Chronic Hepatitis C Drug Class Monograph Line of Business: Medi-Cal Effective Date: July 10, 2017 (Interim Guidelines; Final Review and Approval by the P&T Subcommittee Pending) 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(s): Daklinza (daclatasvir), Epclusa (velpatasvir/sofosbuvir), Harvoni (ledipasvir/sofosbuvir), Olysio (simeprevir), Pegasys (peginterferon alfa-2a), Ribavirin, Sovaldi (sofosbuvir), Viekira XR (dasabuvir/ombitasivir/paritaprevir/ritonavir), Zepatier (elbasvir/grazoprevir) Policy/Criteria: 1. 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); 1. For genotype 1 treatment for naïve patients without cirrhosis, 8 week duration is recommended for non-black, HIV-uninfected and whose HCV RNA level is <6 million IU/mL. 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. Epclusa (velpatasvir/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. 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. Daklinza (daclatasvir), Olysio (simeprevir), Pegasys (peginterferon alfa-2a), Sovaldi (sofosbuvir), Viekira XR (dasabuvir/ombitasivir/paritaprevir/ritonavir), 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. Failure, contraindication, clinically significant adverse effects to preferred agents (Harvoni and Epclusa). 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 and HCV Genotype (GT) Naïve GT 1a, non-black, HIVuninfected, HCV RNA level <6 million IU/mL Regimen Bolded = Non-Formulary Preferred Hepatitis C Drug Regimen Regimen Duration 8 weeks Sofosbuvir + velpatasvir 400/100mg + RBV (Baseline high fold-change NS5A RAVs for elbasvir are detected) (No baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV Sofosbuvir + simeprevir 400/150mg Sofosbuvir + velpatasvir 400/100mg (No baseline high fold-change NS5A RAVs for elbasvir are detected)
) + 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) Naïve GT 1b, non-black, HIVuninfected, HCV RNA level <6 million IU/mL 8 weeks Sofosbuvir/velpatasvir 400/100 mg 150/100/25mg + dasabuvir 250mg bid Sofosbuvir + simeprevir 400/150mg Sofosbuvir/velpatasvir 400/100 mg Experienced GT 1a (failed PEG-IFN and RBV ) Sofosbuvir + simeprevir 400/150mg ± RBV Sofosbuvir/velpatasvir 400/100 mg
treatment) + RBV (Baseline high fold-change NS5A RAVs for elbasvir are detected) (No baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV Sofosbuvir + simeprevir 400/150mg ) + RBV 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) + 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) Sofosbuvir/velpastavir 400/100mg Sofosbuvir/simeprevir 400/150mg + RBV Sofosbuvir/velpastavir 400/100mg 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 + RBV + RBV Sofosbuvir/velpatasvir 400/100 mg + RBV (GT1a: Baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV (No baseline high fold-change NS5A RAVs for elbasvir are detected)
+ RBV Sofosbuvir/velpastavir 400/100mg + RBV (No baseline high fold-change NS5A RAVs for elbasvir are detected) + RBV (GT1a: Baseline high fold-change NS5A RAVs for elbasvir are detected) Experienced GT 1a/1b (failed simeprevir + sofosbuvir ) or (failed HCV NS5A inhibitor) 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 Sofosbuvir/velpatasvir 400/100mg (non-) Experienced GT2 (failed PEG- IFN/RBV) Sofosbuvir/velpatasvir 400/100mg Cirrhosis ) 16-24 weeks Sofosbuvir/velpastavir 400/100mg (non-) Sofosbuvir/velpastavir 400/100mg
Experienced GT2 (failed sofosbuvir + RBV) ) Regardless of status 16 24 weeks Sofosbuvir/velpastavir 400/100mg + RBV Naïve GT3 Sofosbuvir/velpatasvir 400/100mg Sofosbuvir/velpatasvir 400/100mg Experienced GT3 (failed IFN+RBV) Sofosbuvir/velpatasvir 400/100mg Sofosbuvir/velpatasvir 400/100mg + RBV + RBV Experienced GT3 (failed sofosbuvir + RBV) Regardless of status + RBV Sofosbuvir/velpatasvir 400/100mg+RBV Naïve GT4 Regardless of status Sofosbuvir/velpastavir 400/100mg Experienced GT4 (failed PEG- IFN+RBV) 150/100/25mg + RBV Sofosbuvir/velpastavir 400/100mg 150/100/25mg + RBV + RBV (prior on-treatment virologic failure failure to suppress or breakthrough + RBV
Sofosbuvir/velpastavir 400/100mg Naïve GT 5 or 6 ) Regardless of status 150/100/25mg + RBV + 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.
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