HCV Advocate Video Update: Top Line Phase III Data: Boceprevir & Telaprevir

1. HCV Advocate Video Update:Top Line Phase III Data:Boceprevir & Telaprevir Alan Franciscus Executive Director, Hepatitis C Support Project Editor-in-Chief, HCV Advocate Website Join me on Twitter & Facebook – HCVAdvocate BLOG: hcvadvocate.blogspot.com/ www.hcvadvocate.org

2. Top Line Results – Boceprevir* Merck/Schering Phase III Studies: HCV Sprint 2 In HCV genotype 1 treatment- naïve patients HCV Respond 2 in HCV Genotype 1 Treatment ‘Failure’ Patients *Boceprevir (800 mg three times a day), PegIntron (1.5 mcg/kg/week) and ribavirin (600-1,400 mg day) www.hcvadvocate.org

3. HCV Sprint 2 1,097 HCV genotype 1 – treatment-naïve patients (never been treated) A 4 week lead-in treatment phase with PegIntron plus ribavirin (without boceprevir) followed by the triple combination of boceprevir, PegIntron, ribavirin www.hcvadvocate.org

4. HCV Sprint 2 Treatment was guided by treatment response 159 or 15% of the study population was African American Note: If patients were HCV RNA (viral load) positive at week 24 all treatment was stopped www.hcvadvocate.org

5. HCV Sprint 2 • Success was defined as a sustained virological response (SVR) – HCV RNA undetectable during to 24 weeks after treatment was completed • The growth factor EPO/Procrit was allowed for the treatment of anemia www.hcvadvocate.org

6. HCV Sprint 2: Study Arm & Results • Group A: • If HCV RNA (viral load) was undetectable at week 8 through week 24, treatment duration total was 28 weeks: • Results: SVR = 63% • African Americans: SVR = 42% www.hcvadvocate.org

7. HCV Sprint 2: Study Arm and Results • Group B • If HCV RNA (viral load) was positive at week 8, but undetectable at week 28, PegIntron and ribavirin were continued for a total treatment duration of 48 weeks • Results: SVR = 66% • African Americans Results: SVR = 53% www.hcvadvocate.org

8. HCV Sprint 2: Study Arm and Results • Group C • Control arm: standard of care (PegIntron, ribavirin) plus placebo (sugar pill) • Results: SVR = 38% • African Americans Results: SVR = 23% www.hcvadvocate.org

9. HCV Respond 2 403 HCV Genotype 1 Treatment “Failure” Patients A 4 week lead-in treatment phase with Pegintron plus ribavirin (without boceprevir) followed by the triple combination of boceprevir, PegIntron, ribavirin Treatment was guided by treatment response www.hcvadvocate.org

10. HCV Respond 2 • Success was defined as a sustained virological response (SVR)—HCV RNA undetectable during to 24 weeks after treatment was completed • The growth factor EPO/Procit was allowed in this study for the treatment of anemia • Note: If patients were HCV RNA POSITIVE at week 12 all treatment was stopped www.hcvadvocate.org

11. HCV Respond 2: Study Arm and Results • Group A • If HCV RNA (viral load) undetectable at week 8 and at week 12 the total treatment duration was 36 weeks • Results: SVR = 59% www.hcvadvocate.org

12. HCV Respond 2: Study Arm and Results • Group B • If HCV RNA positive at week 8, but undetectable at week 36 the combination of PegIntron plus ribavirin (without boceprevir) was continued — total treatment duration of 48 weeks • Results: SVR = 66% www.hcvadvocate.org

13. HCV Respond 2: Study Arm and Results • Group C Control arm – standard of care – combination of PegIntron, ribavirin and placebo; total treatment duration of 48 weeks • Results: SVR = 21% www.hcvadvocate.org

14. Side Effects • The side effects were similar across all study arms in both studies except: • Anemia was 20 to 27% higher in the arms that contained boceprevir • The discontinuation rate was similar between all arms. • The use of EPO/Procrit may explain the low discontinuation rate due to anemia www.hcvadvocate.org

15. Summary • The results, although top-line, are impressive and encouraging • Merck/Schering FDA filing in the US and Europe by the end of 2010 • More information at the American Association for the Study of Liver Diseases Conference—end of October, 2010 www.hcvadvocate.org

16. Top-Line Results: Telaprevir* Vertex Pharmaceuticals, INC., Phase III Study ILLUMINATE – in hcv genotype 1 treatment-naïve patients Triple combination (telaprevir, pegylated interferon, ribavirin). telaprevir was not given for more than 12 weeks www.hcvadvocate.org

17. Note: Vertex has multiple phase III studies and some of the top-line results have already been released. More complete data on various trials are expected to be released at the AASLD Conference and next year. For more information check out The HCV Advocate’s HCV Drug Pipeline www.hcvadvocate.org

18. ILLUMINATE • 540 HCV GENTOYPE 1 TREATMENT-NAÏVE PATIENTS • The aim of this study was to find out if extending the total treatment duration from 24 weeks to 48 weeks is beneficial • The use of EPO/PROCRIT was not allowed in this study www.hcvadvocate.org

19. ILLUMINATE RESULTS • When guided by treatment response: • If patients were HCV RNA negative at weeks 4 and 12, patients were randomized at week 20 into two arms: • Total treatment duration = 24 weeks • Total treatment duration = 48 weeks • Overall SVR rate was 72% www.hcvadvocate.org

20. ILLUMINATE • When patients were guided by type of response during therapy*: • SVR = 88%—24 WEEKS • SVR = 92%—48 WEEKS • The discontinuation rate (6.9%) was similar to rates seen in pegylated interferon plus ribavirin therapy * If patients were HCV RNA undetectable at weeks 4 and 12 www.hcvadvocate.org

21. ILLUMINATE • Study conclusion: Treatment duration of 24 weeks is as effective as 48 weeks • Top-line data from the REALIZE study – retreatment of prior null response and those who failed to achieve an SVR with a previous course of HCV therapy expected 9/2010 • More data on various studies is expected to be released at AASLD Conference at the end of October, 2010 www.hcvadvocate.org