Hepatitis web study H EPATITIS W EB S TUDY Use of & Telaprevir (Incivek) in the Treatment of Chronic Hepatitis C Virus Presentation Prepared by: David Spach, MD and Nina Kim, MD Last Updated: July 26, 2011

Hepatitis web study Hepatitis web study Background and Dosing T ELAPREVIR (I NCIVEK ) HEPATITIS C: TREATMENT

Hepatitis web 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 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.

Hepatitis web study Dosing of Peginterferon-alfa and Ribavirin when Used with Telaprevir HEPATITIS C: TREATMENT

Hepatitis web 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

Hepatitis web study Telaprevir Response-Guided Therapy Treatment 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

Hepatitis web study Source: 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

Hepatitis web study Hepatitis web study Adverse Effects T ELAPREVIR (I NCIVEK ) HEPATITIS C: TREATMENT

Hepatitis web study Source: Telaprevir (Incivek) Prescribing Information and Vertex Pharmaceuticals. Telaprevir (Incivek) Adverse Effects HEPATITIS C: TREATMENT

Hepatitis web study Hepatitis web study Telaprevir (Incivek) Mild Skin Rash HEPATITIS C: TREATMENT Source: Photograph Courtesy of John Scott, MD, University of Washington

Hepatitis web 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

Hepatitis web 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.

Hepatitis web study Hepatitis web study Telaprevir (Incivek) Moderate Skin Rash HEPATITIS C: TREATMENT Source: Photograph Courtesy of John Scott, MD, University of Washington

Hepatitis web 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

Hepatitis web study Hepatitis web study Telaprevir (Incivek) Severe Skin Rash HEPATITIS C: TREATMENT Source: Photograph Courtesy of John Scott, MD, University of Washington

Hepatitis web 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

Hepatitis web 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 ulcerations OR - 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.

Hepatitis web study Hepatitis web study Drug Interactions T ELAPREVIR (I NCIVEK ) HEPATITIS C: TREATMENT

Hepatitis web study Source: Vertex Pharmaceuticals. Telaprevir (Incivek) Drug-Drug Interactions: Contraindicated Medications HEPATITIS C: TREATMENT

Hepatitis web study Hepatitis web study Resistance T ELAPREVIR (I NCIVEK ) HEPATITIS C: TREATMENT

Hepatitis web 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:

Hepatitis web study Telaprevir for Chronic HCV Infection Resistance 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.

Hepatitis web study Telaprevir for Chronic HCV Infection Resistance 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.

Hepatitis web study Source: Sarrazin C, Zeuzem S. Gastroenterology. 2010;138: Telaprevir and Boceprevir Genotypic Resistance HEPATITIS C: TREATMENT MutationTelaprevirBoceprevir 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 +

Hepatitis web study Hepatitis web study Treatment Data T ELAPREVIR (I NCIVEK ) HEPATITIS C: TREATMENT

Hepatitis web study Hepatitis web 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 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

Hepatitis web study Hepatitis web study Telaprevir in Treatment Naive PROVE1 HEPATITIS C: TREATMENT

Hepatitis web study Source: McHutchison JG, et. al. N Engl J Med. 2009;360: Telaprevir for Chronic Untreated HCV Infection PROVE1: Study Design HEPATITIS C: TREATMENT Drug Dosing Telaprevir = 1250 mg on day 1, then 750 mg tid Peginterferon alfa-2a = 180 µg weekly Ribavirin = 1000 mg/d for wt 75 kg

Hepatitis web 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: Hezode C, et. al. N Engl J Med. 2009;360: McHutchinson JG, et. al. N Engl J Med. 2010;362:

Hepatitis web study PegIFN + RBV Telaprevir Source: McHutchison JG, et. al. N Engl J Med. 2009;360: Telaprevir for Chronic Untreated HCV Infection PROVE1 Study: Treatment Regimens HEPATITIS C: TREATMENT PegIFN + RBV Telaprevir PegIFN + RBV Telaprevir PegIFN T12 PR12 T12 PR24 T12 PR48 PR N=17 N=79 N=75 Week0

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection PROVE1 Study: Results Percentage of Patients with SVR Source: McHutchison JG, et. al. N Engl J Med. 2009;360: HEPATITIS C: TREATMENT T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection PROVE1 Study: Results Percentage of Patients with Relapse Source: McHutchison JG, et. al. N Engl J Med. 2009;360: HEPATITIS C: TREATMENT T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection PROVE1 Study: Results Percentage of Patients with SVR and Relapse Source: McHutchison JG, et. al. N Engl J Med. 2009;360: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Source:McHutchison JG, et. al. N Engl J Med. 2009;360: Telaprevir for Chronic Untreated HCV Infection PROVE1 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.”

Hepatitis web study Hepatitis web study Telaprevir in Treatment Naive PROVE2 HEPATITIS C: TREATMENT

Hepatitis web study Source: Hézode C, et al. N Engl J Med. 2009;360: Telaprevir for Chronic Untreated HCV Infection PROVE2: Study Design HEPATITIS C: TREATMENT Drug Dosing Telaprevir = 1250 mg on day 1, then 750 mg tid Peginterferon alfa-2a = 180 µg weekly Ribavirin = 1000 mg/d for wt 75 kg

Hepatitis web study PegIFN + RBV Telaprevir Source: Hézode C, et al. N Engl J Med. 2009;360: Telaprevir for Chronic Untreated HCV Infection PROVE2 Study: Treatment Regimens HEPATITIS C: TREATMENT PegIFN + RBV Telaprevir PegIFN + RBV Telaprevir PegIFN T12 PR12 T12 PR24 T12 P12 PR N=82 N=81 N=78 N=82 Week0

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection PROVE2 Study: Results Percentage of Patients with SVR Source: Hézode C, et al. N Engl J Med. 2009;360: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection PROVE2 Study: Results Percentage of Patients with Relapse Source: Hézode C, et al. N Engl J Med. 2009;360: HEPATITIS C: TREATMENT T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection PROVE2 Study: Results Percentage of Patients with SVR and Relapse Source: Hézode C, et al. N Engl J Med. 2009;360: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection PROVE2 Study: Results Serious Adverse Events Source: Hézode C, et al. N Engl J Med. 2009;360: HEPATITIS C: TREATMENT T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Source: Hézode C, et al. N Engl J Med. 2009;360: Telaprevir for Chronic Untreated HCV Infection PROVE2 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.”

Hepatitis web study Hepatitis web study Telaprevir in Treatment Naive ADVANCE HEPATITIS C: TREATMENT

Hepatitis web study Source: Jacobson IM, et. al. N Engl J Med. 2011;364: Telaprevir for Chronic Untreated HCV Infection ADVANCE: Study Design HEPATITIS C: TREATMENT Drug Dosing Telaprevir = 750 mg tid Peginterferon alfa-2a = 180 µg weekly Ribavirin = 1000 mg/d for wt 75 kg

Hepatitis web study Source: Jacobson IM, et. al. N Engl J Med. 2011;364: Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Treatment Regimens HEPATITIS C: TREATMENT Week 0 Telaprevir + PegIFN + RBV Placebo + PegIFN + RBV Telaprevir + PegIFN + RBV PegIFN + RBV 12 eRVR: PegIFN+ RBV No eRVR: PegIFN + RBV T8 PR 24 or 48 T12 PR 24 or 48 PR48 N =364 N =363 N =361 PegIFN + RBV eRVR: PegIFN + RBV No eRVR: PegIFN + RBV

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Results Percentage of Patients with SVR Source: Jacobson IM, et. al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: RVR and eRVR Rates Percentage of Patients with RVR and eRVR Source: Jacobson IM, et. al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT T = Telaprevir; PR = Peginterferon + Ribavirin; RVR = rapid virologic response; eRVR = extended rapid virologic response

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Results According to eRVR Percentage of Patients with SVR Source: Jacobson IM, et. al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT T = Telaprevir; PR= Peginterferon + Ribavirin; SVR = Sustained Virologic Response eRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Results According to eRVR Percentage of Patients with SVR Source: Jacobson IM, et. al. N Engl J Med. 2011;364: 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)

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Results According to Race Percentage of Patients with SVR Source: Jacobson IM, et. al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Results According to Baseline HCV RNA Percentage of Patients with SVR Source: Jacobson IM, et. al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE 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

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Adverse Effects Adverse Effects: Anemia Source: Jacobson IM, et. al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ADVANCE Study: Adverse Effects Percentage of Patients with Rash Source: Jacobson IM, et. al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Source: Telaprevir (Incivek) Prescribing Information. Vertex Pharmaceuticals. Telaprevir in Treatment-Naïve Subjects (ADVANCE) SVR Rates by IL28B rs Genotype HEPATITIS C: TREATMENT PR48 = Peginteron/Ribavirin x 48 weeks PR/T12 = Peginteron/Ribavirin + Telaprevir x 12 weeks

Hepatitis web study Source: Jacobson IM, et. al. N Engl J Med. 2011;364: Telaprevir for Chronic Untreated HCV Infection ADVANCE 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.”

Hepatitis web study Hepatitis web study Telaprevir in Treatment Naive ILLUMINATE HEPATITIS C: TREATMENT

Hepatitis web study Source: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2. Telaprevir for Chronic Untreated HCV Infection ILLUMINATE: Study Design HEPATITIS C: TREATMENT Drug Dosing Telaprevir = 750 mg tid Peginterferon alfa-2a = 180 µg weekly Ribavirin = 1000 mg/d for wt 75 kg

Hepatitis web study Source: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2. Telaprevir for Chronic Untreated HCV Infection ILLUMINATE Study: Treatment Regimens HEPATITIS C: TREATMENT 48 Week 012 Without eRVR With eRVR 2024 Telaprevir PR T12 PR 24 or 48 PR = Peginterferon + Ribavirin eRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12) eRVR (+) T12/PR24 eRVR (-) T12/PR48 eRVR (+) T12/PR48

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ILLUMINATE 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 + Ribavirin eRVR = extended rapid virologic response (undetectable HCV RNA at weeks 4 and 12)

Hepatitis web study Telaprevir for Chronic Untreated HCV Infection ILLUMINATE 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.

Hepatitis web study Source: Sherman KE, et. al. Hepatology. 2010;52 (Supplement 1):401A. Abstract LB-2. Telaprevir for Chronic Untreated HCV Infection ILLUMINATE 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 more adverse events and adverse event-related treatment discontinuations in the 48-week versus 24-week arm. These results support response-guided therapy for telaprevir-based regimens in treatment- naïve patients.”

Hepatitis web study Hepatitis web study HEPATITIS C: TREATMENT Telaprevir in Treatment Experienced PROVE3

Hepatitis web study Source: McHutchison JG, et al. N Engl J Med. 2010;362: Telaprevir for Previously Treated Chronic HCV Infection PROVE 3 Study: Study Design HEPATITIS C: TREATMENT Drug Dosing Telaprevir = 1125 mg on day 1, then 750 mg tid Peginterferon alfa-2a = 180 µg weekly Ribavirin = 1000 mg/d for wt 75 kg

Hepatitis web study Peginterferon + Ribavirin Telaprevir Source: McHutchison JG, et al. N Engl J Med. 2010;362: Telaprevir for Previously Treated Chronic HCV Infection PROVE 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= Week

Hepatitis web study Telaprevir for Previously Treated Chronic HCV Infection PROVE 3 Study: Results Percentage of Patients with SVR Source: McHutchison JG, et al. N Engl J Med. 2010;362: HEPATITIS C: TREATMENT SVR = sustained virologic response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Previously Treated Chronic HCV Infection PROVE 3 Study: Results Based on Prior History Percentage of Patients with SVR Source: McHutchison JG, et al. N Engl J Med. 2010;362: HEPATITIS C: TREATMENT SVR = sustained virologic response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Previously Treated Chronic HCV Infection PROVE 3 Study: Results Based on Prior History Percentage of Patients with SVR Source: McHutchison JG, et al. N Engl J Med. 2010;362: HEPATITIS C: TREATMENT SVR = sustained virologic response; T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Previously Treated Chronic HCV Infection PROVE 3 Study: Results Adverse Events Source: McHutchison JG, et al. N Engl J Med. 2010;362: HEPATITIS C: TREATMENT T = Telaprevir; P = Peginterferon; PR = Peginterferon + Ribavirin

Hepatitis web study Source: McHutchison JG, et al. N Engl J Med. 2010;362: Telaprevir for Previously Treated Chronic HCV Infection PROVE 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 ribavirin was more effective than retreatment with peginterferon alfa-2a and ribavirin alone.”

Hepatitis web study Hepatitis web study HEPATITIS C: TREATMENT Telaprevir in Treatment Experienced REALIZE

Hepatitis web study Source: Zeuzem S, et al. N Engl J Med. 2011;364: Telaprevir for Previously Treated Chronic HCV Infection REALIZE Study: Study Design HEPATITIS C: TREATMENT Drug Dosing Telaprevir = 750 mg q8h Peginterferon alfa-2a = 180 µg weekly Ribavirin = 1000 mg/d for wt 75 kg

Hepatitis web 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 log 10 in HCV RNA after 12 weeks of therapy Partial Response: Reduction of 2 log 10 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:

Hepatitis web study Peginterferon + Ribavirin Telaprevir Source: Zeuzem S, et al. N Engl J Med. 2011;364: Telaprevir for Previously Treated Chronic HCV Infection REALIZE: Treatment Regimens HEPATITIS C: TREATMENT Peginterferon + Ribavirin Telaprevir Peginterferon + Ribavirin T12 PR36 T12 PR48 PR48 N=266 N=264 N= Week 36416

Hepatitis web study Telaprevir for Previously Treated Chronic HCV Infection REALIZE Study: Results Percentage of Patients with SVR Source: Zeuzem S, et al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Previously Treated Chronic HCV Infection REALIZE: Results Based on Prior History Percentage of Patients with SVR Source: Zeuzem S, et al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT SVR = Sustained Virologic Response; T = Telaprevir; PR = Peginterferon + Ribavirin

Hepatitis web study Telaprevir for Previously Treated Chronic HCV Infection REALIZE: Adverse Effects Adverse Effects: Anemia Source: Zeuzem S, et al. N Engl J Med. 2011;364: HEPATITIS C: TREATMENT T = Telaprevir; P = Peginterferon + Ribavirin

Hepatitis web study Source: Zeuzem S, et al. N Engl J Med. 2011;364: Telaprevir for Previously Treated Chronic HCV Infection REALIZE 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.”

Hepatitis web study Source: Vertex Pharmaceuticals. Telaprevir in Previously Treated Subjects (REALIZE) SVR Rates by IL28B rs Genotype HEPATITIS C: TREATMENT PR48 = Peginteron/Ribavirin x 48 weeks PR/T12 = Peginteron/Ribavirin + Telaprevir x 12 weeks

Hepatitis web study Hepatitis web study Questions? HEPATITIS C: TREATMENT