Express Scripts, Inc. monograph dated 5/25/2011; selected revision 6/1/2011

Transcription

1 BENEFIT DESCRIPTION AND LIMITATIONS OF COVERAGE ITEM: PRODUCT LINES: COVERED UNDER: DESCRIPTION: CPT/HCPCS Code: Company Supplying: Setting: Coverage Criteria: Approval Period: Victrelis (boceprevir capsules) Commercial HMO/PPO/CDHP HMO: Rx PPO/CDHP: Rx Binds reversibly to nonstructural protein 3 (NS 3) serine protease and inhibits replication of the hepatitis C virus. Considered a direct-acting antiviral treatment for HCV, also called a specifically targeted antiviral therapy for HCV (STAT-C). J8499 Merck Oral Rx Express Scripts, Inc. monograph dated 5/25/2011; selected revision 6/1/2011 As stated by indication Recommended Authorization Criteria Coverage of boceprevir is recommended for use in combination with peginterferon alfa and ribavirin in those who meet the following criteria: FDA-Approved Indication 1. Treatment-naïve adult patients with chronic HCV genotype 1 monoinfection without cirrhosis. Approve 8 weeks of boceprevir in patients who meet the following criteria a, b, c and d. These patients will be assessed again for response in 4 weeks (TW 12) and again in 16 weeks (TW 24). Note: Patients must have at least a baseline, TW 4, TW 8, TW 12 and TW 24 HCV RNA titer since this will be used to assess response and further authorization. a) Boceprevir is prescribed by or in consultation with a gastroenterologist or infectious disease b) The patient has completed, or will be completing, a 4-week lead-in with peginterferon alfa (i.e., peginterferon alfa-2b [PegIntron ] or peginterferon alfa-2a [Pegasys ]) and ribavirin prior to initiating boceprevir, and c) If the patient has completed the 4-week lead in, the patient has had a 1 log 10 reduction in HCV RNA from baseline at TW 4 (meaning TW 4 HCV RNA has been reduced by at least 1 log10 from baseline) [For patients with < 1 log 10 reduction in HCV RNA from baseline at TW 4 see criteria (4)], and d) Boceprevir is prescribed in combination with PR (triple-drug therapy). is in addition to the 8 weeks of boceprevir the patient has already received (for 20 weeks of triple-drug therapy). These patients will be assessed again for a response in 12 weeks (TW 24). 1

2 ii) Patients with HCV RNA 100 IU/mL at TW 12. No further authorization for boceprevir is recommended. Product labeling recommends discontinuing triple-drug therapy in patients with HCV RNA results > 100 IU/mL at TW 12. The viral titer is assessed at TW24 (4-week PR lead-in plus 20 weeks of boceprevir/pr). (1) Patients (early responder [HCV RNA undetectable at TW 8]) with undetectable HCV RNA at TW 24. Approve boceprevir using criteria (1)(a) and (1)(b). (a) Non-Black patients. Approve boceprevir for 4 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received. These patients receive 24 weeks of triple-drug therapy following the 4-week lead-in (total treatment duration 28 weeks). (b) Black patients. Approve boceprevir for 24 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has already received. These patients receive 44 weeks of triple-drug therapy following the 4-week lead-in (4-week lead-in, 44 weeks of triple-drug therapy). The total duration of treatment is 48 weeks. In the opinion of an expert reviewing the data we have adopted this criterion. (2) Patients (late responder [HCV RNA detectable at TW 8]) with undetectable HCV RNA at TW 24. Approve boceprevir using criteria (2)(a) and (2)(b). (a) Non-Black patients. Approve boceprevir for 12 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received. These patients receive 32 weeks of triple-drug therapy following the 4-week lead-in. In addition, after completing 32 weeks of triple-drug therapy (TW 36), patients receive 12 weeks of PR therapy (4- week lead-in, 32 weeks triple-drug therapy, 12 weeks of PR). The total duration of treatment is 48 weeks. (b) Black patients. Approve boceprevir for 24 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has already received. These patients receive 44 weeks of triple-drug therapy following the 4-week lead-in (4-week lead-in, 44 weeks of triple-drug therapy). The total duration of treatment is 48 weeks. In the opinion of an expert reviewing the data we have adopted this criterion. (3) Patients (early or late responder) with detectable HCV RNA at TW 24. No further authorization for boceprevir is recommended. Product labeling for boceprevir recommends discontinuing therapy in patients with detectable HCV RNA at TW 24. In treatment-naïve patients without cirrhosis, the FDA-approved labeling recommends RGT based on ontreatment virologc response at TW 8 and TW 24 (early- or late-response). Patients with undetectable HCV RNA at TW 8 (early responders) will receive a total of 24 weeks of triple-drug therapy following the 4-week lead-in with PR. In SPRINT-2, the proportions of patients (Black and non-black cohorts) with undetectable HCV RNA at TW 8 who had SVR were high irrespective of the treatment regimen; however early-response occurred almost three times as often in the boceprevir groups (RGT n = 208/368; FDT n = 204/366) as in the PR group (n = 60/363). For patients assigned to boceprevir RGT, SVR among early responders was 88%, whereas for patients with detectable HCV RNA at TW 8 SVR was 36%. SVR in the fixed duration treatment arm (44 weeks of triple-drug therapy after 4- week lead-in) was 90% and 40%, for early responders and late responders, respectively. Therefore, in patients with early-response, additional weeks of boceprevir did not appear to confer any additional benefit in terms of SVR. The FDA approved dosing in late responders (detectable HCV RNA at TW 8) differs from the pivotal study. The approved duration of therapy for patients with late-response is 32 weeks of triple-drug therapy followed by 12 weeks of PR alone for a total treatment duration of 48 weeks. For late responders in SPRINT-2 (Black and non-black cohorts) SVR was achieved in 72% of patients with a detectable HCV RNA between TW 8 and up to TW 24 (not including Week 24), assigned to RGT (24 weeks of triple-drug therapy). (Note: This analysis did not 2

3 include patients who discontinued therapy at TW 28 [early responders] or those who discontinued for futility at TW 24). For patients assigned to FDT (44 weeks of triple-drug therapy) with a detectable HCV RNA between TW 8 and up to TW 24 (not including Week 24), the rate of SVR was 75%. The boceprevir product labeling does not specifically address Black vs. non-black patients; however, data support a longer duration of therapy in Black patients. In SPRINT-2 overall rates of SVR in the Black cohort were statistically significantly better for both the boceprevir containing arms vs. PR; a numerically smaller proportion (~10%) of Black patients assigned to RGT vs. FDT, achieved SVR (42% vs. 53%, respectively). Boceprevir should be discontinued in any patients with HCV RNA _ 100 IU/mL at TW 12 or with detectable HCV RNA at TW 24. No patients in SPRINT-2 with detectable HCV RNA at TW 24 were continued on therapy. Guidelines from the American Association for the Study of Liver Diseases (AASLD 2009) recommend discontinuing therapy at TW 24 in patients who do not achieve a complete EVR and if HCV RNA remains positive at TW Retreatment. Adult patients with chronic HCV genotype 1 monoinfection who have been previously treated (partial-responders and relapsers, only) for HCV with interferon alfa or peginterferon alfa without cirrhosis. A partial-response is defined as a 2 log 10 reduction in HCV RNA by TW 12, but without SVR. Relapse is defined as HCV RNA undetectable at the end of treatment, but becomes detectable after treatment (SVR is not achieved). Examples of medications that may have been previously used are the interferons (Intron A, Roferon A, Pegasys, PEGIntron) with or without ribavirin. Approve 8 weeks of boceprevir in patients who meet the following criteria a, b, c, and d. These patients will be assessed again for response in 4 weeks (TW 12) and again in 16 weeks (TW 24). Note: Patients must have at least a baseline, TW 4, 8, 12, and 24 HCV RNA titer since this will be used to assess response and further authorization. a) Boceprevir is prescribed by of in consultation with a gastroenterologist or infectious disease b) The patient has completed, or will be completing, a 4-week lead-in with peginterferon alfa (i.e., peginterferon alfa-2b [PegIntron] or peginterferon alfa-2a [Pegasys]) and ribavirin prior to initiating boceprevir, and c) If the patient has completed the 4-week lead in, the patient has had a _ 1 log10 reduction in HCV RNA from baseline at TW 4 (meaning TW 4 HCV RNA has been reduced by at least 1 log10 from baseline) [For patients with < 1 log10 reduction in HCV RNA from baseline at TW 4 see criteria (4)], and d) Boceprevir is prescribed in combination with PR (triple-drug therapy). is in addition to 8 weeks of boceprevir the patient has received (for 20 weeks of triple-drug therapy). These patients will be assessed again for a response in 12 weeks (TW 24). ii) Patients with HCV RNA 100 IU/mL at TW 12. No further authorization for boceprevir is recommended. Product labeling recommends to discontinue triple-drug therapy in patients with HCV RNA results > 100 IU/mL at TW 12. The viral titer is assessed at TW 24 (after 4-week PR lead-in plus 20 weeks of boceprevir/pr) (1) Patients (early responder [HCV RNA undetectable at TW 8]) with undetectable HCV RNA at TW 24. Approve boceprevir using criteria (1)(a) and (2)(b). (a) Non-black patient. Approve boceprevir for 12 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received (for 32 weeks of triple-drug therapy). 3

4 (b) These patients receive 32 weeks of triple-drug therapy following the 4-week lead-in (total treatment duration 36 weeks). Black patient. Approve boceprevir for 24 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received. These patients receive 44 weeks of triple-drug therapy following the 4-week lead-in (total treatment duration 48 weeks). In the opinion of an expert reviewing the data we have adopted this criterion. (2) Patients (late responder [HCV RNA detectable at TW 8]) with undetectable HCV RNA at TW 24. Approve boceprevir using criteria (2)(a) and (2)(b). (a) Non-black patient. Approve boceprevir for 12 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received. These patients receive 32 weeks of triple-drug therapy following the 4-week lead-in. In addition, patients receive 12 weeks of PR following completion of triple-drug therapy (4-week lead-in, 32 weeks triple-drug therapy, 12 weeks PR) for a total duration of treatment of 48 weeks. (b) Black patient. Approve boceprevir for 24 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has already received. These patients receive 44 weeks of triple-drug therapy following the 4-week lead-in (total treatment duration 48 weeks). In the opinion of an expert reviewing the data we have adopted this criterion. (3) Patients (early or late responder) with detectable HCV RNA at TW 24. No further authorization is recommended. Product labeling recommends discontinuing triple-drug therapy in patients with confirmed detectable HCV RNA at TW 24. Boceprevir product labeling recommends RGT in prior relapsers and partial non-responders. The recommended duration of therapy in prior relapsers and non-responders is based on virologic response at TW 8 and TW 24 (early- or late-response). For patients with earlyresponse, triple-drug therapy is administered for 32 weeks, and the total duration of treatment is 36 weeks. In patients with late-response, triple-drug therapy is administered for 32 weeks, and is followed by PR alone for 12 weeks for a total treatment duration of 48 weeks. In RESPOND-2, the duration of therapy was based on a treatment decision at TW 8 at which time patients with an undetectable HCV RNA were eligible for a shorter duration of therapy. Early responders had a similar rate of SVR whether boceprevir was administered for 32 (RGT) or 44 (FDT) weeks. The proportions of patients with an undetectable HCV RNA at TW 8 were greater in boceprevir RGT and FDT groups (46% [n = 74/162] and 52% [n = 84/161], respectively) vs. PR (9% [n = 7/80]). Early response was associated with a high rate of SVR regardless of assigned treatment (RGT [86%], FDT [88%], or PR [100%]). Overall SVR rates for RGT, FDT and control were 59%, 66% and 21%, respectively. Although SVR was achieved in 12 more patients assigned to FDT than RGT (n = 107 and n = 95, respectively), the rates of SVR (66% and 59%, respectively) did not differ significantly (odds ratio [OR] of SVR for FDT vs. RGT = 1.4; 95% CI: 0.9, 2.2). Boceprevir product labeling does not provide separate dosing recommendations for Black and non-black patients. The retreatment trial, RESPOND-2, did not enroll a large number of Black patients (n = 38; 9%) therefore it is difficult to know the optimal treatment duration in prior treatment failure patients in this cohort. A subgroup analysis of the small number of Black patients enrolled in the study reported SVR rates of 53% and 61% for boceprevir FDT and RGT groups, respectively. In SPRINT-2, treatment-naïve Black patients assigned to RGT had numerically (about 10%) lower rates of SVR than patients assigned to FDT with boceprevir. 3. Retreatment. Adult patients with chronic HCV genotype 1 monoinfection who have been previously treated (historical null-responders, only) for HCV with interferon alfa or peginterferon alfa without cirrhosis. Null-responders are patients with a documented < 4

5 2 log10 reduction in HCV RNA by TW 12 of a previous course of PR. Examples of medications that may have been previously used are the interferons (Intron A, Roferon A, Pegasys, PEGIntron) with or without ribavirin. Approve 8 weeks of boceprevir in patients who meet the following criteria a, b, c and d. These patients will be assessed again for response in, 4 weeks (TW 12) and again in 16 weeks (TW 24). Note: Patients must have at least a baseline, TW 12, and TW 24 HCV RNA titer since this will be used to assess response and further authorization. a) Boceprevir is prescribed by or in consultation with a gastroenterologist or infectious disease b) The patient has completed, or will be completing, a 4-week lead-in with peginterferon alfa (i.e., peginterferon alfa-2b [PegIntron] or peginterferon alfa-2a [Pegasys]) and ribavirin prior to initiating boceprevir, and c) The patient is a documented prior null-responder (< 2 log10 reduction in HCV RNA at TW 12 of a prior course of interferon/peginterferon therapy for HCV), and d) Boceprevir is prescribed in combination with PR (triple-drug therapy). is in addition to 8 weeks of boceprevir the patients has received (for 20 weeks of tripledrug therapy). These patients will be assessed again for a response in 12 weeks (TW 24). ii) Patients HCV RNA 100 IU/mL at TW 12. No further authorization for boceprevir is recommended. Product labeling recommends discontinuing triple-drug therapy in patients with HCV RNA results 100 IU/mL at TW 12. The viral titer is assessed at TW 24 (after 4-week PR lead-in plus 20 weeks of boceprevir/pr) (1) Patients with undetectable HCV RNA at TW 24. Approve boceprevir for 24 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received. These patients receive 44 weeks of triple-drug therapy following the 4-week lead-in (total treatment duration 48 weeks). (2) Patients with detectable HCV RNA at TW 24. No further authorization for boceprevir is recommended. Product labeling recommends discontinuing triple-drug therapy in patients with confirmed detectable HCV RNA at TW 24. Boceprevir has not been prospectively studied in patients documented to be historical nullresponders (< 2 log 10 decline in HCV RNA by TW 12 of prior therapy). The clinical studies included patients who were poorly interferon responsive, defined by the manufacturer as patients with < 0.5 log 10 HCV RNA decline in viral load at TW 4 with PR alone. In treatmentnaïve patients with < 0.5 log 10 decline in viral load at TW 4, SVR was achieved in 30% (11/37), 28% (13/47), and 0% (0/25) of patients in the boceprevir FDT, RGT and PR groups, respectively. Patients with < 0.5 log 10 decline in HCV RNA by TW 4 are predicted to have a null-response to PR at TW 12. Because RGT was not studied in prior null-responders, if considered for treatment, these patients should receive 4 weeks of PR followed by 44 weeks of boceprevir/pr. 4. Poor interferon response. Adult patients with chronic HCV genotype 1 monoinfection and <1 log 10 reduction HCV RNA after TW 4 (4-week PR lead-in) without cirrhosis. Approve 8 weeks of boceprevir in patients who meet the following criteria a, b, c, and d. These patients will be assessed again for response in, 4 weeks (TW 12) and again in 16 weeks (TW 24). Note: Patients must have at least a baseline, TW 4, TW 12, and TW 24 HCV RNA titer since this will be used to assess response and further authorization. 5

6 a) Boceprevir is prescribed by or in consultation with a gastroenterologist or infectious disease b) The patient has completed a 4-week lead-in with peginterferon alfa (i.e., peginterferon alfa-2b [PegIntron] or peginterferon alfa-2a [Pegasys]) and ribavirin prior to initiating boceprevir, and c) The patient has had a < 1 log 10 reduction in HCV RNA from baseline at TW 4 (meaning TW 4 HCV RNA has been reduced by less than 1 log 10 from baseline), and d) Boceprevir is prescribed in combination with PR (triple-drug therapy). is in addition to 8 weeks of boceprevir the patient has received (for 20 weeks of triple-drug therapy). These patients will be assessed again for a response in 12 weeks (TW 24). ii) Patients HCV RNA 100 IU/mL at TW 12. No further authorization for boceprevir is recommended. Product labeling recommends to discontinue triple-drug therapy in patients with HCV RNA results 100 IU/mL at TW 12. The viral titer is assessed at TW 24 (after 4-week PR lead-in plus 20 weeks of B/PR). (1) Patients with undetectable HCV RNA at TW 24. Approve boceprevir for 24 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received. These patients receive 44 weeks of triple-drug therapy following the 4-week lead-in (total treatment duration 48 weeks). (2) Patients with detectable HCV RNA at TW 24. No further authorization for boceprevir is recommended. Product labeling recommends discontinuing triple-drug therapy in patients with confirmed detectable HCV RNA at TW 24. Poorly interferon responsive patients (< 1 log 10 decline in HCV RNA at TW 4) who were treated with boceprevir/pr have a lower likelihood of achieving SVR, and a higher rate of detection of resistanceassociated substitutions upon treatment failure, compared to patients with a greater interferon response. Although lower rates of SVR were achieved in previously untreated patients in SPRINT-2 who demonstrated poor interferon responsiveness, SVR was still achieved in a significantly greater proportion of patients in boceprevir-treated groups compared with PR and SVR was achieved in 38% (36/95), 28% (27/97), and 4% (3/83) in the boceprevir FDT, RGT and PR groups, respectively. Boceprevir labeling recommends to consider treating previously untreated patients who are poorly interferon responsive (as determined by TW 4 HCV RNA) with boceprevir/pr for 44 weeks in order to maximize rates of SVR. No recommendation in retreatment patients who are poorly interferon responsive is provided in product labeling. In subanalyses of the RESPOND-2 (retreatment) trial, patients with poor interferon response at TW 4 treated with boceprevir/pr still had significantly higher rates of SVR as compared with PR alone. In patients who were previous relapsers or non-responders and with poor interferon response at TW 4 overall rates of SVR were 34% (15/44), 33% (15/46) and 0% (0/12) in the boceprevir FDT, RGT and PR groups, respectively. 5. Adult patients with chronic HCV genotype 1 monoinfection and advanced fibrosis/ compensated cirrhosis. Approve 8 weeks of boceprevir in patients who meet the following criteria a, b, and c. These patients will be assessed again for response in, 4 weeks (TW 12) and again in 12 weeks (TW 24). Note: Patients must have at least a baseline, TW 12, and TW 24 HCV RNA titer since this will be used to assess response and further authorization. In the opinion of an expert reviewing the data we have adopted this criterion. a) Boceprevir is prescribed by or in consultation with a gastroenterologist or infectious disease 6

7 b) The patient has completed, or will be completing, a 4-week lead-in with peginterferon alfa (i.e., peginterferon alfa-2b [PegIntron] or peginterferon alfa-2a [Pegasys]) and ribavirin prior to initiating boceprevir, and c) Boceprevir is prescribed in combination with PR (triple-drug therapy). is in addition to 8 weeks of boceprevir the patient has received (for 20 weeks of triple-drug therapy). These patients will be assessed again for a response in 12 weeks (TW 24). ii) Patients HCV RNA 100 IU/mL at TW 12. No further authorization for boceprevir is recommended. Product labeling recommends discontinuing triple-drug therapy in patients with HCV RNA results > 100 IU/mL at TW 12. The viral titer is assessed at TW 24 (after 4-week PR lead-in plus 20 weeks of boceprevir/pr) (1) Patients with undetectable HCV RNA at TW 24. Approve boceprevir for 24 weeks. This is in addition to 20 weeks of triple-drug therapy the patient has received. These patients receive 44 weeks of triple-drug therapy following the 4-week lead-in (total treatment duration 48 weeks). (2) Patients with detectable HCV RNA at TW 24. No further authorization for boceprevir is recommended. Product labeling recommends discontinuing triple-drug therapy in patients with confirmed detectable HCV RNA at TW 24. Product labeling for boceprevir recommends 44 weeks of triple-drug therapy in patients with compensated cirrhosis. SPRINT-2 enrolled 100 patients with baseline Metavir F 3/4 who received at least one dose of any study medication. The proportion of patients with Metavir F 3/4 in FDT, RGT and PR groups were 11% (n = 42), 9% (n = 34), and 7% (n = 24), respectively. Overall rates of SVR in patients with Metavir 3/4 at baseline were not statistically significantly different between the FDT, RGT and PR groups (52%, 41%, and 38%, respectively; P = 0.31 for FDT vs. PR and P = 1.00 for RGT vs. PR). A subgroup analysis [abstract] of the boceprevir pivotal trials, SPRINT-2 and RESPOND-2, reported boceprevir triple-drug therapy was safe and effective in treatment naive and previously treated patients with chronic HCV genotype 1 infection with advanced fibrosis/cirrhosis ([Metavir F 3/4] n = 178). The results reported in the abstract are in accordance with those of pivotal SPRINT-2 trial above, with the exception that the difference between FDT and PR in patients with baseline Metavir F 3/4 was reported as statistically significant (P < 0.035). The RESPOND-2 trial, enrolled 78 patients with Metavir F 3/4; in the FDT, RGT, and PR groups, the respective numbers (%) of patients with Metavir F 3/4 were n = 31 (19%), n = 32 (20%) and n = 15 (19%). In a subanalysis, the odds of SVR were not significantly different for patients with Metavir F 3/4 between RGT and FDT treatment arms, although a numerically greater proportion of patients in the FDT (67.7% [ n = 21/31]) vs. RGT (43.8% [14/32]), achieved SVR. A subgroup analysis [abstract] of the boceprevir pivotal trials, SPRINT-2 and RESPOND-2, reported SVR in 13.3% of patients with Metavir F 3/4 assigned to PR (P < 0.04 for RGT vs. PR and P < for FDT vs. PR). Other Uses with Supportive Evidence 6. Adult patients with Hepatitis B virus (HBV)/chronic HCV genotype 1 co-infection. Approve boceprevir using appropriate FDA-approved indications (above) for monoinfected patients. There are no data on the use of boceprevir in patients with HBV/HCV co-infection. In the expert opinion of a reviewer we have adopted this criterion. 7

8 Exclusions Coverage of boceprevir is not recommended in the following circumstances: 1. Patients with non-genotype 1 chronic HCV infection. The safety and efficacy of boceprevir in patients with non-genotype 1 HCV infection have not been established. Boceprevir acts only on HCV genotype 1 protease and would not be expected to have effect on other hepatitis C viral genotypes. 2. Patients with chronic HCV and human immune deficiency (HIV) co-infection. Although currently under investigation, the safety and efficacy of boceprevir in patients with HCV/HIV co-infection have not been established. The optimal duration of therapy is unknown. Boceprevir should not be used in patients with HCV/HIV co-infection outside of carefully designed clinical trials. Fully published data are needed to determine the efficacy and safety of boceprevir in patients with HCV/HIV co-infection. In the opinion of an expert reviewing the data, we have adopted this criterion. 3. Patients with recurrent hepatitis C after liver (or other organ) transplantation. There are no data available on the use of boceprevir in patients after liver or other organ transplants. In the expert opinion of a reviewer we have adopted this criterion. 4. Monotherapy with boceprevir. Boceprevir monotherapy, that is, boceprevir not concomitantly prescribed with PR cannot be recommended. Rapid emergence of resistance has been reported when oral protease inhibitors such as boceprevir are used without PR. The protease inhibitors (e.g., boceprevir) have a low genetic barrier to resistance and they have been shown to select resistant HCV variants in vitro. There are no indications for boceprevir monotherapy. Boceprevir must be prescribed in combination with peginterferon and ribavirin. 5. Pediatric patients (age < 18 years). Boceprevir has not been studied in pediatric patients and is not indicated for use in patients < 18 years of age. In the expert opinion of a reviewer we have adopted this criterion. 6. Patient has failed therapy with boceprevir or another NS3/4A protease inhibitor for HCV (e.g., telaprevir). Efficacy has not been established in patients who have previously failed therapy with a treatment regimen that includes boceprevir or other HCV NS3/4A protease inhibitors (e.g., telaprevir). Many of the treatment-emergent NS3 amino acid substitutions detected in boceprevir-treated subjects who did not achieve SVR in the Phase III clinical trials have been demonstrated to reduce the anti-hcv activity of other HCV NS3/4A protease inhibitors. The impact of prior exposure to boceprevir or treatment failure on the efficacy of other HCV NS3/4A protease inhibitors (e.g., telaprevir) has not been studied. The efficacy of boceprevir has not been established for patients with a history of exposure to other NS3/4A protease inhibitors. 7. Coverage is not recommended for circumstances not listed in the Recommended Authorization Criteria. Criteria will be updated as new published data are available. APPROVAL: ENDORSED BY: Pharmacy & Therapeutics Committee Original Date: 7/20/2011 APPROVED BY: Date: 8