(glecaprevir/pibrentasvir) Override(s) Prior Authorization Quantity Limit Medication (glecaprevir/pibrentasvir) Approval Duration Based on Genotype, Treatment Status, or Cirrhosis Status. Quantity Limit 3 tablets per day APPROVAL DURATION Genotype and Status (HCV mono-infected) Genotypes 1, 2, 3, 4, 5, or 6 (treatment-naïve*, without cirrhosis) Genotypes 1, 2, 3, 4, 5, or 6 (treatment-naïve*, with compensated cirrhosis) Genotype 1 (treatment-experienced ± with an NS5A inhibitor 2 and without prior treatment with an NS3/4A protease inhibitor 3, with compensated cirrhosis or without cirrhosis) Genotype 1 (treatment-experienced ± with an NS3 /4A protease inhibitor 3 and without prior treatment with an NS5A inhibitor 2, with compensated cirrhosis or without cirrhosis) Genotype 3 (dual* treatment-experienced or triple treatment-experienced, with compensated cirrhosis or without cirrhosis) Genotypes 1, 2, 4, 5, or 6 (dual* treatmentexperienced, or triple treatment-experienced, without cirrhosis) Genotypes 1, 2, 4, 5, and 6 (dual* treatmentexperienced, or triple treatment-experienced, with compensated cirrhosis) Associated Treatment Regimens Total Approval Duration for (glecaprevir/pibrentasvir) 8 weeks 12 weeks 16 weeks 12 weeks 16 weeks 8 weeks 12 weeks 2 = NS5A inhibitor regimens included ledipasvir and sofosbuvir or daclatasvir with peginterferon and ribavirin. 3 = NS3/4A protease inhibitor regimens included simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with peginterferon and ribavirin. *The ENDURANCE-1, -2,-4 (AASLD October 2016 abstracts); EXPEDITION-IV (Gane AASLD abstract 2016); SURVEYOR-I (Kwo 2017; EASL April 2016); and SURVEYOR-II parts 2-4 (Kwo 2017; EASL April 2016) clinical trials define dual treatment-experienced as a prior trial of interferon/peginterferon and ribavirin and/or sofosbuvir. PAGE 1 of 7 09/01/2017 WEB-PEC-0681-17
± The MAGELLAN-1 part 1 (Poordad et al. 2016, 2017) clinical trial defines DAA treatment-experienced as a prior trial of NS3/4A protease inhibitors; (simeprevir, asunaprevir, boceprevir, telaprevir, paritaprevir) OR NS5A inhibitors (ledipasvir, daclatasvir, ombitasvir). The ENDURANCE-1, -2,-4; EXPEDITION-IV; and SURVEYOR-I, -II clinical trials define triple treatmentexperienced as a prior trial of peginterferon, ribavirin, and sofosbuvir. APPROVAL CRITERIA Requests for (glecaprevir/pibrentasvir) may be approved if the following criteria are met: I. Individual is 18 years of age or older; AND II. A copy of the baseline quantitative hepatitis C virus (HCV) RNA test result is provided to document baseline level of viremia; AND III. One of the following: A. Documentation is provided for an FDA approved, compendia supported, or Medicaid covered diagnosis of chronic hepatitis C (CHC) infection, which includes 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 2017, CDC 2013); OR 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, co infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV), coexistent liver diseases (such as nonalcoholic steatohepatitis), chronic HCV infection associated extrahepatic manifestations (such as membranoproliferative glomerulonephritis, glomerular disease, cryoglobulinemia syndrome)] (AASLD/IDSA 2017); AND C. Documentation is provided for an FDA approved, compendia supported, or Medicaid covered diagnosis of CHC infection, which includes a reactive HCV antibody (CDC 2013), and a subsequent positive HCV RNA result (CDC 2013); AND IV. 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 2017); AND V. Individual has compensated liver disease 1 (with or without cirrhosis); AND VI. Individual is using in the following antiviral treatment regimen: A. As monotherapy for one of the following: 1. Individual is treatment-naïve, with compensated 1 cirrhosis or without cirrhosis, and Genotypes 1, 2, 3, 4, 5, or 6; OR 2. Individual is treatment-experienced with a prior HCV NS5A inhibitor regimen (ledipasvir and sofosbuvir or daclatasvir with peginterferon with ribavirin) without prior HCV treatment with an NS3/4A protease inhibitor (simeprevir and sofosbuvir or simeprevir, boceprevir, telaprevir with PAGE 2 of 7 09/01/2017
VIII. peginterferon and ribavirin) with compensated 1 cirrhosis or without cirrhosis, and Genotype 1; OR 3. Individual is treatment-experienced with a prior HCV NS3/4A protease inhibitor regimen (simeprevir and sofosbuvir or simeprevir, boceprevir, telaprevir with peginterferon and ribavirin) without prior HCV treatment with an NS5A inhibitor (ledipasvir and sofosbuvir or daclatasvir with peginterferon with ribavirin), with compensated cirrhosis 1 or without cirrhosis, and Genotype 1; OR 4. Individual is dual or triple treatment-experienced (peginterferon/interferon and ribavirin, or peginterferon and ribavirin and sofosbuvir) but without prior treatment-experience with an HCV NS3/4A protease inhibitor regimen (simeprevir and sofosbuvir or simeprevir, boceprevir, telaprevir with peginterferon and ribavirin) or NS5A inhibitor (ledipasvir and sofosbuvir or daclatasvir with peginterferon with ribavirin), with compensated cirrhosis 1 or without cirrhosis, and Genotypes 1, 2, 3, 4, 5, or 6. AND Prescriber meets the following experience and training (http://www.health.ny.gov/health_care/medicaid/program/dur/hepa_c_virus.htm): A. Prescriber is a hepatologist, gastroenterologist, infectious disease specialist, transplant physician or health care practitioner experienced and trained in the treatment of Hepatitis C viral (HCV) or a healthcare practitioner under the direct supervision of a listed specialist; AND B. Prescriber has clinical experience defined as: 1. Management and treatment of at least 10 patients with HCV infection in the last 12 months and at least 10 HCV- related CME credits in the last 12 months; OR 2. Management and treatment of HCV infection in partnership (defined as consultation, preceptorship, or via telemedicine) with an experienced HCV provider who meets the above criteria (glecaprevir/pibrentasvir) may not be approved for the following: I. Individual has moderate to severe hepatic impairment (Child-Pugh Class B-C); OR II. Individual is requesting in concurrent therapy with contraindicated or not recommended agents, such as but not limited to atazanavir and rifampin; OR III. Individual is using in combination with a regimen containing a non-nucleoside NS5B polymerase inhibitor (such as dasabuvir) or nucleotide NS5B polymerase inhibitor [such as sofosbuvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevir]; OR IV. Individual is using in combination with a regimen containing another NS5A inhibitor [such as daclatasvir, ledipasvir/sofosbuvir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, ombitasvir, or sofosbuvir/velpatasvir/voxilaprevir]; OR PAGE 3 of 7 09/01/2017
V. Individual is using in combination with a regimen containing another NS3/4A protease inhibitor [such as simeprevir, elbasvir/grazoprevir, paritaprevir, or sofosbuvir/velpatasvir/voxilaprevir]; OR VI. Individual is requesting the regimen for re-treatment 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 sofosbuvir/velpatasvir, elbasvir/grazoprevir, ombitasvir/paritaprevir/ritonavir and dasabuvir, ombitasvir/paritaprevir/ritonavir, sofosbuvir/velpatasvir/voxilaprevir. Notes: 1. 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) <34 34-50 >50 Serum Albumin (g/l) >35 28-35 <28 Prothrombin time/inr <1.7 1.71-2.30 >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 10-15 points Uncompensated liver disease (severe hepatic impairment) 2. Metavir Scoring System for Fibrosis Staging (AASLD 2009): Stage (F) 0 No Fibrosis 1 Periportal fibrotic expansion 2 Periportal septae 1 (septum) 3 Porto central septae 4 Cirrhosis PAGE 4 of 7 09/01/2017
3. 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):1335-74. Available from: http://onlinelibrary.wiley.com/doi/10.1002/hep.22759/pdf. Accessed on: February 9, 2017. 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 http://www.hcvguidelines.org/. Published on: January 29, 2014. Updated on: September 27, 2016. Accessed on: May 12, 2017. Bourliere M, Gordon SC, Flamm SL et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. New Engl J Med. 2017; 22:2134-46. 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):1208-1236. http://onlinelibrary.wiley.com/doi/10.1002/hep.20933/epdf. Accessed on: February 9, 2017. Centers for Disease Control and Prevention. Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians. MMWR. 2013; 62(18):362-365. Available from: https://www.cdc.gov/mmwr/pdf/wk/mm6218.pdf. Accessed on: February 9, 2017. 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: http://www.gastrojournal.org/article/s0016-5085(14)01194-9/pdf/. Gastroenterology. 2015; 148(1):108 117. Accessed on: February 9, 2017. 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; 373:2618-2628. Available from: http://www.nejm.org/doi/pdf/10.1056/nejmoa1512614. Accessed on: February 9, 2017. DailyMed. Package inserts. U.S. National Library of Medicine, National Institutes of Health website. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Accessed on: March 1, 2017. 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):1497-1504. doi: 10.1093/cid/ciw119. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol. 2017; 66(1):153-194. Available from: http://www.journal-of-hepatology.eu/article/s0168-8278(16)30489-5/pdf. Accessed on: February 9, 2017. 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; 373:2599-607. Available from: http://www.nejm.org/doi/pdf/10.1056/nejmoa1512610. Accessed on: February 9, 2017. PAGE 5 of 7 09/01/2017
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): 446-458. doi: 10.1002/lt.24416. 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):1485-1494. Available from: http://onlinelibrary.wiley.com/doi/10.1002/hep.27681/pdf. Accessed on: February 9, 2017. 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; 373:2608-2617. Available from: http://www.nejm.org/doi/pdf/10.1056/nejmoa1512612. Accessed on: February 9, 2017. 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):1224-31. doi: 10.1016/j.jhep.2016.01.029. 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):326-333. doi: 10.1159/000382075. Incivek [Package insert]. Cambridge, MA. Vertex Pharmaceuticals Incorporated, 2013. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201917s012lbl.pdf. Accessed on: February 9, 2017. Kwo P, Poordad F, Astryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatology. 2017; 67: 263-71. [Package insert]. North Chicago, IL. AbbVie Inc. 2017. Available from: http://www.rxabbvie.com/pdf/mavyret_pi.pdf?_ga=2.18286202.2140952231.1501621355-778444936.1499790328. Accessed on August 3, 2017. 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): 1127 1135. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4409820/pdf/hep0061-1127.pdf. Accessed on: February 9, 2017. PL Detail-Document, Cytochrome P450 Drug Interactions. Pharmacist s Letter/Prescriber s Letter. May 2016. PL Detail-Document, OATP Drug Interactions. Pharmacist s Letter/Prescriber s Letter. March 2014. PL Detail-Document, P-glycoprotein Drug Interactions. Pharmacist s Letter/Prescriber s Letter. April 2016. 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):1493-1505. Available from: http://onlinelibrary.wiley.com/doi/10.1002/hep.28446/pdf. Accessed on: February 9, 2017. 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):211-21. Available from: http://www.nejm.org/doi/pdf/10.1056/nejmoa1306218. Accessed on: February 9, 2017. U.S. Food & Drug Administration. Drugs@FDA: FDA Approved Drug Products (Package inserts). Available from: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed on: February 17, 2017. Vosevi [Package insert]. Foster City, CA. Gilead Science, Incorporated, 2017. Available from: http://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/vosevi/vosevi_pi.pdf?la=en. Accessed on: July 20, 2017. 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):714-25. Available from: http://www.nejm.org/doi/pdf/10.1056/nejmoa1503153. Accessed on: February 9, 2017. PAGE 6 of 7 09/01/2017
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. 66th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) [Abstract 37]. Hepatology. 2015; 62 (1): 225A. Available from: http://onlinelibrary.wiley.com/doi/10.1002/hep.28172/epdf. Accessed on: February 9, 2017. PAGE 7 of 7 09/01/2017