C and genotype; c. Documented baseline quantitative HCV RNA test; d. Must meet treatment criteria in Section I: Identifying treatment candidates; i. If debilitating fatigue is the only treatment criteria, IEHP clinical pharmacist review required.
e. Requested drug must be used in an antiviral treatment regimen and duration recommended by the AASLD (please see Section II: HCV Treatment Regimen). Re-authorization Criteria: a. 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. Formulary Status: Non-formulary preferred, PA applies B. Drug: Harvoni (ledipasvir/sofosbuvir) Diagnosis: a. Chronic hepatitis C Specialist: a. IEHP Hepatitis Center of Excellence specialist Criteria: a. Age 18 years of age or older; b. Confirmed diagnosis of chronic hepatitis C and genotype; c. Documented baseline quantitative HCV RNA test; d. Must meet treatment criteria in Section I: Identifying treatment candidates; i. If debilitating fatigue is the only treatment criteria, IEHP clinical pharmacist review required. e. Requested drug must be used in an antiviral treatment regimen and duration recommended by the AASLD (please see Section II: HCV Treatment Regimen). i. For genotype 1 treatment for naïve patients without cirrhosis, 8 week duration is recommended for members who meet all of the following criteria: 1. Non-black 2. HIV-uninfected 3. HCV RNA level is <6 million IU/mL f. Failure, contraindication, clinically significant adverse effects to preferred agents: Mavyret. Requests will be reviewed by IEHP pharmacist. Re-authorization Criteria: a. 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.
Formulary Status: Non-formulary, PA applies C. Drugs: Daklinza (daclatasvir), Epclusa (velpatasvir/sofosbuvir), Olysio (simeprevir), Pegasys (peginterferon alfa-2a), Sovaldi (sofosbuvir), Viekira XR (dasabuvir/ombitasivir/paritaprevir/ ritonavir), Vosevi (sofosbuvir/velpatasvir/voxilaprevir), Zepatier (elbasvir/grazoprevir) Diagnosis: a. Chronic hepatitis C Specialist: a. IEHP Hepatitis Center of Excellence specialist Criteria: a. Age 18 years of age or older; b. Confirmed diagnosis of chronic hepatitis C and genotype; c. Documented baseline quantitative HCV RNA test; d. Must meet treatment criteria in Section I: Identifying treatment candidates; i. If debilitating fatigue is the only treatment criteria, IEHP clinical pharmacist review required. e. Requested drug must be used in an antiviral treatment regimen and duration recommended by the AASLD (please see Section II: HCV Treatment Regimen); f. Failure, contraindication, clinically significant adverse effects to preferred agents: Mavyret. Requests will be reviewed by IEHP pharmacist. Re-authorization Criteria: a. 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. Formulary Status: Non-formulary, PA applies Section 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 7.1 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.
Section II: HCV Treatment Regimen (AASLD Recommendation) Treatment History and HCV Genotype Cirrhosis status Regimen Regimen Duration (GT) Bolded = Non-Formulary Preferred Hepatitis C Drug Regimen Naïve GT 1a 8 weeks, non-black, HIVuninfected, HCV RNA level <6 million IU/mL (No baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV (Baseline high fold-change NS5A RAVs for elbasvir are detected) (No baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV (Baseline high fold-change NS5A RAVs for elbasvir are detected) 8 weeks 16 weeks 16 weeks Naïve GT 1b 8 weeks, non-black, HIVuninfected, HCV RNA level 8 weeks
<6 million IU/mL Sofosbuvir/velpatasvir 400/100 mg Sofosbuvir/velpatasvir 400/100 mg Experienced GT 1a (failed PEG-IFN and RBV treatment) 8 weeks Sofosbuvir/velpatasvir 400/100 mg (No baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV (Baseline high fold-change NS5A RAVs for elbasvir are detected) Sofosbuvir/velpatasvir 400/100 mg (No baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV (Baseline high fold-change NS5A RAVs for elbasvir are detected) 16 weeks 16 weeks Experienced GT 1b (failed PEG-IFN and RBV treatment) 8 weeks
Experienced GT 1a/1b (failed NS3 Protease Inhibitor {telaprevir, boceprevir or simeprevir} + PEG- IFN + RBV) Sofosbuvir/velpatasvir 400/100 mg Experienced GT 1a/1b (failed non-ns5a inhibitor, sofosbuvir containing regimen) and Sofosbuvir/velpatasvir/voxilaprevir 400/100/100mg (for genotype 1a) (for genotype 1b) Experienced GT 1a/1b (failed NS5A inhibitor DAA) and Sofosbuvir/velpatasvir/voxilaprevir 400/100/100mg Naïve GT2 8 weeks Cirrhosis Experienced GT2 (failed PEG-IFN and RBV) 8 weeks
Experienced GT2 (failed sofosbuvir + RBV) and Naïve GT3 8 weeks Experienced GT3 (failed PEG-IFN and RBV) + sofosbuvir 400mg Experienced GT3 (failed DAA experienced, including NS5A inhibitors) and Sofosbuvir/velpatasvir/voxilaprevir 400/100/100mg Sofosbuvir/velpatasvir/voxilaprevir 400/100/100mg + RBV (for prior NS5S inhibitor failure and cirrhosis) Naïve GT4 8 weeks Experienced GT4 (failed PEG-IFN and RBV) 8 weeks
Experienced GT4 (failed DAA experienced, including NS5A inhibitors) and Sofosbuvir/velpatasvir/voxilaprevir 400/100/100mg Naïve GT 5 or 6 8 weeks Experienced GT5 or GT 6 (failed PEG-IFN and RBV) 8 weeks Experienced GT4 (DAA experienced, including NS5A inhibitors) and Sofosbuvir/velpatasvir/voxilaprevir 400/100/100mg Clinical Justification: 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. OLYSIO [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP; 2013. 15. Sovaldi [package insert]. Foster City, CA: Gilead Sciences Inc.; 2013. 16. 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 17. 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. 18. 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. 19. 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. 20. 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. 21. 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]
22. 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. 23. 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. 24. 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. 25. 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. 26. Janssen Therapeutics. Simeprevir [package insert]. 2013. Titusville, NJ, Janssen Therapeutics. 27. 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. 28. 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. 29. Zeuzem S, Dusheiko GM, Salupere R. Sofosbuvir + ribavirin for 12 or 24 weeks 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. 30. 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. 31. 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. 32. 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. 33. California Department of Health Care Services Utilization and Treatment Policy for Simeprevir and Sofosbuvir in the Management of Hepatitis C. 34. California Department of Health Care Services Treatment Policy for the Management of Chronic Hepatitis C. 35. Gilead Sciences. Epclusa [package insert]. 2016. Foster City, CA, Gilead Sciences, Inc. 36. Gilead Sciences: Vosevi [package insert]. 2017. Foster City, CA, Gilead Sciences, Inc. 37. AbbVie: Mavyret [package insert]. 2017. North Chicago, IL, AbbVie Inc.
Change Control Date Change 08/16/2017 Added Harvoni as NF Preferred to the Medi-Cal Formulary (at parity with Epclusa) 11/15/2017 Document format updated AASLD updated with new drugs added: Mavyret and Vosevi Removed all alternative regimens as first line recommended treatments are available for all genotypes Mavyret is now the preferred agent due to shorter duration of therapy and pan-genotypic coverage Vosevi added as one of the recommended regimens for treatment experienced patients Added additional guidance; if debilitating fatigue is the only indication for treatment, IEHP clinical pharmacist review is required.