Sovaldi (sofosbuvir) GA Medicaid

Transcription

1 Sovaldi (sofosbuvir) GA Medicaid Override(s) Prior Authorization Quantity Limit Medication Sovaldi (sofosbuvir) Approval Duration Based on Genotype, Treatment status, Cirrhosis status, Hepatocellular Carcinoma status, Peginterferon Eligibility status, Q80K Polymorphism status or transplant status Quantity Limit 1 tablet per day APPROVAL DURATION Genotype and Status (HCV mono-infected or HCV/HIV-1 co-infected 1 ) Genotype 1 (treatment-naïve, with compensated cirrhosis or without cirrhosis, peginterferon ineligible) Genotype 2 (treatment-naïve, with compensated cirrhosis or without cirrhosis) Genotype 2 (dual treatment-experienced, with compensated cirrhosis or without cirrhosis) Genotype 3 (treatment-naïve or dual treatment experienced with compensated cirrhosis or without cirrhosis, peginterferon and Daklinza ineligible) Genotype 3 (post-liver allograft transplant, with decompensated cirrhosis) Hepatocellular Carcinoma awaiting liver transplant Genotype 1 (with compensated cirrhosis or without cirrhosis) Genotype 4 (treatment-naïve, with compensated cirrhosis or without cirrhosis) Genotype 1 (treatment-naïve or dual treatmentexperienced +, without cirrhosis) Genotype 1a (treatment-naïve or dual treatmentexperienced +, with compensated cirrhosis, without Q80K polymorphism) Genotype 1b (treatment-naïve or dual treatmentexperienced +, with compensated cirrhosis) Genotype 1 (treatment-naïve or -experienced #, postliver allograft transplant, with compensated cirrhosis or without cirrhosis) Genotype 1 (treatment-naïve or -experienced,, without cirrhosis) Associated Treatment Regimens Sovaldi + RBV Sovaldi + RBV Sovaldi + RBV Sovaldi + RBV Sovaldi + RBV Sovaldi + RBV Sovaldi + PEG-IFN + RBV Sovaldi + PEG-IFN + RBV Sovaldi + Olysio Sovaldi + Olysio ± RBV Sovaldi + Olysio ± RBV Sovaldi + Olysio ± RBV Sovaldi + Daklinza Total Approval Duration for Sovaldi 24 weeks 24 weeks 24 weeks Up to 48 weeks** 24 weeks 24 weeks PAGE 1 of 15 11/01/2017 WEBPGA

2 Genotype and Status (HCV mono-infected or HCV/HIV-1 co-infected 1 ) Associated Treatment Regimens Sovaldi + Daklinza ± RBV Total Approval Duration for Sovaldi Genotype 1 (treatment-naïve or -experienced,, with compensated cirrhosis) 12 or 24 weeks Genotype 2 (treatment-naïve or dual treatmentexperienced, without cirrhosis) Sovaldi + Daklinza Genotype 2 (treatment-naïve or dual treatmentexperienced, with compensated cirrhosis) Sovaldi + Daklinza 16 or 24 weeks Genotype 3 (treatment-naive or -experienced, without cirrhosis) Sovaldi + Daklinza Genotype 3 (treatment-naïve, with compensated Sovaldi + Daklinza cirrhosis) + RBV Genotype 3 (treatment-naïve, with compensated Sovaldi + Daklinza cirrhosis) ± RBV 24 weeks Genotype 3 (dual treatment-experienced, without Sovaldi + Daklinza cirrhosis) + RBV 24 weeks Genotype 3 ((dual, treatment-experienced or triple Sovaldi + Daklinza treatment-experienced, with compensated cirrhosis) + RBV 12 or 24 weeks Genotype 3 (dual treatment-experienced, without Sovaldi + Daklinza cirrhosis, with Y93H polymorphism) + RBV Genotypes 1,±, 2, 3, or 4 (treatment-naïve or -experienced Sovaldi + Daklinza, post-liver allograft transplant, with + RBV compensated cirrhosis or without cirrhosis) Genotypes 1,±, 2, 3, or 4 (treatment-naïve or Sovaldi + Daklinza -experienced with decompensated cirrhosis) + RBV Genotype 3 (treatment-experienced ϴ with or without Sovaldi + Zepatier cirrhosis) ± RBV 12 or 16 weeks Dual treatment-experienced refers to individuals who have had a partial response, no response, or prior relapse with a previous dual therapy regimen of peginterferon and ribavirin. The September 2016 AASLD/IDSA treatment guidance maintained the February 2016 omission of the previously recommended regimen of sofosbuvir and ribavirin in Genotype 3 decompensated cirrhotics post-liver transplant. The December 2015 version maintained citation of a compassionate use program conducted by Forns et al as rationale for clinical recommendation rating of Class I, Level B. **Therapy duration is recommended for up to 48 weeks or until the time of liver transplantation, whichever occurs first. + Per Olysio label, treatment-experienced includes prior dual therapy (peginterferon and ribavirin) relapsers (HCV RNA not detected at the end of prior IFN-based therapy and detected during follow-up), prior partial responders (prior on-treatment 2 log10 IU/mL reduction in HCV RNA from baseline at Week 12 and HCV RNA detected at end of prior dual therapy) or prior null responders (prior on-treatment < 2 log10 reduction in HCV RNA from baseline at Week 12 during prior dual therapy). # Per the September 2016 AASLD/IDSA treatment guidance, support for Sovaldi and Olysio combination use in the liver post-transplant population is based on retrospective (Pungpapong et al. 2015, Brown et al. 2016) and ongoing prospective (O Leary et al. 2016) studies in treatment-naïve and -experienced patients. Studies conducted in the treatment-experienced population mostly comprise prior regimens of dual therapy (peginterferon and ribavirin) or triple therapy (peginterferon; ribavirin; and Incivek, Victrelis, Olysio, or Sovaldi). The February 2016 updated Daklinza label references ALLY-1, ALLY-2, and ALLY-3 (Nelson et al. 2015) clinical trials which included treatment-experienced individuals who predominately tried and failed a prior dual therapy regimen of interferon/peginterferon and ribavirin. The clinical trials included a small subset of individuals who PAGE 2 of 15 11/01/2017

3 tried and failed a triple therapy regimen of peginterferon, ribavirin, and a NS3 HCV protease inhibitor (Incivek, Victrelis, or Olysio). The February 2016 updated Daklinza label references ALLY-1, ALLY-2, and ALLY-3 (Nelson et al. 2015) clinical trials which included a small subset of treatment-experienced individuals who tried and failed a dual therapy regimen of sofosbuvir and ribavirin. Daklinza s label recommends treatment duration of with or without ribavirin and regardless of cirrhosis status. The September 2016 AASLD/IDSA treatment guidance recommends treating for 24 weeks with or without ribavirin and regardless of cirrhosis status. The September 2016 AASLD/IDSA treatment guidance cites the Sulkowski et al clinical trial as rationale for recommending use in individuals with Genotype 1 and triple treatment-experienced defined as a prior failed trial of a NS3 HCV protease inhibitor (Incivek, Victrelis, or Olysio), peginterferon, and ribavirin. π The September 2016 AASLD/IDSA treatment guidance cites the Wyles et al (ALLY-2) and Sulkowski et al.2014 clinical trials as rationale for recommending use in Genotype 2 dual treatment-experienced (peginterferon and ribavirin). ± The September 2016 AASLD/IDSA treatment guidance cites the Poordad et al (ALLY-1) clinical trial and Foster et al cohort study as rationale for recommending use in decompensated cirrhosis and Poordad et al (ALLY-1), Herzer et al. 2015, and Fontana et al clinical trials for post-liver allograft transplant in Genotype 1. The September 2016 AASLD/IDSA treatment guidance cites the Poordad et al (ALLY-1) trial as rationale for recommending use in decompensated cirrhosis and post-liver allograft transplant in Genotypes 2 and 4. The September 2016 AASLD/IDSA treatment guidance cites the Poordad et al (ALLY-1) clinical trial, Foster et al cohort study, and Welzel et al compassionate use study as rationale for recommending use in decompensated cirrhosis and Poordad et al (ALLY-1) for post-liver allograft transplant in Genotype 3. ϴ The May 2017 AASLD/IDSA treatment guidance cites the C-ISLE study with Genotype 3 and cirrhosis who failed a dual therapy regimen (peginterferon and ribavirin). They were split into 3 arms, a small subset of 17 individuals showed 100% SVR. Also in the C-ISLE study (Foster 2016b), two individuals who failed a dual therapy regimen (sofosbuvir and ribavirin) reached SVR12. APPROVAL CRITERIA Requests for Sovaldi (sofosbuvir) may be approved if the following criteria are met: I. A copy of the baseline quantitative hepatitis C virus (HCV) RNA test result is provided to document baseline level of viremia; AND II. One of the following: A. Documentation is provided for a diagnosis of chronic hepatitis C (CHC) infection, which includes genotype 1 and a positive HCV RNA test result at least 6 months following either a baseline positive HCV RNA result or reactive HCV antibody test (AASLD/IDSA 2016, CDC 2013); B. Individual is unable to delay treatment for 6 months owing to concurrent factors [such as but not limited to, advanced liver disease (Metavir fibrosis stage of F3 or F4 2 ), post-liver transplant recipients, chronic HCV infection-associated extrahepatic manifestations (such as membranoproliferative glomerulonephritis, glomerular disease, cryoglobulinemia syndrome)] (AASLD/IDSA 2016); AND C. Documentation is provided for a diagnosis of CHC infection, which includes genotype 1 (AASLD/IDSA 2016), a reactive HCV antibody (CDC 2013), and a subsequent positive HCV RNA result (CDC 2013); AND PAGE 3 of 15 11/01/2017

4 III. Individual does not have a short life expectancy (less than 12 months owing to non-liver related comorbid conditions) that cannot be remediated by treating HCV, by transplantation or other directed therapy (AASLD/IDSA 2016); AND IV. Individual must be enrolled in a substance abuse program if there is abuse of alcohol or intravenous drugs; AND V. Individual has one of the following: A. Genotypes 1, 2, 3, 4, 5, or 6 and compensated liver disease 2 (with or without cirrhosis; Label, AASLD/IDSA 2016); B. Genotypes 1, 2, 3, or 4 and decompensated liver disease 2 with cirrhosis (Daklinza label, AASLD/IDSA 2016); AND VI. VII. Individual is 18 years of age or older; AND Individual is using with one of the following antiviral treatment regimens: A. In combination with peginterferon and ribavirin for one of the following: 1. Individuals with compensated 2 cirrhosis or without cirrhosis, Genotype 1; AND 2. Individual has had a prior trial (medication samples/coupons/discount to Mavyret Zepatier; 3. Individual is currently on and completing a course of therapy with the 4. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Mavyret Zepatier which is not also in Sovaldi; 5. Individual is concurrently using an agent that cannot be substituted with recommended for concomitant use with the preferred regimens; 6. Individual is treatment-naïve with compensated 2 cirrhosis or without cirrhosis, and Genotype 4; AND 7. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret Zepatier; 8. Individual is currently on and completing a course of therapy with the 9. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret Zepatier which is not also in Sovaldi; 10. Individual is concurrently using an agent that cannot be substituted with recommended for concomitant use with the preferred regimens; B. In combination with ribavirin for one of the following: 1. Individual is treatment-naïve with compensated 2 cirrhosis or without cirrhosis, Genotype 1, and is ineligible for an peginterferon-based regimen, as defined by the presence of one of the following: a. Intolerance to peginterferon (AASLD/IDSA 2016); PAGE 4 of 15 11/01/2017

5 b. Autoimmune disorders (AASLD/IDSA 2016), including autoimmune hepatitis; c. Child-Pugh score greater than 6 (Class B or C) 2 before or during peginterferon treatment; d. Known hypersensitivity to peginterferon agents; e. History of uncontrolled major depression, clinical features consistent with depression, or suicidal ideation (AASLD 2009, AASLD/IDSA 2016); f. Uncontrolled epilepsy (EASL 2016); g. Retinal disease (EASL 2016); h. Baseline neutrophil count below 1500/µL, baseline platelet count below 90,000/µL or baseline hemoglobin below 10 g/dl (AASLD/IDSA 2016); i. History of preexisting cardiac disease (AASLD/IDSA 2016); AND 2. Individual has had a prior trial (medication samples/coupons/discount to Mavyret Zepatier; 3. Individual is currently on and completing a course of therapy with the 4. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Mavyret Zepatier which is not also in Sovaldi; 5. Individual is concurrently using an agent that cannot be substituted with recommended for concomitant use with the preferred 6. Individual is treatment-naïve or dual (peginterferon and ribavirin) treatment-experienced, with compensated 2 cirrhosis or without cirrhosis, Genotype 2; AND 7. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; 8. Individual is currently on and completing a course of therapy with the 9. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi; 10. Individual is concurrently using an agent that cannot be substituted with 11. Individual is treatment-naïve or dual (peginterferon and ribavirin) treatment-experienced with compensated 2 cirrhosis or without cirrhosis, Genotype 3; AND 12. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; 13. Individual is currently on and completing a course of therapy with the PAGE 5 of 15 11/01/2017

6 14. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi; 15. Individual is concurrently using an agent that cannot be substituted with 16. Individual is post-liver allograft transplant with decompensated 2 cirrhosis and Genotype 3 (Forns et al. 2015); 17. Individuals with CHC and concurrent hepatocellular carcinoma meeting Milan criteria 3 (awaiting liver transplantation); 18. Individual is 12 to 17 years of age or older (or at least 35 kg), with compensated cirrhosis or without cirrhosis, and either Genotype 2 or 3; C. In combination with Olysio (simeprevir) in individuals without cirrhosis and Genotype 1 who meet the following: 1. Individual is treatment-naïve or dual (peginterferon and ribavirin) treatment-experienced; AND 2. Individual has had a prior trial (medication samples/coupons/discount to Mavyret Zepatier; 3. Individual is currently on and completing a course of therapy with the 4. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Mavyret Zepatier which is not also in Sovaldi or Olysio; 5. Individual is concurrently using an agent that cannot be substituted with recommended for concomitant use with the preferred regimens; D. In combination with Olysio (simeprevir) with (AASLD/IDSA 2016) or without ribavirin for one of the following: 1. Individuals with Genotype 1a or 1b with compensated 2 cirrhosis; AND 2. Individual is treatment-naïve or dual (peginterferon and ribavirin) treatment-experienced; AND 3. Individual has been screened and is negative for the NS3Q80K polymorphism associated with HCV Genotype 1a subtype (AASLD/IDSA 2016); AND 4. Individual has had a prior trial (medication samples/coupons/discount to Mavyret Zepatier; 5. Individual is currently on and completing a course of therapy with the 6. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Mavyret Zepatier which is not also in Sovaldi or Olysio; PAGE 6 of 15 11/01/2017

7 7. Individual is concurrently using an agent that cannot be substituted with recommended for concomitant use with the preferred 8. Individual is treatment-naïve, dual (peginterferon and ribavirin) treatmentexperienced, or triple [peginterferon, ribavirin, and a NS3 protease inhibitor (Olysio, Incivek or Victrelis)] treatment-experienced, post-liver allograft transplant recipient with compensated 2 cirrhosis or without cirrhosis, and Genotype 1 (AASLD/IDSA 2016); 9. Individual is triple [peginterferon, ribavirin, and Sovaldi (sofosbuvir)] treatment-experienced, post-liver allograft transplant recipient with compensated 2 cirrhosis or without cirrhosis, and Genotype 1 (AASLD/IDSA 2016); E. In combination with Daklinza (daclatasvir) for one of the following: 1. Individual is treatment-naïve, dual (peginterferon and ribavirin) treatment-experienced (AASLD/IDSA 2016), or triple [peginterferon, ribavirin and NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatment-experienced (AASLD/IDSA 2016) without cirrhosis, Genotype 1 (Daklinza label), and has had a prior trial (medication samples/coupons/discount cards are excluded from consideration as a trial) and inadequate response Mavyret Zepatier; 2. Individual is currently on and completing a course of therapy with the 3. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Mavyret Zepatier which is not also in Sovaldi or Daklinza; 4. Individual is concurrently using an agent that cannot be substituted with another agent or temporarily discontinued and is contraindicated or not recommended for concomitant use with the preferred 5. Individual is treatment-naïve or dual (peginterferon and ribavirin) treatment-experienced with compensated 2 cirrhosis or without cirrhosis, and Genotype 2 (AASLD/IDSA 2016); AND 6. Individual has had a prior trial (medication samples/coupons/discount cards are excluded from consideration as a trial) and inadequate response to Epclusa Mavyret; 7. Individual is currently on and completing a course of therapy with the 8. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi or Daklinza; 9. Individual is requesting for treatment in post-liver allograft transplant 10. Individual is concurrently using an agent that cannot be substituted with PAGE 7 of 15 11/01/2017

8 11. Individual is treatment-naïve, dual [peginterferon and ribavirin or sofosbuvir and ribavirin (Nelson et al. 2015)] treatment-experienced, or triple [peginterferon, ribavirin, and a NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatment-experienced (Nelson et al. 2015, Wyles et al. 2016) without cirrhosis and Genotype 3 (Daklinza label); AND 12. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; 13. Individual is currently on and completing a course of therapy with the 14. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi or Daklinza; 15. Individual is requesting for treatment in post-liver allograft transplant 16. Individual is concurrently using an agent that cannot be substituted with 17. Individual is treatment-naïve, with compensated 2 cirrhosis, and Genotype 3 (AASLD/IDSA 2016); AND 18. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; 19. Individual is currently on and completing a course of therapy with the 20. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi or Daklinza; 21. Individual is requesting for treatment in post-liver allograft transplant 22. Individual is concurrently using an agent that cannot be substituted with regimens; F. In combination with Daklinza (daclatasvir) with or without ribavirin for one of the following: 1. Individual is treatment-naïve, dual (peginterferon and ribavirin) treatmentexperienced (AASLD/IDSA 2016), or triple [peginterferon, ribavirin, and NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatmentexperienced (AASLD/IDSA 2016) with compensated 2 cirrhosis, Genotype 1, and has had a prior trial (medication samples/coupons/discount cards PAGE 8 of 15 11/01/2017

9 are excluded from consideration as a trial) and inadequate response to Mavyret Zepatier; 2. Individual is currently on and completing a course of therapy with the 3. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Mavyret Zepatier which is not also in Sovaldi or Daklinza; 4. Individual is concurrently using an agent that cannot be substituted with recommended for concomitant use with the preferred regimens; G. In combination with Daklinza (daclatasvir) and ribavirin for one of the following: 1. Individual is dual [sofosbuvir and ribavirin (Nelson et al. 2015, Wyles et al. 2015)] treatment-experienced with compensated 2 cirrhosis or without cirrhosis and Genotype 3 (AASLD/IDSA 2016); AND 2. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; 3. Individual is currently on and completing a course of therapy with the 4. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi or Daklinza; 5. Individual is requesting for treatment in post-liver allograft transplant 6. Individual is concurrently using an agent that cannot be substituted with 7. Individual is dual (peginterferon and ribavirin) treatment-experienced without cirrhosis, polymorphism present at the Y93H amino acid position, and Genotype 3 (AASLD/IDSA 2016); AND 8. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; 9. Individual is currently on and completing a course of therapy with the 10. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi or Daklinza; 11. Individual is requesting for treatment in post-liver allograft transplant 12. Individual is concurrently using an agent that cannot be substituted with PAGE 9 of 15 11/01/2017

10 13. Individual is treatment-naïve, dual (peginterferon and ribavirin) treatmentexperienced, or triple [peginterferon, ribavirin, and a NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatment-experienced, post-liver allograft transplant with compensated 2 cirrhosis or without cirrhosis, Genotypes 1 (Daklinza label) or 4 (AASLD/IDSA 2016); 14. Individual is treatment-naïve, dual (peginterferon and ribavirin) treatmentexperienced, or triple [peginterferon, ribavirin, and a NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatment-experienced, post-liver allograft transplant with compensated 2 cirrhosis or without cirrhosis, and Genotypes 2 (AASLD/IDSA 2016) or 3 (Daklinza label); 15. Individual is dual (sofosbuvir and ribavirin) treatment-experienced, (Poordad et al. 2016), post-liver allograft transplant with compensated 2 cirrhosis or without cirrhosis and Genotype 1(Daklinza Label), 2 (AASLD/IDSA 2016), 3 (Daklinza Label, or 4 (AASLD/IDSA 2016); 16. Individual is treatment-naïve, dual (peginterferon and ribavirin) treatmentexperienced, or triple [peginterferon, ribavirin, and a NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatment-experienced with decompensated 2 cirrhosis, Genotypes 1 (Daklinza label); 17. Individual is treatment-naïve, dual (peginterferon and ribavirin) treatmentexperienced, or triple [peginterferon, ribavirin, and a NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatment-experienced with decompensated 2 cirrhosis, and Genotypes 2 (AASLD/IDSA 2016) or 3 (Daklinza label); AND 18. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; 19. Individual is currently on and completing a course of therapy with the 20. Individual is requesting for treatment in post-liver allograft transplant 21. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi or Daklinza; 22. Individual is requesting for treatment in post-liver allograft transplant 23. Individual is concurrently using an agent that cannot be substituted with 24. Individual is treatment-naïve, dual [(peginterferon and ribavirin) treatmentexperienced, or triple [peginterferon, ribavirin, and a NS3 HCV protease inhibitor (Olysio, Incivek, or Victrelis)] treatment-experienced, with compensated 2 cirrhosis, and Genotype 3 (Daklinza label); AND 25. Individual has had a prior trial (medication samples/coupons/discount to Epclusa Mavyret; PAGE 10 of 15 11/01/2017

11 26. Individual is currently on and completing a course of therapy with the 27. Documented hypersensitivity, as manifested by a severe allergic reaction, to any ingredient in Epclusa Mavyret which is not also in Sovaldi or Daklinza; 28. Individual is requesting for treatment in post-liver allograft transplant 29. Individual is concurrently using an agent that cannot be substituted with regimens; H. In combination with Zepatier with or without ribavirin for one of the following: 1. Individual is dual (peginterferon and ribavirin) treatment-experienced, with compensated 2 cirrhosis and Genotype 3 (AASLD/IDSA 2017); 2. Individual dual [sofosbuvir and ribavirin (C-ISLE study)] treatmentexperienced with compensated 2 cirrhosis or without cirrhosis and Genotype 3 (AASLD/IDSA 2017). Sovaldi (sofosbuvir) may not be approved for the following: I. Individual has severe renal impairment (egfr less than 30 ml/min), end stage renal disease, or requires dialysis; II. Individual is using in combination with daclatasvir and a known NS5A polymorphism is present; III. Individual is requesting in concurrent therapy with contraindicated or not recommended agents, such as but not limited to the following: amiodarone, carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine, St John s Wort, tipranavir/ritonavir; IV. Individual is using in combination with a regimen containing a non-nucleoside NS5B polymerase inhibitor (such as dasabuvir) or another nucleotide NS5B polymerase inhibitor [such as ledipasvir/sofosbuvir or velpatasvir/sofosbuvir]; V. Individual is using in combination with a regimen containing a NS3/4A protease inhibitor other than simeprevir or elbasvir/grazoprevir [such as telaprevir, boceprevir, or paritaprevir,]; VI. Individual is using in combination with a regimen containing a NS5A inhibitor other than daclatasvir [(such as ombitasvir, ledipasvir/sofosbuvir, elbasvir/grazoprevir, or sofosbuvir/velpatasvir]; VII. Individual is requesting for re-treatment in combination with simeprevir and either failed to achieve a SVR (defined as a lower limit HCV RNA of 25 IU/mL) or relapsed after achieving a SVR during a prior successfully completed treatment regimen consisting of a NS3/4A protease inhibitor [such as simeprevir, paritaprevir, or elbasvir/grazoprevir]; VIII. Individual is requesting for re-treatment in combination with simeprevir and either failed to achieve a SVR (defined as a lower limit HCV RNA of 25 IU/mL) or relapsed after achieving a SVR during a prior successfully completed treatment regimen consisting of PAGE 11 of 15 11/01/2017

12 peginterferon, ribavirin, and telaprevir, boceprevir, simeprevir, or sofosbuvir, unless requested following a liver allograft transplant; IX. Individual is requesting for re-treatment in combination with simeprevir and either failed to achieve a SVR (defined as a lower limit HCV RNA of 25 IU/mL) or relapsed after achieving a SVR during a prior successfully completed treatment regimen consisting of a NS5A inhibitor [such as daclatasvir, ledipasvir/sofosbuvir, elbasvir/grazoprevir, ombitasvir, or sofosbuvir/velpatasvir]; X. Individual is requesting re-treatment in combination with simeprevir and either failed to achieve an SVR (defined as a lower limit HCV RNA of 25 IU/mL) or relapsed after achieving an SVR during a prior successfully completed treatment regimen consisting of a NS5B polymerase inhibitor [such as sofosbuvir, ledipasvir/sofosbuvir, dasabuvir, or sofosbuvir/velpatasvir]; XI. Individual is requesting for re-treatment in combination with daclatasvir and either failed to achieve a SVR (defined as a lower limit HCV RNA of 25 IU/mL) or relapsed after achieving a SVR during a prior successfully completed treatment regimen consisting of a NS5A inhibitor [such as daclatasvir, ledipasvir/sofosbuvir, elbasvir/grazoprevir, ombitasvir (AASLD/IDSA 2016) or sofosbuvir/velpatasvir]; XII. Individual is requesting for re-treatment in combination with daclatasvir and either failed to achieve a SVR (defined as a lower limit HCV RNA of 25 IU/mL) or relapsed after achieving a SVR during a prior successfully completed treatment regimen consisting of paritaprevir (AASLD/IDSA 2016) or elbasvir/grazoprevir; XIII. Individual is requesting the regimen for re-treatment in combination with daclatasvir and either failed to achieve a SVR (defined as a lower limit HCV RNA of 25 IU/mL) or relapsed after achieving a SVR during a prior successfully completed treatment regimen consisting of dasabuvir or sofosbuvir, ribavirin, and peginterferon; XIV. Individual is requesting in combination with ribavirin or peginterferon and ribavirin and has received previous treatment for hepatitis C virus (HCV) with one of the following: A. A peginterferon-based triple therapy regimen, which includes ribavirin and a NS3/4A inhibitor [telaprevir, boceprevir, or simeprevir], unless sofosbuvir and ribavirin are being requested following post-liver allograft transplant; B. A peginterferon-based triple therapy regimen, which includes ribavirin and sofosbuvir; C. A therapy regimen containing a NS5A inhibitor [such as ledipasvir/sofosbuvir, daclatasvir, ombitasvir, elbasvir/grazoprevir, or sofosbuvir/velpatasvir]; D. A therapy regimen containing a NS3/4A protease inhibitor [such as telaprevir, boceprevir, simeprevir, paritaprevir, or elbasvir/grazoprevir]; E. A therapy regimen containing a NS5B polymerase inhibitor [such as sofosbuvir, ledipasvir/sofosbuvir, dasabuvir, or sofosbuvir/velpatasvir]. Notes: 1. Per label and AASLD/IDSA 2016 treatment guidance, Sovaldi (sofosbuvir) may be used in individuals co-infected with HIV-1 either in combination with peginterferon and ribavirin (label), ribavirin (label), Olysio (simeprevir) (AASLD/IDSA 2016), or Daklinza (daclatasvir) (Daklinza label). The AASLD/IDSA cite case reports from Del Bello et al and preliminary results from Jacobson et al as clinical rationale to support co-infected use in Sovaldi + Olysio regimens. PAGE 12 of 15 11/01/2017

13 2. Compensated Liver Disease: According to the American Association for the Study of Liver Diseases (AASLD, 2009, 2016), the specific criteria for compensated liver disease include all of the following: a total bilirubin; serum albumin; prothrombin time/inr; presence of ascites; and presence of hepatic encephalopathy. However, these criteria do not establish a comprehensive definition of compensated liver disease. The AASLD guidance refers to compensated liver disease as Class A based on the Child Pugh-Turcotte (CPT) classification scoring system. Child Pugh Classification (AASLD/IDSA 2016) Parameters Points Assigned 1 point 2 points 3 points Total Bilirubin (µmol/l) < >50 Serum Albumin (g/l) > <28 Prothrombin time/inr < >2.30 Ascites None Mild Moderate to Severe Hepatic Encephalopathy None Grade I-II (or suppressed with medication Grade III-IV (or refractory) Child Pugh Score Interpretation (AASLD/IDSA 2009, 2016) Class A 5-6 points Well compensated liver disease Class B 7-9 points Significant functional compromise (moderate hepatic impairment) Class C points Uncompensated liver disease (severe hepatic impairment) Scoring Systems for Fibrosis Staging (AASLD 2009): Stage (F) IASL* Batts-Ludwig Metavir 0 No fibrosis No fibrosis No fibrosis 1 Mild fibrosis Fibrosis portal expansion Periportal fibrotic expansion 2 Moderate fibrosis Rare bridges or septae Periportal septae 1 (septum) 3 Severe fibrosis Numerous bridges or septae Porto-central septae 4 Cirrhosis Cirrhosis Cirrhosis *IASL = The International Association for the Study of Liver Stage (F) Ishak 0 No fibrosis 1 Fibrosis expansion of some portal areas with or without short fibrous septa 2 Fibrous expansion of most portal areas with or without short fibrous septa 3 Fibrous expansion of most portal areas with occasional portal to portal bridging 4 Fibrous expansion of most portal areas with marked bridging (portal to portal and portal to central) 5 Marked bridging (portal to portal and portal to central) with occasional nodules (incomplete cirrhosis) PAGE 13 of 15 11/01/2017

14 6 Cirrhosis 3. Milan criteria: A solitary tumor less than or equal to 5 cm or up to three (3) nodules less than or equal to 3 cm each with no extrahepatic manifestations or evidence of vascular invasion of tumor. 4. Hepatitis C virus (HCV) direct acting antiviral (DAA) agents have a black box warning for risk of hepatitis B virus (HBV) reactivation in individuals with HCV-HBV co-infection. Individuals should be tested for evidence of current or prior HBV infection prior to initiation of DAA therapy. HBV reactivation has been reported in HCV/HBV co-infected individuals currently taking or previously completed DAA therapy and not concomitantly receiving HBV antiviral therapy. Some cases of HBV reactivation have led to fulminant hepatitis, hepatic failure, and death. Individuals should be monitored for hepatitis flare or HBV reactivation during and following HCV DAA therapy. Individuals should be appropriately managed for HBV infection as indicated. Key References: American Association for the Study of Liver Diseases. Diagnosis, Management, and Treatment of Hepatitis C: An Update. AASLD Practice Guidelines. Hepatology. 2009; 49(4): Available from: Accessed on: February 9, American Association for the Study of Liver Diseases and the Infectious Disease Society of America, in collaboration with the International Antiviral Society-USA. Recommendations for testing, managing and treating hepatitis C. Available at Published on: January 29, Updated on: September 27, Accessed on: May 12, Bruix J and Sherman M. Management of Hepatocellular Carcinoma: An Update. An American Association for the Study of Liver Disease Practice Guideline. Hepatology. 2005; 42(5): Accessed on: February 9, Centers for Disease Control and Prevention. Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians. MMWR. 2013; 62(18): Available from: Accessed on: February 9, Charlton M, Gane E, Manns MP, et. al. Sofosbuvir and Ribavirin for Treatment of Compensated Recurrent Hepatitis C Virus Infection After Liver Transplantation. Available from: Gastroenterology. 2015; 148(1): Accessed on: February 9, Curry MP, O Leary JG, Bzowej N, ASTRAL-4 Investigators, et al. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015; 373: Available from: Accessed on: February 9, DailyMed. Package inserts. U.S. National Library of Medicine, National Institutes of Health website. Accessed on: March 1, Del Bello D, Cha A, Sorbera M, et al. Real-World Sustained Virologic Response Rates of Sofosbuvir-Containing Regimens in Patients Coinfected With Hepatitis C and HIV. Clin Infect Dis. 2016; 62(12): doi: /cid/ciw119. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C J Hepatol. 2017; 66(1): Available from: Accessed on: February 9, PAGE 14 of 15 11/01/2017

15 Feld JJ, Jacobson IM, Hezode C, ASTRAL-1 Investigators, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015; 373: Available from: Accessed on: February 9, Fontana RJ, Brown Jr RS, Moreno-Zamora A, et al. Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. Liver Transpl. 2016; 22(4): doi: /lt Forns X, Charlton M, Denning J, et al. Sofosbuvir Compassionate Use Program for Patients With Severe Recurrent Hepatitis C After Liver Transplantation. Hepatology. 2015; 61 (5): Available from: Accessed on: February 9, Foster GR, Afdhal N, Roberts SK, ASTRAL-2 and ASTRAL-3 Investigators, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015; 373: Available from: Accessed on: February 9, Foster GR, Irving WL, Cheung MC, et al. Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis J Hepatol. 2016; 64(6): doi: /j.jhep Herzer K, Papadopoulos-Kohn A, Walker A, et al. Daclatasvir, Simeprevir and Ribavirin as a Promising Interferon- Free Triple Regimen for HCV Recurrence after Liver Transplant. Digestion. 2015; 91(4): doi: / Incivek [Package insert]. Cambridge, MA. Vertex Pharmaceuticals Incorporated, Available from: Accessed on: February 9, Nelson DR, Cooper JN, Lalezari JP, et al. All-Oral 12-Week Treatment With Daclatasvir Plus Sofosbuvir in Patients With Hepatitis C Virus Genotype 3 Infection: ALLY-3 Phase III Study. Hepatology. 2015; 61(4): Available from: Accessed on: February 9, PL Detail-Document, Cytochrome P450 Drug Interactions. Pharmacist s Letter/Prescriber s Letter. May PL Detail-Document, OATP Drug Interactions. Pharmacist s Letter/Prescriber s Letter. March PL Detail-Document, P-glycoprotein Drug Interactions. Pharmacist s Letter/Prescriber s Letter. April Poordad F, Schiff ER, Vierling JM, et al. Daclatasvir With Sofosbuvir and Ribavirin for Hepatitis C Virus Infection With Advanced Cirrhosis or Post-Liver Transplantation Recurrence. Hepatology. 2016; 63(5): Available from: Accessed on: February 9, Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection. N Engl J Med. 2014; 370(3): Available from: Accessed on: February 9, U.S. Food & Drug Administration. Drugs@FDA: FDA Approved Drug Products (Package inserts). Available from: Accessed on: February 17, Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015; 373(8): Available from: Accessed on: February 9, Welzel TM, Petersen J, Ferenci P, et al. Safety and efficacy of daclatasvir plus sofosbuvir with or without ribavirin for the treatment of chronic HCV genotype 3 infection: Interim results of a multicenter European compassionate use program. 66 th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) [Abstract 37]. Hepatology. 2015; 62 (1): 225A. Available from: Accessed on: February 9, 2017 PAGE 15 of 15 11/01/2017