HEPATITIS WEB STUDY HEPATITIS C ONLINE Boceprevir Victrelis
HEPATITIS WEB STUDY HEPATITIS C ONLINE Boceprevir (Victrelis) Prepared by: David Spach, MD & H. Nina Kim, MD Last Updated: March 6, 2014 Hepatitis web study
BOCEPREVIR (VICTRELIS) Background and Dosing Hepatitis web study
Boceprevir (Victrelis) Summary • Approval: FDA Approved May 13, 2011 • Indications - Genotype 1 chronic HCV in combination with peginterferon-alfa and ribavirin - Adults (> 18 years of age) with compensated liver disease, including cirrhosis - Treatment-naïve or failed prior interferon and ribavirin therapy • Dosing - Available in 200 mg capsules - 800 mg three times daily (every 7 to 9 hours) with food (meal or light snack) - Boceprevir given for 24 -44 weeks - Treat with PR for 28 -48 weeks based on HCV RNA results (week 8 & 24) • Adverse Effects - Anemia, nausea, and dysgeusia Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
HCV Protein Processing Role of NS 3/4 A Serine Protease Polyprotein Precursor Signal Peptidase C E 1 E 2 p 7 NS 2/3 Protease NS 3/4 A Serine Protease NS 2 A NS 3 NS 4 B A NS 5 B Protein Processing Proteins C E 1 E 2 p 7 NS 2 NS 3 NS 4 A NS 4 B NS 5 A NS 5 B Hepatitis web study
HCV Protein Processing NS 3/4 A Serine Protease Inhibition Boceprevir NS 3/4 A Serine Protease Polyprotein Precursor C E 1 E 2 p 7 NS 2 NS 3 A NS 4 B NS 5 A B Proteins C E 1 E 2 p 7 NS 2 NS 3 A NS 4 B A NS 5 B Hepatitis web study
Boceprevir Treatment-Related HCV RNA Monitoring • Scheduled HCV RNA Monitoring - Pretreatment - Weeks 4, 8, 12, 24, at end of treatment, & during treatment follow-up • Recommended HCV RNA Assay* - Use sensitive real-time reverse transcriptase PCR assay - Lower limit of HCV quantification: < 25 IU/ml - Lower limit of HCV detection: approximately 9. 3 -15 IU/ml *For the purposes of assessing Response Guided Therapy milestones, a confirmed “detectable but below limit of quantification” HCV-RNA result should not be considered equivalent to an “undetectable” HCV-RNA result. Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir for Genotype 1 HCV Duration of Therapy HCV-RNA Results At Treatment Week 8 At Treatment 0 4 Week 24 Early Responder Previously Untreated Not detected Previous Partial Responders or Relapsers *Previous Null Responder Not detected Late Responder Detected Not detected Early Responder Not detected Regimen and Duration Not detected Late Responder Detected Not detected Detected or Not detected At Treatment Week 28 36 48 Boceprevir-24 PEG + Ribavirin-28 Boceprevir-32 PEG + Ribavirin-48 Boceprevir-32 PEG + Ribavirin-36 Boceprevir-32 PEG + Ribavirin-48 Boceprevir-44 PEG + Ribavirin-48 *Patients with compensated cirrhosis have same treatment schedule as Previous Null Responder Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir Response-Guided Therapy Previously Untreated Patients Boceprevir: Response Guided Therapy (RGT) for Previously Untreated Patients Boceprevir-24 wks Early Responder Peginterferon + Ribavirin-28 wks Boceprevir-32 wks Late Responder Peginterferon + Ribavirin-48 wks 10, 000 HCV RNA IU/ml 1, 000 Boceprevir Response-Guided Therapy Duration of therapy based on response at weeks 8 and 24 100, 000 1, 000 10 1 Undetectable -8 -4 0 4 8 12 16 20 24 Treatment Week 28 32 36 40 44 48 Hepatitis web study
Boceprevir Response-Guided Therapy Previous Partial Responders or Relapsers Boceprevir: Response Guided Therapy (RGT) for Previous Partial Responders or Relapsers Boceprevir-32 wks Early Responder Peginterferon + Ribavirin-36 wks Boceprevir-32 wks Late Responder Peginterferon + Ribavirin-48 wks 10, 000 HCV RNA IU/ml 1, 000 Boceprevir Response-Guided Therapy Duration of therapy based on response at weeks 8 and 24 100, 000 1, 000 10 1 Undetectable -8 -4 0 4 8 12 16 20 24 Treatment Week 28 32 36 40 44 48 Hepatitis web study
Boceprevir (Victrelis) Treatment Futility Rules for All Patients Futility Rules for Treatment with Boceprevir plus Peginterferon plus Ribavirin HCV RNA Results* Treatment Week Total Regimen and Duration 0 4 12 24 48 Boceprevir Week 12 HCV RNA > 100 IU/m. L 12 Weeks STOP PEG + RBV Week 24 HCV RNA Detectable (Confirmed) Boceprevir STOP 24 Weeks PEG + RBV *In clinical trials, HCV-RNA in plasma was measured using a Roche COBAS® Taq. Man® assay with a lower limit of quantification of 25 IU/m. L and a limit of detection of 9. 3 IU/m. L. Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
BOCEPREVIR (VICTRELIS) Adverse Effects Hepatitis web study
Boceprevir-Related Hematologic Adverse Effects Previously Untreated (SPRINT-1 & SPRINT-2) 60 50 Subjects (%) Peginterferon + Ribavirin (n = 467) 49 Peginterferon + Ribavirin + Boceprevir (n = 1225) 40 30 31 29 18 20 10 0 3 Hb < 10 8 6 Hb < 8. 5 Hemoglobin (g/d. L) 4 ANC < 750 ANC < 500 Neutrophils (x 106/L) 1 3 Plt < 50 0 <1 Plt < 25 Platelets (x 106/L) ANC = absolute neutrophil count Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir-Related Hematologic Adverse Effects Previously Treatment Failures (RESPOND-2) 60 50 Subjects (%) Peginterferon + Ribavirin (n = 80) 49 Peginterferon + Ribavirin + Boceprevir (n = 323) 40 30 26 25 20 10 10 13 4 1 0 Hb < 10 Hb < 8. 5 Hemoglobin (g/d. L) ANC < 750 7 ANC < 500 Neutrophils (x 106/L) 4 0 0 0 Plt < 50 Plt < 25 Platelets (x 106/L) ANC = absolute neutrophil count Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir-Related Hematologic Adverse Effects Previously Untreated (SPRINT-2) 100 Peginterferon + Ribavirin (n = 354) Peginterferon + Ribavirin + Boceprevir (n = 726) Patients (%) 80 60 50 40 31 20 4 0 Hemoglobin < 10 g/dl 7 Hemoglobin < 8. 5 g/dl Hemoglobin ANC = absolute neutrophil count Source: Sulkowski MS, et al. Hepatology. 2012: Oct 18 [Epub ahead of print]. Hepatitis web study
Boceprevir Adverse Effects in SPRINT Trial • Anemia - Nadir Hgb 8. 5 -10 g/d. L - 52 -63% in Boceprevir arms - 34% in Peginterferon/Ribavirin Control - 40% of patients used Epoetin alfa - Use of erythropoietin associated with treatment completion - Average attributable decrease in Hgb of 1 g/d. L • Dysgeusia - 21 -44% in all Boceprevir arms - 9% in Peginterferon/Ribavirin control arm Source: Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
BOCEPREVIR (VICTRELIS) Drug Interactions Hepatitis web study
Boceprevir Drug Interactions • Potential for Boceprevir to Affect Other Medications - Boceprevir is strong inhibitor of CYP 3 A 4/5 enzyme - Boceprevir is potential inhibitor of p-glycoprotein (P-gp) • Potential for Other Medications to Affect Boceprevir - Boceprevir primarily metabolized by aldo-ketoreductase (AKR) - Boceprevir may be co-administered with aldo-ketoreductase inhibitors - Partially metabolized by CYP 3 A 4/5 - Potential for interactions with drugs that inhibit or reduce CYP 3 A 4/5 Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir Dosage Adjustment in Special Populations • Hepatic Impairment - No dosage adjustment of Boceprevir with hepatic impairment • Renal Impairment/Dialysis - No dose adjustment of Boceprevir with any degree of renal impairment • Gender - No dosage adjustment of Boceprevir based on gender • Race - No dose adjustment of Boceprevir based on race • Age - No dosage adjustments of Boceprevir in subjects aged 19 -65 Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir Drug-Drug Interactions: Contraindicated Medications Contraindicated for use with Boceprevir Last Revised 1/20/2014 Drug Class Medication and Interaction Alpha-1 Adrenoreceptor Antagonist Alfuzosin, doxazosin, silodosin, tamsulosin Anticonvulsants Carbamazepine, phenobarbital, phenytoin Antimycobacterials Rifampin Ergot Derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine Gastrointestinal Motility Agent Cisapride Herbal Products St John’s wort (Hypericum perforatum) HMG Co. A-Reductase Inhibitors Lovastatin, simvastatin Neuroleptic Pimozide Oral Contraceptives Drospirenone PDE 5 Inhibitor Sildenafil or Tadalafil (dose levels for treatment of pulmonary hypertension) Sedatives/hypnotics Triazolam; orally administered midazolam Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir (Victrelis) Interactions with Antiretroviral Medications Boceprevir and Interactions with HIV Antiretroviral Medications Medication Effect Recommendation NNRTIs Efavirenz ↓ Boceprevir Avoid combination Etravirine ↓ Etravirine The clinical significance of the reductions in etravirine pharmacokinetic parameters has not been directly assessed Rilpivirine ↑ Rilpivirine No dose adjustment of boceprevir or rilpivirine is recommended. Integrase Inhibitors Raltegravir ↔ Raltegravir No dose adjustment required for boceprevir or raltegravir. Protease Inhibitors Atazanavir + Ritonavir Darunavir + Ritonavir Lopinavir + Ritonavir Atazanavir ↓ Ritonavir Coadministration of atazanavir/ritonavir and boceprevir is not recommended Darunavir ↓ Ritonavir ↓ Boceprevir Coadministration of darunavir/ritonavir and boceprevir is not recommended. Lopinavir ↓ Ritonavir ↓ Boceprevir Coadministration of lopinavir/ritonavir and boceprevir is not recommended. ↓ ↓ ↓ Source: Modified from Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
BOCEPREVIR (VICTRELIS) Resistance Hepatitis web study
Treatment Emergent NS 3 Protease Domain Mutations in Boceprevir-Treated Patients who Did Not Achieve SVR Frequency of Resistance-Associated Variants (RAVs) Detected Based on HCV Genotype >10% of Boceprevir-Treated Subjects who did not Achieve SVRa < 1 -10% of Boceprevir-Treated Subjects who did not Achieve SVRa a. Data Subjects with HCV Genotype 1 b V 36 M, T 54 S, R 155 K T 54 A, T 54 S, V 55 A, A 156 S, I/V 170 A V 36 A, T 54 A, V 55 I, V 107 I, R 155 T, A 156 S, A 156 T, V 158 I, D 168 N, I/V 170 T, I/V 170 F V 36 A, V 36 M, T 54 C, T 54 G, V 107 I, R 155 K, A 156 T, A 156 V, V 158 I, I/V 170 T, M 175 L taken from SPRINT-2 and RESPOND-2 Trials Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir for Chronic HCV Infection Resistance Among those who did not achieve SVR • Treatment-emergent resistance-associated variants (RAVs) occurred in 53% (295) of 343 evaluable subjects from SPRINT-2 and RESPOND-2 trials who did not achieve SVR, occurring more often among black patients and poor interferon responders. Frequency of Resistance-Associated Variants (RAVs) Detected Based on Interferon Response or Race Categories Subjects with samples sequenced, n Subjects with detectable RAVs, n/N (%) Poor Interferon Respondersa 169 115/169 (68%) Interferon Respondersb 128 40/128 (31%) Black Patients 47 30/47 (64%) Non-Black Patients 154 81/154 (53%) a. Subjects with < 1 -log 10 decrease in HCV-RNA at treatment week 4 from baseline b. Subjects with > 1 -log 10 decrease in HCV-RNA at treatment week 4 from baseline Source: Boceprevir (Victrelis) Prescribing Information. Merck & Co. Hepatitis web study
Boceprevir and Telaprevir Genotypic Resistance Mutation Telaprevir Boceprevir V 36 A/M + + T 54 S/A + + In vitro + Q 80 R/K - - R 155 K/T/Q + + A 156 S + + A 156 T/V + In vitro D 168 A/V/T/H - - In vitro + V 55 A V 170 A/T Source: Sarrazin C, Zeuzem S. Gastroenterology. 2010; 138: 447 -62. Hepatitis web study
BOCEPREVIR (VICTRELIS) Treatment Data Hepatitis web study
Boceprevir: Summary of Key Studies • Treatment-Naïve Genotype-1 - SPRINT-1: Phase 2 - SPRINT-2: Phase 3 • Previously Treated Genotype-1 - RESPOND-2: Phase 3 - PROVIDE: Phase 3 Hepatitis web study
Phase 2 Treatment Naïve Boceprevir with PEG + RBV in Genotype 1 SPRINT-1 Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-1 Trial: Part 1 SPRINT-1: Features § § § § N = 520 HCV-monoinfected patients Randomized, open label, phase 2 trial, with Part 1 and Part 2 All with chronic HCV genotype 1 and treatment naïve Eligible if 18 to 60 years of age Setting: 67 sites (US, Canada, and Europe) 90% with HCV RNA > 600, 000 IU/ml Part 1 (n = 520): Randomized to one of five arms Part 2 (n = 75): Randomized to one of two arms based on ribavirin dose Drug Dosing Boceprevir = 800 mg three times daily Peginterferon alfa-2 b = 1. 5 µg/kg once weekly Ribavirin = 800 -1400 mg/day (based on weight) Ribavirin = 400 -1000 mg/day (low dose) Source: Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-1 Trial, Part 1: Design Week 0 N=104 PR 48 4 12 24 28 48 Peginterferon + Ribavirin (weight-based) Boceprevir PR 4 PRB 24 Peginterferon + Ribavirin (weight-based) PR 28 Boceprevir PR 4 N=103 PRB 44 Peginterferon + Ribavirin (weight-based) N=103 N=107 PRB 28 N=103 PRB 48 Boceprevir Peginterferon + Ribavirin (weight-based) Source: Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-1 Trial, Part 1: Results SPRINT-1, Part 1: SVR 24 by Regimen Patients with SVR (%) 100 75 80 67 56 60 40 54 38 20 0 39/104 58/103 77/103 58/107 69/103 PR 48 PR 4/PRB 24 PR 4/PRB 44 PRB 28 PRB 48 B = Boceprevir; PR = Peginterferon + Ribavirin Source: Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
Boceprevir and Peginterferon plus Ribavirin for Chronic HCV SPRINT-1 Trial, Part 2: Design Week 0 N=16 PRB 48 N=59 Low-Dose 12 24 48 Boceprevir Peginterferon + Ribavirin (weight based) Boceprevir PRB 48 Peginterferon + Low-Dose Ribavirin (low dose) Source: Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
Boceprevir and Peginterferon plus Ribavirin for Chronic HCV SPRINT-1 Trial, Part 2, : Results SPRINT-1: SVR 24 by Ribavirin Dosing Patients with SVR (%) 100 80 60 50 36 40 20 0 8/16 21/59 PRB 48(weight-based Ribavirin) PRB 48(low-dose Ribavirin) P = Peginterferon; R = Ribavirin; B = Boceprevir Source: Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
Boceprevir and Peginterferon plus Ribavirin for Chronic HCV SPRINT-1 Trial: Conclusions Interpretation: “In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4 -week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. ” Source: Kwo PY, et al. Lancet. 2010; 376: 705 -16. Hepatitis web study
Phase 3 Treatment Naïve Boceprevir in Treatment Naive SPRINT-2 Poordad F, et al. N Engl J Med. 2011; 364: 1195 -206. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2 Trial: Study Design SPRINT-2: Study Features § N = 1097 HCV-monoinfected patients (159 black) § Randomized, double-blind, placebo-controlled, phase 3 study § All with chronic HCV and genotype 1 and treatment naïve § Setting: multiple sites in United States and Europe § HCV RNA > 10, 000 IU/ml § Mean age 50; 14. 5% black § Randomized to 3 arms (1: 1: 1) Drug Dosing Boceprevir = 800 mg three times daily Peginterferon alfa-2 b = 1. 5 µg/kg once weekly Ribavirin = 600 -1400 mg/day (based on weight) Source: Poordad F, et al. N Engl J Med. 2011; 364: 1195 -206. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2 Trial: Treatment Regimens Week 0 4 12 28 48 ✔ HCV RNA Lead In PR 48 24 Placebo Peginterferon + Ribavirin Undetectable HCV RNA at week 8 -24 Stop Therapy B 24 PR 28 -48 Boceprevir Peginterferon + Ribavirin Detectable HCV RNA at week 8 -24 Peginterferon + Ribavirin B 44 PR 48 Boceprevir Peginterferon + Ribavirin Source: Poordad F, et al. N Engl J Med. 2011; 364: 1195 -206. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2 Trial: Treatment Regimens SPRINT-2: SVR 24 by Regimen Patients with SVR (%) 100 80 63 66 60 40 38 20 0 137/163 233/368 242/366 PR 48 B 24/PR 28 -48 B 44/PR 48 B = Boceprevir; PR = Peginterferon + Ribavirin Source: Poordad F, et al. N Engl J Med. 2011; 364: 1195 -206. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2 Trial: Results SPRINT-2: SVR 24 by Regimen 100 Patients with SVR (%) PR 48 B 24/PR 28 -48 B 44/PR 48 80 63 67 66 60 40 68 53 42 38 40 23 20 0 137/163 233/368 242/366 All 12/52 29/55 Black 125/311 211/316 213/311 Nonblack SVR = Sustained Virologic Response; B = Boceprevir; PR = Peginterferon + Ribavirin Source: Poordad F, et al. N Engl J Med. 2011; 364: 1195 -206. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2 Trial: SVR by Liver Histology SPRINT-2: SVR 24 by Degree of Fibrosis 100 Patients with SVR (%) PR 48 B 24/PR 28 -48 80 67 67 B 44/PR 48 60 40 52 38 38 41 20 0 123/138 213/319 211/313 Metavir Score F 0, F 1, F 2 9/24 14/34 22/42 Metavir Score F 3 or F 4 Treatment Regimen PR 48 = Peginteron/Ribavirin x 48 weeks PR/T 12 = Peginteron/Ribavirin + Telaprevir x 12 weeks. PR = Peginterferon + Ribavirin SVR = Sustained Virologic Response; B = Boceprevir; Source: Poordad F, et al. N Engl J Med. 2011; 364: 1195 -206. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2 Trial: Conclusions: “The addition of boceprevir to standard therapy with peginterferon–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. ” Source: Poordad F, et al. N Engl J Med. 2011; 364: 1195 -206. Hepatitis web study
Phase 3 Treatment Experienced Boceprevir in Treatment Experienced RESPOND-2 Bacon BR, et al. N Engl J Med. 2011; 364: 1207 -17. Hepatitis web study
Boceprevir for Retreatment of HCV Genotype 1 Infection RESPOND-2 Trial: Study Design RESPOND-2: Study Features § § § § N = 403 HCV-monoinfected, treatment-experienced patients Randomized, double-blind, placebo-controlled, phase 3 study All with chronic HCV and genotype 1 Previously responded to treatment but did not obtain SVR Previous null responders excluded Mean Age = 53 88% with HCV RNA > 800, 000 IU/m. L Randomized to 3 arms (1: 2: 2) Drug Dosing Boceprevir = 800 mg three times daily Peginterferon alfa-2 b = 1. 5 µg/kg once weekly Ribavirin = 600 -1400 mg/day (based on weight) Source: Bacon BR, et al. N Engl J Med. 2011; 364: 1207 -17. Hepatitis web study
Boceprevir for Retreatment of HCV Genotype 1 Infection RESPOND-2 Trial: Treatment Regimens Week 0 4 Lead In PR 48 8 12 24 36 48 ✔HCV RNA ✔ Placebo Peginterferon + Ribavirin Undetectable HCV RNA at week 8 &12 Stop Therapy B 32 Boceprevir PR 36 -48 Peginterferon + Ribavirin Detectable HCV RNA at week 8, but Undetectable at week 12 Peginterferon + Ribavirin B 44 PR 48 Boceprevir Peginterferon + Ribavirin Source: Bacon BR, et al. N Engl J Med. 2011; 364: 1207 -17. Hepatitis web study
Boceprevir for Retreatment of HCV Genotype 1 Infection RESPOND-2 Trial: Results RESPOND-2: SVR 24 by Prior Response and Regimen PR 48 Patients with SVR (%) 100 80 59 60 0 B 44/PR 48 75 52 40 40 20 69 66 B 24/PR 28 -48 29 21 7 17/80 95/162 107/161 All 15/51 72/105 77/103 Prior Relapse 2/29 23/57 30/58 *Prior Nonresponse = decrease in HCV RNA of at least 2 logs by week 12, but detectable HCV RNA level during therapy period SVR = Sustained Virologic Response; B = Boceprevir; PR = Peginterferon + Ribavirin Source: Bacon BR, et al. N Engl J Med. 2011; 364: 1207 -17. Hepatitis web study
Boceprevir for Retreatment of HCV Genotype 1 Infection RESPOND-2 Trial: Results Based on Initial Week 4 Response RESPOND-2: SVR 24, by Initial Response and Regimen PR 48 Patients with SVR (%) 100 B 24/PR 28 -48 80 73 B 44/PR 48 79 60 40 33 34 25 20 0 0/12 0 15/46 15/44 *Poor Initial Response to PR 17/67 80/110 90/114 ^Good Initial Response to PR *Poor Initial Response to PR = decrease in HCV RNA level < 1 log 10 IU/ml after 4 week lead in ^Good Initial Response to PR = decrease in HCV RNA level > 1 log 10 IU/ml after 4 week lead in SVR = Sustained Virologic Response; B = Boceprevir; PR = Peginterferon + Ribavirin Source: Bacon BR, et al. N Engl J Med. 2011; 364: 1207 -17. Hepatitis web study
Boceprevir for Retreatment of HCV Genotype 1 Infection RESPOND-2 Trial: Conclusions: “The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon–ribavirin alone. ” Source: Bacon BR, et al. N Engl J Med. 2011; 364: 1207 -17. Hepatitis web study
Phase 3 Treatment Experienced Boceprevir for Patients with Prior Failure to PEG + RIB PROVIDE Vierling JM, et al. J Hepatol. 2013; Dec 19 [Epub ahead of print]. Hepatitis web study
Boceprevir for Patients with Prior Failure to PEG + RIB PROVIDE Study: Features PROVIDE: Study Features § § § § § N = 168 HCV-monoinfected, treatment-experienced patients Prior treatment failure to peginterferon + ribavirin Single arm, phase 3, multicenter, rollover study at 80 sites All with chronic HCV and genotype 1 Mean Age = 53 Genotype: GT 1 a = 68%; GT 1 b = 38% Race: 84% white; 13% black Fibrosis: 16% with Metavir F 3 or F 4 Prior Response: Null (31%), Partial (51%), Relapse (17%) All retreated with Boceprevir + Peginterferon alfa-2 b + Ribavirin Drug Dosing Boceprevir = 800 mg three times daily Peginterferon alfa-2 b = 1. 5 µg/kg once weekly Ribavirin = 600 -1400 mg/day (based on weight) Source: Vierling JM, et al. J Hepatol. 2013; Dec 19 [Epub ahead of print]. Hepatitis web study
Boceprevir for Patients with Prior Failure to PEG + RIB PROVIDE Study: Treatment Regimens Week 0 4 8 12 24 36 44 48 Patients who enrolled within 2 weeks after ending/completing previous treatment with PR B 44 PR 44 Boceprevir Peginterferon + Ribavirin Patients who enrolled ≥ 2 weeks after ending/completing their previous treatment with PR Boceprevir B 44 PR 48 Peginterferon + Ribavirin Lead In Source: Vierling JM, et al. J Hepatol. 2013; Dec 19 [Epub ahead of print]. Hepatitis web study
Boceprevir for Patients with Prior Failure to PEG + RIB PROVIDE Study: Results PROVIDE: SVR 24 by Prior Response (m. ITT) Patients with SVR 24 (%) 100 96 80 60 67 65 40 41 20 0 106/164 20/49 57/85 27/28 All Null Responders Partial Responders Relapsers SVR = Sustained Virologic Response; m. ITT = modfied intent to treat analysis Source: Vierling JM, et al. J Hepatol. 2013; Dec 19 [Epub ahead of print]. Hepatitis web study
Boceprevir for Patients with Prior Failure to PEG + RIB PROVIDE Study: Conclusions: “Re-treatment with boceprevir with peginterferon/ribavirin (BOC/PR) improved SVR rates in all patient subgroups, including those with prior null response. ” Source: Vierling JM, et al. J Hepatol. 2013; Dec 19 [Epub ahead of print]. Hepatitis web study
Phase 3 Treatment Naïve and Treatment Experienced Factors Predicting Response to Boceprevir in GT-1 SPRINT-2 and RESPOND-2 Trials Poordad F, et al. Gastroenterology. 2012: 143: 608 -18. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2: SVR Rates by IL 28 B rs 12979860 Genotype SPRINT-2: SVR 24 by rs 12979860 Genotype T/T 100 SVR (%) 65 55 60 40 27 C/C 82 78 80 C/T 80 71 59 28 20 0 10/37 33/116 50/64 23/42 67/103 63/77 26/44 82/115 44/55 PR 48 B 24/PR 28 -48 B 44/PR 48 Treatment Regimen SVR = Sustained Virologic Response; RGT = Response Guided Therapy PR = Peginterferon + Ribavirin; PRB = Peginterferon + Ribavirin + Boceprevir; Source: Poordad F, et al. Gastroenterology. 2012: 143: 608 -18. Hepatitis web study
Boceprevir for Retreatment of HCV Genotype 1 Infection RESPOND-2: SVR Rates by IL 28 B rs 12979860 Genotype RESPOND-2: SVR 12 by rs 12979860 Genotype T/T 100 79 SVR (%) 80 60 55 50 C/T C/C 72 73 13/18 48/66 77 61 46 40 17 20 0 5/10 5/29 PR 48 6/13 6/11 38/62 22/88 PRB-RGT 17/22 PR-48 B Treatment Regimen SVR = Sustained Virologic Response; RGT = Response Guided Therapy PR = Peginterferon + Ribavirin; PRB = Peginterferon + Ribavirin + Boceprevir; Source: Poordad F, et al. Gastroenterology. 2012: 143: 608 -18. Hepatitis web study
Boceprevir for Treatment-Naïve HCV Genotype 1 SPRINT-2 Trial: Conclusions: “The CC polymorphism at IL-28 B rs 12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥ 1 log 10 decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28 B. ” Source: Poordad F, et al. Gastroenterology. 2012: 143: 608 -18. Hepatitis web study
This slide deck is from the University of Washington’s Hepatitis C Online and Hepatitis Web Study projects. Hepatitis C Online www. hepatitisc. uw. edu Hepatitis Web Study http: //depts. washington. edu/hepstudy/ Funded by a grant from the Centers for Disease Control and Prevention. Hepatitis web study
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