Hepatitis C Second Generation Antivirals (Harvoni, Technivie TM, Viekira Pak ) Prior Authorization - Through Preferred Agent(s) Program Summary

Transcription

1 Hepatitis C Second Generation Antivirals (Harvoni, Technivie TM, Viekira Pak ) Prior Authorization - Through Preferred Agent(s) Program Summary This program applies to Health Insurance Marketplace, FlexRx Closed, FlexRx Open, GenRx Closed, and GenRx Open formularies. This program does not apply to BCBS MN Medicaid population. FlexRx Open, GenRx Open, and Health Insurance Marketplace formularies target Harvoni, Technavie, and Viekira. FlexRx Closed and GenRx Closed formularies target Harvoni. Technavie and Viekira are non-formulary agents. Harvoni is the preferred product. This is a FlexRx standard and GenRx standard prior authorization program. Medication Indications Dose and Interval Harvoni (ledipasvir-sofosbuvir) Treatment of chronic hepatitis C, genotype 1 infection Treatment, in combination with ribavirin, of chronic hepatitis C genotype 4 without cirrhosis Limitation: Technivie is not Technivie recommended for use in patients (ombitasvir/paritaprevir/ritonavir) with moderate hepatic impairment (Child-Pugh B) and is contraindicated for patients with severe hepatic impairement (Child-Pugh C) Viekira Pak (ombitasvir/paritaprevir/ritonavir and dasabuvir) With or without ribavirin in HCV genotype 1 patients including those with compensated cirhhosis. Limitation: Not recommended for use in patients with decompensated liver disease 1 tablet orally once daily containing 90 mg of ledipasvir and 400 mg of sofosbuvir for up to 24 weeks Two ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg tablets once daily (in the morning) for 12 weeks Two ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg tablets once daily (in the morning) and one dasabuvir 250 mg tablet twice daily (morning and evening) for 12 to 24 weeks. Ledipasvir/sofosbuvir 1,2,3,8 Safety and efficacy of this combination ± ribavirin was evaluated in 3 open label studies which included treatment naïve, previous failures, cirrhotic and non-cirrhotic genotype 1 patients. The ION studies (1, 2, and 3) all had a primary efficacy endpoint of a sustained virologic response (SVR) at 12 weeks after the end of therapy. ION-1 was conducted in previously untreated patients including those with compensated cirrhosis. Up to 20% of patients could be cirrhotic (defined as a Metavir stage of F4). ION-2 was conducted in patients who had not had an SVR after treatment with peginterferon + ribavirin with our without a protease inhibitor. In this study 52% of patients had received a prior treatment regimen with a protease inhibitor. ION-3 was evaluated in treatment naïve patients without cirrhosis. All three of these trials showed efficacy in these patient populations. SVR rates in these trials ranged from 93% to 100%. Guideline recommendations for patients that have failed a sofosbuvir containing regimen recommend that patients with advanced fibrosis receive ledipasvir/sofosbuvir plus ribavirin and patients without advanced fibrosis either enter a clinical trial or defer further therapy until such a time more evidence is available. 8 MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 1 of 10

2 The America Association for the Study of Liver Disease and Infection Disease Society of America (AASLD/IDSA) guidelines recommend ledipasvir/sofosbuvir for treatment of hepatitis C genotype 4, 5, 6. 7,8 The recommended duration of treatment is 12 weeks for treatment naïve patients and those with prior failure of peg-interferon plus ribavirin. Ombitasvir/paritaprevir/ritonavir and dasabuvir 13,14,15 Safety and efficacy of this combination was evaluated in 4 pivotal trials including treatment naïve, previous failures, cirrhotics and non-cirrhotic genotype 1 patients. The studies (Sapphire I, Turquoise II, Pearl III and Pearl IV) all had a primary efficacy endpoint of a sustained virologic response (SVR) at 12 weeks after the end of therapy. Sapphire I was conducted in treatment naïve patients without cirrhosis. Turquoise-2 was conducted in treatment naïve and previously treated patients and included cirrhotic patients. Pearl III evaluated treatment naïve genotype 1b patients and Pearl IV evaluated treatment naïve genotype 1a patients. SVR rates in these trials ranged from 90% to 99%. Treatment guidelines recommend that patients that have failed a previous protease inhibitor containing regimen receive ledipasvir/sofosbuvir. Ombitasvir/paritaprevir/ritonavir + dasabuvir is not a recommended regimen in previous protease inhibitor failures due to risk of resistance. 8 Ombitasvir/paritaprevir/ritonavir 19,20 Efficacy and safety of this combination, when used with or without ribavirin, was evaluated in a single clinical trial (PEARL-I). The study enrolled 135 subjects with chronic hepatitis C (HCV) infection genotype 4 without cirrhosis. The subjects were either treatment naïve or had history of virologic failure following treatment with pegylated interferon and ribavirin. The primary end point of the study was sustained virologic response at 12 weeks (SVR 12) following completion of therapy. SVR 12 was 100% for treatment naïve and treatment experienced subjects whose regimen included ribavirin and 91% for treatment naïve patients whose regimen did not include ribavirin. Safety and efficacy of this combination regimen has not been studied in patients previously treated with a direct acting antiviral. The most common adverse events reported in the trial were asthenia, fatigue, nausea, insomnia, pruritis, and skin reaction. These adverse events were graded as mild in severity. Hepatitis C Hepatitis C is an infection of the liver caused by the Hepatitis C virus (HCV); a blood borne virus. An acute HCV infection is defined as presenting within 6 months following exposure to the virus. 18 The infection is defined as chronic if the virus is present beyond six months following exposure. Persons at high risk for contracting HCV infection include intravenous drug user, recipients of donated blood, blood products, and organs (now rare in the United States due to stringent blood screening), babies born to HCV infected mothers, and persons with HIV infection. HCV infection is asymptomatic in the early stages of the disease. However, with disease progression, patients may develop mild to severe chronic liver disease including cirrhosis and liver cancer. Disease progression should be monitored by evaluating liver fibrosis. The diagram below correlates METAVIR scores with fibrosis stages. METAVIR scores which describe liver damage are determined by liver biopsy. Liver biopsy is an invasive procedure and the current standard in viral hepatitis for staging the degree of injury and not for achieving a diagnosis. 11 Biopsy scoring systems for liver fibrosis including Metavir, Scheuer, Ishak and histological activity index give a number to a pattern of fibrosis. Fibroscan measures liver stiffness in kpa which correlates with increased fibrosis. Diagnosis of significant fibrosis (F>1) and cirrhosis measurements were 7.65 kpa and kpa, respectively. 11 Study data shows that Ishak fibrosis stages of 3 represent clinically progressive liver disease. Data from the HALT-C study showed that patients with Ishak fibrosis stage 2 had no clinical outcomes until nearly 5 years after randomization and closer to 6 years after the baseline biopsy. 12 MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 2 of 10

3 10 AASLD/IDSA guidelines on when and in whom to treat: 4 The goal of therapy is to reduce all-cause mortality and liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma, by the achievement of virologic cure as evidenced by an SVR. Evaluation of the degree of hepatic fibrosis using noninvasive testing or liver biopsy is recommended prior to starting treatment. Treatment is assigned the highest priority for those patients with advanced fibrosis (Metavir F3), those with compensated cirrhosis (Metavir F4), liver transplant recipients, and patients with severe extrahepatic hepatitis C. Based on available resources, treatment should be prioritized as necessary so that patients at high risk for liver-related complications and severe extrahepatic hepatitis C complications are given high priority. Highest Priority for Treatment Owing to Highest Risk for Severe Complications o Advanced fibrosis (Metavir F3) or compensated cirrhosis (Metavir F4) o Organ Transplant o Type 2 or 3 essential mixed cryoglobulinemia with end-organ manifestations (eg. Vasculitis) o Proteinuria, nephritic syndrome, or membranoproliferative glomerulonephritis High Priority For Treatment Owing to High Risk for Complications o Fibrosis (Metavir F2) o HIV-1 Co-infection o HBV Co-infection o Other coexistent liver disease (e.g., NASH) o Debilitating fatigue o Type 2 diabetes mellitus (insulin resistant) o Porphyria cutanea tarda AASLD guidelines on management of acute hepatitis C infection. 18 Patients diagnosed with acute HCV infection should be monitored regularly to determine if the infection has cleared or progressed into chronic HCV infection. If a decision is made to treat, AASLD guidelines recommend the same regimens recommended for treatment of chronic HCV. Treatment with antiviral therapy is not recommended for pre-exposure or post-exposure prophylaxis or for those in whom the acute infection clears spontaneously. MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 3 of 10

4 References (not all references are used in this version): 1. Afdal N, Zeuzem S, Kwo P et al. Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection. New England Journal of Medicine 2014;370: Afdal N, Reddy KR, Nelson DR et al. Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection. New England Journal of Medicine 2014;370: Kowdley K, Gordon S, Reddy KR et al. Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis. New England Journal of Medicine 2014;370: AASLD Treatment Guidelines. When and In Whom to Initiate HCV Therapy. Available at: Accessed 10/2/ (paritaprevir/ritonavir/ombitasvir and dasabuvir) prescribing information. Abbvie. Available at: Accessed 10/2/ Harvoni (ledipasvir-sofosbuvir) prescribing information. Available at: Accessed 10/2/ AASLD Treatment Guidelines, Treatment Naïve or who have experienced relapse after prior PEG/RBV therapy. Available at: Accessed 8/13/ AASLD Treatment Guidelines, Retreatment of person in whom prior therapy has failed. Available at: Accessed 12/22/ AASLD Treatment Guidelines, Unique Populations. Available at: Accessed 10/2/ Photo - epgonline.org. Hepatology. Accessed: February Scott DR, Levy MT. Liver transient elastography (Fibroscan ): a place in the management algorithms of chronic viral hepatitis. Antiviral Therapy 2010;15:1-11 (doi: /IMP1474). 12. Everhart JE, Wright EC, Goodman ZD et al. Prognostic Value of Ishak Fribrosis Stage: Findings from the HALT-C Trial. Hepatology 2010 February:51(2): doi: /hep 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: 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;370: 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: Viekira Pak prescribing information. Abbvie, Inc. North Chicago, IL. March Osinusi A, Marti M, Kohli A et al. Sofosbuvir/ledipasvir in retreatment of HCV genotype-1 patients who previously failed sofosbuvir/ribavirin therapy. [Abstract 011.] 49th Annual Meeting of the European Association for the Study of the Liver (EASL). April 9-13, 2014a; London, United Kingdom 18. AASLD Treatment Guidelines, Management of Acute Hepatitis C Infection. Available at: Accessed 10/2/ Technivie (ombitasvir/paritaprevir/ritonavir) prescribing information. Available at Accessed 10/2/ Hezode C, Asselah T, Reddy K, et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naïve and treatment experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I):a randomized, open-label trial. Lancet 2015;385: MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 4 of 10

5 Hepatitis C Second Generation Antivirals (Harvoni [ledipasvir/sofosbuvir] and Viekira Pak [ombitasvir/paritaprevir/ritonavir + dasabuvir]) Prior Authorization Through Preferred Agent(s) OBJECTIVE The intent of the Hepatitis C second generation antiviral Prior Authorization (PA) program is to appropriately select patients for therapy according to the Food and Drug Administration (FDA) approved product labeling and/or clinical guidelines and/or clinical studies. The PA process will evaluate the use of these agents when there is supporting clinical evidence for their use. Patients requesting Harvoni that are treatment naïve, non-cirrhotic, are not HIV coinfected, and have an initial viral load < 6 M IU/mL will be approved for 8 weeks assuming all other criteria are met. The preferred agent may be approved for use once criteria has been met; a non-preferred agent may be approved if the patient is currently treated with the non-preferred agent or the prescriber has documented failure of, intolerance to, FDA labeled contraindication to, or hypersensitivity to the preferred agent(s). For the use of Sovaldi (sofosbuvir) see Sovaldi specific criteria. For the use of Olysio in combination with peginterferon and ribavirin, see Hepatitis C First Generation criteria. See the Sovaldi (sofosbuvir) criteria for Daklinza in combination with sofosbuvir and for patients with hepatocellular carcinoma. TARGET DRUGS Preferred Agent(s): Harvoni (ledipasvir/sofosbuvir) Non-preferred Agent(s): Viekira Pak (ombitasvir/paritaprevir/ritonavir + dasabuvir) PRIOR AUTHORIZATION CRITERIA FOR APPROVAL Initial Evaluation Harvoni (ledipasvir/sofosbuvir) will be approved when the following criteria are met: 1. ONE of the following is met: A. There is documentation that the patient is currently using the requested agent OR B. The patient is new to therapy and ALL of the below: a. The patient has a diagnosis of chronic hepatitis C confirmed by serological markers b. The prescriber has provided a baseline HCV RNA level c. The agent is being prescribed by a specialist (i.e. gastroenterologist, hepatologist, or infectious disease) or in consultation with a specialist d. These agents will not be used in combination with other protease inhibitors used to treat chronic hepatitis C (i.e. boceprevir, simeprevir, or telaprevir) e. The patient does not have any FDA labeled contraindications to therapy with the requested agent Agent(s) Contraindication(s) Harvoni (ledipasvir/sofosbuvir) None Viekira Pak (ombitasvir/paritaprevir/ritonavir + dasabuvir) Known hypersensitivity to ritonavir, severe hepatic impairment, co-administration with drugs that are highly dependent on CYP3A for clearance, strong inducers of CYP3A and CYP2C8, and strong inhibitors of CYP2C8 When co-administered with RBV: pregnancy, MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 5 of 10

6 males whose female partners are pregnant, patients with hemoglobinopathies (e.g. thalassemia major or sickle-cell anemia) and in combination with didanosine f. The patient does not have hepatocellular carcinoma (see Sovaldi criteria for approval) g. The patient is not co-infected with chronic hepatitis B h. ONE of the following: 1. The patient has a METAVIR score of 2 OR 2. The patient has a Ishak score 3 OR 3. The patient has a Fibroscan score of 7.65 kpa OR 4. The patient has radiological imaging consistent with fibrosis and/or cirrhosis (e.g. portal hypertension, esophageal varices) OR 5. The patient has type 2 or 3 mixed cryoglobulinemia with end-organ manifestations (e.g. vasculitis) OR 6. The patient has proteinuria, nephrotic syndrome, or membranoproliferative glomerulonephritis OR 7. The patient is currently awaiting liver transplant OR 8. The patient is post-liver transplant OR 9. The patient is co-infected with HIV-1 i. If the request is for Viekira (ombitasvir/paritaprevir/ritonavir + dasabuvir) ALL of the following: 1. The patient has chronic hepatitis C genotype 1 2. The agent will be used in a combination antiviral treatment regimen supported by FDA approved labeling (see Table 2 below) 3. The patient has not been previously treated for chronic hepatitis C with a regimen containing daclatasvir, dasabuvir, ombitasvir, paritaprevir, ritonavir, sofosbuvir, simeprevir, telaprevir, or boceprevir 4. The patient s subtype has been identified and provided 5. The patient does not have decompensated liver disease j. If the request is for Harvoni, ONE of the following: 1. ALL of the following: a. The patient has chronic hepatitis C genotype 1 b. The patient has not been previously treated with Daklinza (daclatasvir), Viekira (ombitasvir/paritaprevir/ritonavir + dasabuvir), Harvoni (ledipasvir/sofosbuvir), or Technivie (ombitasvir/paritaprevir/ritonavir) c. ONE of the following: i. The patient has NOT failed a previous sofosbuvir containing regimen OR ii. BOTH of the following: 1. The patient has failed a previous sofosbuvir containing regimen, not including Harvoni (ledipasvir/sofosbuvir) 2. The patient has advanced fibrosis (Metavir F3 or F4) OR 2. BOTH of the following: a. The patient has chronic hepatitis C genotype 4, 5, or 6 MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 6 of 10

7 b. The patient has not been previously treated with Daklinza (daclatasvir), Harvoni (ledipasvir/sofosbuvir), Sovaldi (sofosbuvir), Technivie (ombitasvir/paritaprevir/ritonavir), Viekira (ombitasvir/paritaprevir/ritonavir + dasabuvir), or a protease inhibitor (e.g. Incivek, Victrelis, Simeprevir) 2. The dose is within the FDA labeled dose (90 mg of ledipasvir/400 mg of sofosbuvir or 25 mg ombitasvir/150 mg paritaprevir/100 mg ritonavir plus 250 mg twice daily of dasabuvir) Length of Approval: Up to 24 weeks as determined in Tables 1 and 2 below Table 1 Harvoni Treatment Duration Recommendations based on FDA labeling and/or AASLD/IDSA treatment guidelines Genotype Patient Population Treatment Duration 1 Treatment naïve without cirrhosis or without HIV infection and initial viral load < 6 M IU/mL Treatment naïve with or without cirrhosis Treatment experienced** without cirrhosis Treatment experienced** with cirrhosis 8 weeks* 12 weeks* 12 weeks 24 weeks 4 Treatment naïve or treatment experienced 12 weeks 5 Treatment naïve or treatment experienced 12 weeks 6 Treatment naïve or treatment experienced 12 weeks *8 weeks may be considered in treatment naïve patients without cirrhosis or without HIV infection who have pretreatment HCV RNA < 6 million IU/mL. For this patient population BCBS MN is requiring 8 weeks of therapy. **Treatment-experienced patients who have failed therapy with either peginterferon + ribavirin or a HCV protease inhibitor + peginterferon + ribavirin. Table 2 Viekira Treatment Duration Recommendations based on FDA labeling Patient Population Treatment Duration Genotype 1a, no cirrhosis Viekira + RBV 12 weeks Genotype 1a, cirrhosis Viekira + RBV 24 weeks** Genotype 1b, no cirrhosis Viekira 12 weeks Genotype 1b, cirrhosis Viekira + RBV 12 weeks **Viekira with RBV for 12 weeks may be considered for some patients based on prior treatment history. The SVR12 rate difference between 24 and 12 weeks of treatment was +6% with differences varying by pretreatment history. ^HCV/HIV-1 coinfection, follow recommendations in table 2 above ^Liver transplant patients with normal hepatic function and mild fibrosis (Metavir 2), recommended duration with RBV is 24 weeks Non-Preferred Agent(s) (Viekira Pak [ombitasvir/paritaprevir/ritonavir + dasabuvir]) will be approved when the ONE of the following are met in addition to the criteria noted above for the preferred agent: 1. The patient is currently being treated with the non-preferred agent OR 2. The patient has an FDA labeled contraindication, documented intolerance, or hypersensitivity to the preferred agent(s) OR MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 7 of 10

8 3. The prescriber has submitted documentation in support of the use of the non-preferred agent(s), for the intended diagnosis which has been reviewed and approved by the Clinical Review pharmacist Length of approval: Up to 24 weeks based on regimen MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 8 of 10

9 Hepatitis C Second Generation Antivirals (Technivie TM [ombitasvir/ paritaprevir/ritonavir]) Prior Authorization Through Preferred Agent(s) Objective The intent of the Hepatitis C second generation antiviral Prior Authorization (PA) program is to appropriately select patients for therapy according to the Food and Drug Administration (FDA) approved product labeling and/or clinical guidelines and/or clinical studies. The PA process will evaluate the use of these agents when there is supporting clinical evidence for their use. This program requires patients requesting Technivie have not been previously treated for chronic hepatitis C with a direct acting antiviral (DAA). If the client has preferred agent(s), a preferred agent may be approved for use once criteria has been met; a non-preferred agent may be approved if the patient is currently treated with the nonpreferred agent or the prescriber has documented failure of, intolerance to, FDA labeled contraindication to, or hypersensitivity to the preferred agent(s). For the use of Sovaldi (sofosbuvir) see Sovaldi specific criteria. For the use of Olysio in combination with peginterferon and ribavirin, see Hepatitis C First Generation criteria. For hepatocellular carcinoma patients see Sovaldi (sofosbuvir). TARGET DRUG(S) Non-preferred agent(s) Technivie TM (ombitasvir/paritaprevir/ritonavir) PRIOR AUTHORIZATION CRITERIA FOR APPROVAL Initial Evaluation Technivie (ombitasvir/paritaprevir/ritonavir) will be approved when ALL of the following criteria are met: 1. ONE of the following: a. There is documentation that the patient is currently using the requested agent OR b. ALL of the following: i. The patient has a diagnosis of chronic hepatitis C, genotype 4 confirmed by serological markers ii. The patient does not have any of the following: 1. Cirrhosis OR 2. Decompensated liver disease OR 3. Moderate or severe hepatic impairment (Child-Pugh B or C) iii. The requested agent is being prescribed by a specialist (i.e. gastroenterologist, hepatologist, or infectious disease) or in consultation with a specialist iv. The requested agent will be used in a combination antiviral treatment regimen supported by FDA approved labeling (see Table 1 below) v. The patient has not been previously treated with the requested agent or with a regimen containing a direct acting antiviral (DAA) indicated for chronic hepatitis C (e.g. Daklinza, Harvoni, Incivek, Olysio, Sovaldi, Victrelis, or Viekira) vi. The patient will not use the requested agent in combination, with a regimen containing a direct acting antiviral (DAA) indicated for chronic hepatitis C (e.g. Daklinza, Harvoni, Incivek, Olysio, Sovaldi, Victrelis, or Viekira) vii. The patient does not have Hepatocellular Carcinoma (HCC) MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 9 of 10

10 viii. The patient is not co-infected with Hepatitis B virus (HBV) ix. ONE of the following: 1. The patient has a METAVIR score of 2 or 3 OR 2. The patient has a Ishak score of 3 to 5 OR 3. The patient has a Fibroscan score of 7.65 kpa to kpa OR 4. The patient is post-liver transplant OR 5. The patient is co-infected with HIV-1 x. The patient does not have any FDA labeled contraindication(s) to therapy with the requested agent 2. The dose is within the FDA labeled dose (25 mg ombitasvir/150 mg of paritaprevir/100 mg ritonavir) Length of Approval: Up to 12 weeks as determined by Table 1 Non-Preferred Agent(s) will be approved when the ONE of the following additional criteria are met: 1. The patient is currently being treated with the non-preferred agent OR 2. The patient has an FDA labeled contraindication, documented intolerance, or hypersensitivity to the preferred agent(s) OR 3. The prescriber has submitted documentation in support of the use of the non-preferred agent(s), for the intended diagnosis which has been reviewed and approved by the Clinical Review pharmacist Length of Approval: Up to 12 weeks as determined by Table 1 Table 1 Technivie Treatment Duration Recommendations based on FDA labeling Patient population Treatment Treatment Duration Genotype 4 without cirrhosis Technivie + ribavirin 12 weeks* *Technivie administered without ribavirin for 12 weeks may considered for treatment naïve-patients who cannot take or tolerate ribavirin Table 2 Agent(s) Technivie (ombitasvir/ paritaprevir/ritonavir) Contraindication(s) Patients with severe hepatic impairment (Child-Pugh C) Co-administration with drugs that are: highly dependent on CYP3A for clearance; moderate and strong inducers of CYP3A Known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis, Steven-Johnson syndrome) The contraindications to ribavirin also apply to this combination regimen (Technivie + ribavirin) MN_CS_HepC_2 nd Gen_PA_ProgSum_AR1115 Page 10 of 10