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Hepatitisweb study
Hepatitis Web Study
Use of & Telaprevir (Incivek) in the Treatment of Chronic Hepatitis C Virus
Presentation Prepared by: David Spach, MD and Nina Kim, MDLast Updated: July 26, 2011
Hepatitisweb study
Hepatitisweb study
Background and DosingTelaprevir (Incivek)
HEPATITIS C: TREATMENT
Hepatitisweb study
Telaprevir (Incivek)
HEPATITIS C: TREATMENT
• Approval- FDA Approved May 23, 2011
• Indications- In combination with Peginterferon-alfa and Ribavirin (PR)- Chronic HCV genotype 1 infection- Adults (> 18 years of age) with compensated liver disease, including cirrhosis- Treatment-naïve or prior interferon-based treatment
• Dosing- 750 mg (two 375-mg tablets) three times daily with food (not low fat)- Treat with PR for 12 weeks (followed by additional 12 or 36 weeks PR)
• Adverse Effects- Rash, anemia, nausea, fatigue, headache, diarrhea, pruritus, and anal or rectal irritation and pain
Source: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals.
Hepatitisweb study
Dosing of Peginterferon-alfa and Ribavirin when Used with Telaprevir
HEPATITIS C: TREATMENT
Hepatitisweb study
*In clinical trials, HCV-RNA in plasma was measured using a COBAS® TaqMan® assay with a lower limit of quantification of 25 IU/mL and a limit of detection of 10 IU/mL.
Source: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals.
Telaprevir (Incivek)Response Guided Therapy
HEPATITIS C: TREATMENT
Hepatitisweb study
Telaprevir Response-Guided TherapyTreatment Naïve and Prior Relapse Patients
HEPATITIS C: TREATMENT
Telaprevir: Response Guided Therapy (RGT) for Treatment Naïve and Prior Relapse Patients
Undetectable
Telaprevir-12 wks
Peginterferon + Ribavirin-24 wks
Telaprevir-12 wks
Peginterferon + Ribavirin-48 wks
RGT
Hepatitisweb studySource: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals.
Telaprevir (Incivek)Treatment Futility Rules for All Patients
HEPATITIS C: TREATMENT
PR = Peginterferon + Ribavirin*In clinical trials, HCV-RNA in plasma was measured using a COBAS® TaqMan® assay with a lower limit of quantification of 25 IU/mL and a limit of detection of 10 IU/mL.
0 12 244
Hepatitisweb study
Hepatitisweb study
Adverse EffectsTelaprevir (Incivek)
HEPATITIS C: TREATMENT
Hepatitisweb studySource: Telaprevir (Incivek) Prescribing Information and Vertex Pharmaceuticals.
Telaprevir (Incivek)Adverse Effects
HEPATITIS C: TREATMENT
Hepatitisweb study
Hepatitisweb study
Telaprevir (Incivek)Mild Skin Rash
HEPATITIS C: TREATMENT
Source: Photograph Courtesy of John Scott, MD, University of Washington
Hepatitisweb study
Telaprevir (Incivek)Mild Skin Rash
HEPATITIS C: TREATMENT
• Assessment- Localized rash and/or rash with limited distribution- With or without associated pruritus
• Management- Continue all medications for HCV therapy- Use good skin care practices- Consider oral antihistamine + topical corticosteroid- Monitor and re-assess if progression occurs*
Source: Telaprevir (Incivek) Prescribing Information and Vertex Pharmaceuticals.
*Stop telaprevir if becomes severe or systemic symptoms develop; OK to continue Peginterferon and Ribavirin, but if rash persists within 7 days of stopping Telaprevir, consider sequential or simultaneous discontinuation of Peginterferon and Ribavirin
Hepatitisweb study
Telaprevir (Incivek)Good Skin Care for Telaprevir-Associated Rash
HEPATITIS C: TREATMENT
• Apply skin moisturizers at least twice a day • Avoid perfumes and other scented skin care products• Use hypoallergenic products• Keep hydrated• Wear loose-fitted clothing• Avoid scratching• Use unscented and mild laundry detergent• Avoid using dryer sheets with clothes in dryer• Limit sun exposure and use sun screen when out in sun• Avoid hot showers and hot baths• Consider using a nonsoap cleanser• Apply skin moisturizers after bathing (before drying off)
Source: Vertex Pharmaceuticals.
Hepatitisweb study
Hepatitisweb study
Telaprevir (Incivek)Moderate Skin Rash
HEPATITIS C: TREATMENT
Source: Photograph Courtesy of John Scott, MD, University of Washington
Hepatitisweb study
Telaprevir (Incivek)Moderate Skin Rash
HEPATITIS C: TREATMENT
• Assessment- Diffuse rash and/or rash with limited distribution- With or without superficial skin peeling, pruritus, or mucous membrane involvement with no ulceration
• Management- Continue all medications for HCV therapy- Use good skin care practices- Consider oral antihistamine + topical corticosteroid- Monitor and re-assess if progression occurs*
Source: Telaprevir (Incivek) Prescribing Information and Vertex Pharmaceuticals.
*Stop telaprevir if becomes severe or systemic symptoms develop; OK to continue Peginterferon and Ribavirin, but if does not improve within 7 days after stopping Telaprevir, consider sequential or simultaneous discontinuation of Peginterferon and Ribavirin
Hepatitisweb study
Hepatitisweb study
Telaprevir (Incivek)Severe Skin Rash
HEPATITIS C: TREATMENT
Source: Photograph Courtesy of John Scott, MD, University of Washington
Hepatitisweb study
Telaprevir (Incivek)Severe Skin Rash
HEPATITIS C: TREATMENT
• Assessment- Generalized rash with or without pruritus
OR- Rash with vesicles, bullae, or ulcerations (other than SJS)
• Management- Stop Telaprevir (do not restart)- May continue Peginterferon + Ribavirin- Use good skin care practices- Consider oral antihistamine + topical corticosteroid- Monitor and re-assess*
Source: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals.
*If rash does not improve within 7 days of stopping Telaprevir, consider sequential or simultaneous discontinuation of Peginterferon and Ribavirin
Hepatitisweb study
Telaprevir (Incivek)Serious Skin Rash (DRESS or SJS)
HEPATITIS C: TREATMENT
• Assessment- Stevens-Johnson Syndrome (SJS): Generalized rash with symptoms that may
include fever, target lesions, and mucosal erosions or ulcerationsOR
- Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): Presenting signs and systemic symptoms may include rash, fever, facial edema, and evidence of internal organ involvement (eg. hepatitis, nephritis). May occur with or without eosinophilia.
• Management- Stop all drugs immediately- Promptly refer for urgent medical care- Do NOT restart Telaprevir at any time in future
Source: Telaprevir (Incivek) Prescribing Information and Vertex Pharmaceuticals.
Hepatitisweb study
Hepatitisweb study
Drug InteractionsTelaprevir (Incivek)
HEPATITIS C: TREATMENT
Hepatitisweb studySource: Vertex Pharmaceuticals.
Telaprevir (Incivek)Drug-Drug Interactions: Contraindicated Medications
HEPATITIS C: TREATMENT
Hepatitisweb study
Hepatitisweb study
ResistanceTelaprevir (Incivek)
HEPATITIS C: TREATMENT
Hepatitisweb study
Viral Breakthrough & Telaprevir Resistance
HEPATITIS C: TREATMENT
• 14 (8.7%) viral breakthroughs were observed
• Half of these occurred before or at week 4
• Viral breakthroughs were more frequent in patients with HCV genotype 1a (11/14) than 1b (3/14).
• 11 (79%) of 14 patients with viral breakthrough had variants harboring mutations (V36M, V36M/R155K, or A156S) associated with decreased susceptibility to telaprevir
• No differences in number and type of mutations were observed across arms
Source: Marcellin P, et. al. Gastroenterology. 2011;140:459-68.
Hepatitisweb study
Telaprevir for Chronic HCV InfectionResistance Among those who did not Achieve SVR
HEPATITIS C: TREATMENT
• Treatment-emergent resistance mutations occurred in 62% of subjects from ADVANCE, ILLUMINATE and REALIZE trials who did not achieve SVR.
• Resistance mutations occurred in nearly 100% of subjects who failed during initial 12 weeks of triple therapy, and in majority of those who failed after 12 weeks or who relapsed.
• On-treatment virologic failure was more frequent in subjects with genotype 1A compared with 1B.
• On-treatment virologic failure was more frequent in subjects with prior history of null response.
Source: Vertex Pharmaceuticals.
Hepatitisweb study
Telaprevir for Chronic HCV InfectionResistance Among those who did not achieve SVR
HEPATITIS C: TREATMENT
• Treatment-emergent resistance mutations occurred in 62% of subjects from ADVANCE, ILLUMINATE and REALIZE trials who did not achieve SVR.
Source: Vertex Pharmaceuticals.
Hepatitisweb studySource: Sarrazin C, Zeuzem S. Gastroenterology. 2010;138:447-62.
Telaprevir and BoceprevirGenotypic Resistance
HEPATITIS C: TREATMENT
Mutation Telaprevir Boceprevir
V36A/M + +
T54S/A + +
V55A In vitro +
Q80R/K - -
R155K/T/Q + +
A156S + +
A156T/V + In vitro
D168A/V/T/H - -
V170A/T In vitro +
Hepatitisweb study
Hepatitisweb study
Treatment DataTelaprevir (Incivek)
HEPATITIS C: TREATMENT
Hepatitisweb study
Hepatitisweb study
HEPATITIS C: TREATMENT
Summary of Telaprevir (Incivek) Studies
• Telaprevir (Incivek) Studies in Treatment-Naïve- PROVE 1: Phase 2b- PROVE 2: Phase 2b - ADVANCE (Study 108): Phase 3 - ILLUMINATE (Study 111): Phase 3
• Telaprevir (Incivek) Studies in Previously Treated- PROVE 3: Phase 2b- REALIZE (Study C216): Phase 3
Hepatitisweb study
Hepatitisweb study
Telaprevir in Treatment NaivePROVE1
HEPATITIS C: TREATMENT
Hepatitisweb studySource: McHutchison JG, et. al. N Engl J Med. 2009;360:1827-38.
Telaprevir for Chronic Untreated HCV InfectionPROVE1: Study Design
HEPATITIS C: TREATMENT
Drug DosingTelaprevir = 1250 mg on day 1, then 750 mg tidPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/d for wt < 75 kg; 1200 mg/d for wt > 75 kg
Hepatitisweb study
Telaprevir (Incivek)Adverse Effects in Prove Trial
HEPATITIS C: TREATMENT
• Rash: Telaprevir versus Standard of Care- Overall incidence – 50% (TPV arms) vs 20% (PR controls)- Grade 3 (TPV versus PR Controls):
PROVE 1: 5-9% versus 1%PROVE 2: 3-7% versus 0%PROVE 3: 3-5% versus 0%
- Grade 4 (PROVE 3): 5% versus 0%
• Pruritus: 50-60%
• Anemia: Incremental Hgb decrease of ~1 g/dL
McHutchinson JG, et. al. N Engl J Med. 2009;360:1827-1838.Hezode C, et. al. N Engl J Med. 2009;360:1841-1850.McHutchinson JG, et. al. N Engl J Med. 2010;362:1292-1303.
Hepatitisweb study
PegIFN + RBV
Telaprevir
Source: McHutchison JG, et. al. N Engl J Med. 2009;360:1827-38.
Telaprevir for Chronic Untreated HCV InfectionPROVE1 Study: Treatment Regimens
HEPATITIS C: TREATMENT
PegIFN + RBV
Telaprevir
PegIFN + RBV
Telaprevir
PegIFN
T12PR12
T12PR24
T12PR48
PR48
12 24 48
N=17
N=79
N=79
N=75
Week 0
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionPROVE1 Study: Results
Percentage of Patients with SVR
Source: McHutchison JG, et. al. N Engl J Med. 2009;360:1827-38.
HEPATITIS C: TREATMENT
T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionPROVE1 Study: Results
Percentage of Patients with Relapse
Source: McHutchison JG, et. al. N Engl J Med. 2009;360:1827-38.
HEPATITIS C: TREATMENT
T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionPROVE1 Study: Results
Percentage of Patients with SVR and Relapse
Source: McHutchison JG, et. al. N Engl J Med. 2009;360:1827-38.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb studySource:McHutchison JG, et. al. N Engl J Med. 2009;360:1827-38.
Telaprevir for Chronic Untreated HCV InfectionPROVE1 Study: Conclusions
HEPATITIS C: TREATMENT
Conclusion: “Treatment with a telaprevir-based regimen significantly improved sustained virologic response rates in patients with genotype 1 HCV, albeit with higher rates of discontinuation because of adverse events.”
Hepatitisweb study
Hepatitisweb study
Telaprevir in Treatment NaivePROVE2
HEPATITIS C: TREATMENT
Hepatitisweb studySource: Hézode C, et al. N Engl J Med. 2009;360:1839-50.
Telaprevir for Chronic Untreated HCV InfectionPROVE2: Study Design
HEPATITIS C: TREATMENT
Drug DosingTelaprevir = 1250 mg on day 1, then 750 mg tidPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/d for wt < 75 kg; 1200 mg/d for wt > 75 kg
Hepatitisweb study
PegIFN + RBV
Telaprevir
Source: Hézode C, et al. N Engl J Med. 2009;360:1839-50.
Telaprevir for Chronic Untreated HCV InfectionPROVE2 Study: Treatment Regimens
HEPATITIS C: TREATMENT
PegIFN + RBV
Telaprevir
PegIFN + RBV
Telaprevir
PegIFN
T12PR12
T12PR24
T12P12
PR48
12 24 48
N=82
N=81
N=78
N=82
Week 0
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionPROVE2 Study: Results
Percentage of Patients with SVR
Source: Hézode C, et al. N Engl J Med. 2009;360:1839-50.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionPROVE2 Study: Results
Percentage of Patients with Relapse
Source: Hézode C, et al. N Engl J Med. 2009;360:1839-50.
HEPATITIS C: TREATMENT
T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionPROVE2 Study: Results
Percentage of Patients with SVR and Relapse
Source: Hézode C, et al. N Engl J Med. 2009;360:1839-50.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionPROVE2 Study: Results
Serious Adverse Events
Source: Hézode C, et al. N Engl J Med. 2009;360:1839-50.
HEPATITIS C: TREATMENT
T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb studySource: Hézode C, et al. N Engl J Med. 2009;360:1839-50.
Telaprevir for Chronic Untreated HCV InfectionPROVE2 Study: Conclusions
HEPATITIS C: TREATMENT
Conclusion: “In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin.”
Hepatitisweb study
Hepatitisweb study
Telaprevir in Treatment NaiveADVANCE
HEPATITIS C: TREATMENT
Hepatitisweb studySource: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Telaprevir for Chronic Untreated HCV InfectionADVANCE: Study Design
HEPATITIS C: TREATMENT
Drug DosingTelaprevir = 750 mg tidPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/d for wt < 75 kg; 1200 mg/d for wt > 75 kg
Hepatitisweb studySource: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Treatment Regimens
HEPATITIS C: TREATMENT
8 24 48Week 0
Telaprevir+
PegIFN + RBV
Placebo+
PegIFN + RBV
Telaprevir+
PegIFN + RBV
PegIFN + RBV
12
eRVR: PegIFN+ RBV
No eRVR: PegIFN + RBV
T8PR 24 or 48
T12PR 24 or 48
PR48
N =364
N =363
N =361
PegIFN+ RBV
eRVR: PegIFN + RBV
No eRVR: PegIFN + RBV
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Results
Percentage of Patients with SVR
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: RVR and eRVR Rates
Percentage of Patients with RVR and eRVR
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
T = Telaprevir; PR = Peginterferon + Ribavirin; RVR = rapid virologic response; eRVR = extended rapid virologic response
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Results According to eRVR
Percentage of Patients with SVR
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
T = Telaprevir; PR= Peginterferon + Ribavirin; SVR = Sustained Virologic ResponseeRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Results According to eRVR
Percentage of Patients with SVR
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin; eRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Results According to Race
Percentage of Patients with SVR
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Results According to Baseline HCV RNA
Percentage of Patients with SVR
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Results According to Liver Histology
Percentage of Patients with SVR
Source: Jacobson IM, et. al. Hepatology. 2010;52 (Supplement 1):427A. Abstract 211.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Adverse Effects
Adverse Effects: Anemia
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Adverse Effects
Percentage of Patients with Rash
Source: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
HEPATITIS C: TREATMENT
T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb studySource: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals.
Telaprevir in Treatment-Naïve Subjects (ADVANCE)SVR Rates by IL28B rs12979860 Genotype
HEPATITIS C: TREATMENT
PR48 = Peginteron/Ribavirin x 48 weeks PR/T12 = Peginteron/Ribavirin + Telaprevir x 12 weeks
Hepatitisweb studySource: Jacobson IM, et. al. N Engl J Med. 2011;364:2405-16.
Telaprevir for Chronic Untreated HCV InfectionADVANCE Study: Conclusions
HEPATITIS C: TREATMENT
Conclusion: “Telaprevir with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients.”
Hepatitisweb study
Hepatitisweb study
Telaprevir in Treatment NaiveILLUMINATE
HEPATITIS C: TREATMENT
Hepatitisweb studySource: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2.
Telaprevir for Chronic Untreated HCV InfectionILLUMINATE: Study Design
HEPATITIS C: TREATMENT
Drug DosingTelaprevir = 750 mg tidPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/d for wt < 75 kg; 1200 mg/d for wt > 75 kg
Hepatitisweb studySource: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2.
Telaprevir for Chronic Untreated HCV InfectionILLUMINATE Study: Treatment Regimens
HEPATITIS C: TREATMENT
48Week 0 12
Without eRVR
With eRVR
20 24
Telaprevir
PR
PR
PR
PR
T12PR 24 or 48
PR = Peginterferon + RibavirineRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)
eRVR (+)T12/PR24
eRVR (-)T12/PR48
eRVR (+)T12/PR48
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionILLUMINATE Study: Results
Percentage of Patients with SVR
Source: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2.
HEPATITIS C: TREATMENT
SVR = Sustained virologic response; T = Telaprevir; PR = Peginterferon + RibavirineRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)
Hepatitisweb study
Telaprevir for Chronic Untreated HCV InfectionILLUMINATE Study: Key Findings
HEPATITIS C: TREATMENT
• 24 weeks of Peg-IFN non-inferior to 48 weeks in patients with eRVR
• Overall SVR 72%- SVR 60% blacks- SVR 63% cirrhotics
• 88-92% of those who achieved eRVR achieved SVR
• 7% stopped treatment early due to virologic failure
• 17% stopped early due to fatigue or anemia
Source: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2.
Hepatitisweb studySource: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2.
Telaprevir for Chronic Untreated HCV InfectionILLUMINATE Study: Conclusions
HEPATITIS C: TREATMENT
Conclusion: “Among patients who achieved eRVR, a 24-week telaprevir-based regimen was noninferior to 48-week telaprevir-based regimen (92% SVR compared to 87.5%). Response-guided treatment led to 71.9% SVR overall and nearly two-thirds of the patients were eligible for shorter duration of treatment. Permanent discontinuation of all study drugs due to adverse events occurred in 17.4% of patients. Among eRVR randomized patients, there were moreadverse events and adverse event-related treatment discontinuationsin the 48-week versus 24-week arm. These results supportresponse-guided therapy for telaprevir-based regimens in treatment-naïve patients.”
Hepatitisweb study
Hepatitisweb study
HEPATITIS C: TREATMENT
Telaprevir in Treatment Experienced PROVE3
Hepatitisweb studySource: McHutchison JG, et al. N Engl J Med. 2010;362:1292-303.
Telaprevir for Previously Treated Chronic HCV InfectionPROVE 3 Study: Study Design
HEPATITIS C: TREATMENT
Drug DosingTelaprevir = 1125 mg on day 1, then 750 mg tidPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/d for wt < 75 kg; 1200 mg/d for wt > 75 kg
Hepatitisweb study
Peginterferon + Ribavirin
Telaprevir
Source: McHutchison JG, et al. N Engl J Med. 2010;362:1292-303.
Telaprevir for Previously Treated Chronic HCV InfectionPROVE 3 Study: Treatment Regimens
HEPATITIS C: TREATMENT
Peginterferon + Ribavirin
Telaprevir
Peginterferon + Ribavirin
Telaprevir
Peginterferon
T12
PR24
T24
PR48
T24
P24
PR48
N=115
N=113
N=111
N=114
12 24 480Week
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV InfectionPROVE 3 Study: Results
Percentage of Patients with SVR
Source: McHutchison JG, et al. N Engl J Med. 2010;362:1292-303.
HEPATITIS C: TREATMENT
SVR = sustained virologic response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV InfectionPROVE 3 Study: Results Based on Prior History
Percentage of Patients with SVR
Source: McHutchison JG, et al. N Engl J Med. 2010;362:1292-303.
HEPATITIS C: TREATMENT
SVR = sustained virologic response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV InfectionPROVE 3 Study: Results Based on Prior History
Percentage of Patients with SVR
Source: McHutchison JG, et al. N Engl J Med. 2010;362:1292-303.
HEPATITIS C: TREATMENT
SVR = sustained virologic response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV InfectionPROVE 3 Study: Results
Adverse Events
Source: McHutchison JG, et al. N Engl J Med. 2010;362:1292-303.
HEPATITIS C: TREATMENT
T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin
Hepatitisweb studySource: McHutchison JG, et al. N Engl J Med. 2010;362:1292-303.
Telaprevir for Previously Treated Chronic HCV InfectionPROVE 3 Study: Conclusions
HEPATITIS C: TREATMENT
Conclusion: “In this In HCV-infected patients in whom initial peginterferon alfa and ribavirin treatment failed, retreatment with telaprevir in combination with peginterferon alfa-2a and ribavirinwas more effective than retreatment with peginterferon alfa-2a and ribavirin alone.”
Hepatitisweb study
Hepatitisweb study
HEPATITIS C: TREATMENT
Telaprevir in Treatment Experienced REALIZE
Hepatitisweb studySource: Zeuzem S, et al. N Engl J Med. 2011;364:2417-28.
Telaprevir for Previously Treated Chronic HCV InfectionREALIZE Study: Study Design
HEPATITIS C: TREATMENT
Drug DosingTelaprevir = 750 mg q8hPeginterferon alfa-2a = 180 µg weeklyRibavirin = 1000 mg/d for wt < 75 kg; 1200 mg/d for wt > 75 kg
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV Infection (REALIZE) Definitions for Type of Previous Response to Peginterferon + Ribavirin
HEPATITIS C: TREATMENT
• No Response: Reduction of less than 2 log10 in HCV RNA after 12 weeks of therapy
• Partial Response: Reduction of 2 log10 or more in HCV RNA after 12 weeks of therapy, but with detectable HCV RNA
• Relapse: undetectable HCV RNA at the end of a previous course of therapy but HCV RNA positivity thereafter
Source: Zeuzem S, et al. N Engl J Med. 2011;364:2417-28.
Hepatitisweb study
Peginterferon + Ribavirin
Telaprevir
Source: Zeuzem S, et al. N Engl J Med. 2011;364:2417-28.
Telaprevir for Previously Treated Chronic HCV InfectionREALIZE: Treatment Regimens
HEPATITIS C: TREATMENT
Peginterferon + Ribavirin
Telaprevir
Peginterferon + Ribavirin
T12
PR36
T12
PR48
PR48
N=266
N=264
N=132
12 24 480Week 364 16
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV InfectionREALIZE Study: Results
Percentage of Patients with SVR
Source: Zeuzem S, et al. N Engl J Med. 2011;364:2417-28.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV InfectionREALIZE: Results Based on Prior History
Percentage of Patients with SVR
Source: Zeuzem S, et al. N Engl J Med. 2011;364:2417-28.
HEPATITIS C: TREATMENT
SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin
Hepatitisweb study
Telaprevir for Previously Treated Chronic HCV InfectionREALIZE: Adverse Effects
Adverse Effects: Anemia
Source: Zeuzem S, et al. N Engl J Med. 2011;364:2417-28.
HEPATITIS C: TREATMENT
T = Telaprevir; P = Peginterferon + Ribavirin
Hepatitisweb studySource: Zeuzem S, et al. N Engl J Med. 2011;364:2417-28.
Telaprevir for Previously Treated Chronic HCV InfectionREALIZE Study: Conclusions
HEPATITIS C: TREATMENT
Conclusion: “Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase.”
Hepatitisweb studySource: Vertex Pharmaceuticals.
Telaprevir in Previously Treated Subjects (REALIZE)SVR Rates by IL28B rs12979860 Genotype
HEPATITIS C: TREATMENT
PR48 = Peginteron/Ribavirin x 48 weeks PR/T12 = Peginteron/Ribavirin + Telaprevir x 12 weeks
Hepatitisweb study
Hepatitisweb study
Questions?
HEPATITIS C: TREATMENT