10 th Annual Health Disparities Summit. Interferon-free, oral DAA therapy for HCV Infection. April 22, Ronald D Amico, DO, MSc

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1 10 th Annual Health Disparities Summit April 22, 2013 Ronald D Amico, DO, MSc Interferon-free, oral DAA therapy for HCV Infection

2 Outline Epidemiology of HCV in African Americans Protease Inhibitor based Standard of Care (SOC) Interferon free therapy PILOT/CO-PILOT AVIATOR ELECTRON and SPARE trials DCV/SOF and DCV/ASV/BMS SOUND-C2 Presentation Title Date xx.xx.xx Company Confidential

3 Epidemiology of HCV in African Americans The NHANES III survey estimated that 1.8% (3.9 million) of the U.S. population had a positive HCV antibody test with a rate significantly higher in blacks compared to whites (3.2% versus 1.5%). 74% of the 3.9 million individuals in the US had chronic infection with the rate of viremia higher in blacks compared to whites (86% versus 68%) and the rate of clearance lower. African Americans were more likely to be infected with genotype 1 virus (88%) than were non- African Americans (67%). Although HCV RNA levels were similar, liver enzymes (ALT) were lower in African Americans Black men had higher rates of infection with the highest prevalence rate (9.8%) among black males ages 40 to 49 years. After adjusting for socioeconomic status and high-risk behaviors, race was not a risk factor for HCV infection. Although the prevalence of HCV is greater in African Americans, natural history data has suggested a more favorable outcome for African Americans. African Americans had less inflammation and fibrosis in their liver biopsies, and there was a trend toward less cirrhosis (22% versus 30%). Alter et al, NEJM 1999; 341: ; Wiley et al, Am J Gastroenterol 2002;97: ;Pearlman et al. CID 2006; 42:82-91

4 Rates of HCV Seroprevalence among African Americans and White Populations Pearlman B L Clin Infect Dis. 2006;42:82-91

5 Natural History of HCV Infection Acute infection ~20% Viral clearance ~80% Chronic infection ~20% Factors associated with accelerated progression: Alcohol HIV co-infection Fatty liver Older age at infection Duration of infection Being Caucasians or Hispanic compared to African Americans Kohla M Dig Dis Sci 2012; 57: Cirrhosis Stable or slowly progressive Liver failure HCC Death

6 What is the effect of race on treatment outcomes?

7 African Americans with lower SVR rates compared to Caucasians with IFN-based therapy Conjeevaram H et al,gastroenterology 2006; 131: ; Muir A NEJM 2004; 350:22:2265

8 Host genetics and responsiveness to interferoncontaining therapy

9 Favorable genetic change near IFN gene (IL-28bCC): predictive of response - regardless of race Ge et al, Nature 2009

10 Why do African Americans have lower treatment responses to interferon? Low prevalence of favorable genotype (IL-28b-CC) Ge et al, Nature 2009

11 Do directly-acting agents on the hepatitis C virus make a difference in treatment response rates?

12 Higher SVR rates with PI based triple therapy compared to dual therapy among blacks...but still lower response rates compared to non-black cohort...and optimal responses require a longer duration of therapy in AAs FDA approved in 2011 Boceprevir Telaprevir P/R/BOC24 Poordad NEJM 2011; 364:1196

13 Adverse events associated with PEG-IFN/Ribavirin Fatigue and flu-like symptoms Loss of appetite/weight loss Thyroid abnormalities Nausea, diarrhea, headache Risk of teratogenicity with ribavirin

14 Low enrollment rates of African-Americans in clinical trials Barriers: Constitutional neutropenia seen in blacks Abnormal creatinine Uncontrolled diabetes Melia M et al. Hepatology 2011; 54:70-78

15 IFN free, all oral DAA combinations for HCV Infection Clinical Trial Results

16 Life Cycle of HCV (+ Strand, Enveloped RNA Virus) HCV NS3 protease inhibitors HCV NS5B polymerase inhibitors (a) Virus binding and internalization (liver cell) (b) Uncoating and cytoplasmic release of viral RNA (c) Protein translation and polyprotein processing (d) RNA replication (e) Packaging and assembly (f) Virion maturation and release HCV NS5A inhibitors Moradpour, D., Penin, F., & Rice, C.M Replication of hepatitis C virus. Nature Reviews Microbiology 5:

17 Characteristics of HCV DAA Classes Characteristic Potency Barrier to resistance Drug interaction potential Toxicity Pharmacokinetics Comments Protease Inhibitors High; variable among HCV genotypes Low 1a < 1b Nucleos(t)ide Polymerase Inhibitors Moderate-high; consistent across genotype, subtype High 1a = 1b Nonnucleoside Polymerase Inhibitors Variable; variable among HCV genotypes Very low 1a < 1b NS5A Inhibitors High; multiple HCV genotypes Low 1a < 1b High Low Variable Low to moderate Rash; anemia; bilirubin Variable; QD to TID 2nd-generation PIs: better barrier, pangenotypic Mitochondrial; nuc interactions (ART) QD Single target; good tolerability in agents progressing in PhIII Variable Variable; QD to TID Many targets Variable QD Multiple antiviral MOA

18 Direct Acting Antivirals (DAA) for HCV Infection Protease inhibitors Telaprevir Boceprevir Simeprevir Faldaprevir (BI ) Vaniprevir Narlaprevir Danoprevir GS-9256 BMS ACH-1625 VX-500 BIT-225 ABT-450 NS5A inhibitors daclatasvir BMS PPI-461 GS-5885 ABT-267 Entry inhibitors ITX-5061 NS4B inhibitors Clemizole Polymerase inhibitors sofosbuvir Filibuvir ANA-598 BI BMS GS-9190 RG7129 VX-222 VX-759 VX-916 TMC MK-3281 IDX-375 ABT-072 ABT-333 cyclophilin inhibitor Alisporivir mir-122 as target Miravirsen. Data to be discussed

19 Critical questions Will we be able to use oral direct-acting agents (DAAs) without interferon? Will we be able to use oral DAAs without ribavirin? Will response rates be comparable or improved in all patients, including prior null responders and those with traditionally lower SVR (eg, African-Americans)? How many DAAs will be required? Will the regimen vary for different patients? Will DAAs be effective in special populations? (eg, cirrhotics, HIV-coinfected) Will overall treatment effectiveness improve?

20 Co-Pilot Study Phase 2a

21 Co-pilot Study Design Cohort 1 Treatment-naïve 19 ABT-450/r ABT-333 RBV 250/100 Cohort 2 Treatment-naïve 14 ABT-450/r ABT-333 RBV 150/100 Cohort 3 Prior P/R nonresponders 17 ABT-450/r ABT-333 RBV 150/100 ABT mg BID; RBV weight-based mg daily dose divided BID Patients followed through 48 weeks post-treatment * Enrollment was limited to patients with the IL28B SNP rs CC genotype 2 Presentation Title Date xx.xx.xx Company Confidential

22 CO-PILOT: SVR 12 rates in treatment-naive and experienced patients on ABT-450/r plus ABT-333 plus Ribavirin 100 Sustained Virologic Response (SVR 12 ) rates ABT-450/r 250/100 mg + ABT RBV Treatment-naïve (n=19) ABT-450/r 150/100 mg + ABT RBV Treatment-naïve (n=14) ABT-450/r 150/100 mg + ABT RBV Treatment-experienced (n=17) RBV=Ribavirin SVR= Sustained Virologic Response Poordad F, et al NEJM 2013; 368: 45-53

23 Conclusions: Among treatment-naïve HCV genotype 1 patients: There were no virologic breakthroughs on treatment SVR 12 rates were 93-95% for naïve patients ABT-450/r 250/100 mg and 150/100 mg doses showed comparable response rates Among previous P/R non-responders: 47% achieved SVR 12 All patients who relapsed did so by their first post-treatment visit Relapse after PTW12 was infrequent (1/61, 1.6% of patients) The combination of ABT-450/r + a non-nucleoside inhibitor + RBV was associated with a low rate of discontinuation (1.6%) due to adverse events during 12 weeks of treatment 23

24 Aviator Study Phase 2b

25 M Study Design N Regimen/Duration ABT-450/r Dose (QD) 80 ABT-450 ABT-267 ABT-333 RBV 150/100 Treatment-naïve ABT-450 ABT-333 RBV ABT-450 ABT-267 RBV ABT-450 ABT-267 ABT-333 ABT-450 ABT-267 ABT-333 RBV ABT-450 ABT-267 ABT-333 RBV 150/ /100,200/ / /100,150/ /100,150/100 Wk 0 Wk 8 Wk 12 Wk 24 Null Responder ABT-450 ABT-267 RBV ABT-450 ABT-267 ABT-333 RBV ABT-450 ABT-267 ABT-333 RBV 200/ /100,150/ /100,150/100 ABT mg QD; ABT mg BID; RBV weight-based mg daily dose divided BID All patients to be followed through 48 weeks post-treatment

26 SVR 12 Rates (ITT) in the AVIATOR Study Percentage of patients (ITT) achieving SVR N=80 N=41 N=79 N=79 N=79 N=45 N=45 ABT-450/r ABT-267 ABT-333 RBV ABT-450/r ABT-333 RBV ABT-450/r ABT-267 RBV ABT-450/r ABT-267 ABT weeks 12 weeks 12 weeks Treatment-naϊve patients 99 ABT-450/r ABT-267 ABT-333 RBV 89 ABT-450/r ABT-267 RBV 93 ABT-450/r ABT-267 ABT-333 RBV Null Responders Adapted from King M et al, CROI 2013 Presentation 26

27 Response Rates Treatment-naïve Patients Null Responders Duration 8 wks 12 wks 12 wks Regimen 450/r RBV 450/r 333 RBV 450/r 267 RBV 450/r /r RBV 450/r 267 RBV 450/r RBV Number dosed Breakthroughs (N) Relapses (N) Lost to follow-up or withdrawn consent prior to SVR 12 SVR 12 rate (ITT) a, % (n/n) SVR 12 rate (Observed data) b, % (n/n) 88% (70/80) 89% (70/79) 85% (35/41) 88% (35/40) 91% (72/79) 92% (71/77) 89% (70/79) 93% (69/74) 99% (78/79) 99% (77/78) 89% (40/45) 89% (40/45) 93% (42/45) 93% (42/45) a ITT: Intent-to-treat population, includes all patients who received at least one dose of study drug b Observed data: Excludes patients with values missing for reasons other than virologic failure or discontinuation due to AEs

28 Conclusions: The 12-week 3 DAA + RBV regimens showed the greatest efficacy in both treatment-naïve and null responder populations SVR12 (ITT) in 99% of GT1treatment-naïve patients on three DAA/RBV and 93% of GT1-infected null responders receiving three DAA/RBV. The combination of ABT-450/r, ABT-267 and ABT-333 will be studied both with and without RBV in phase 3 trials An ABT-450/r/ABT-267 co-formulated tablet will be used in phase 3 All DAA combinations studied were well tolerated through 8-12 weeks of treatment Fatigue, headache, insomnia, and nausea were seen most frequently 1% of patients discontinued due to adverse events

29 Electron Study Phase 2b

30 Overall Study Design in HCV GT 1,2 3: ELECTRON Wk 0 Wk 4 Wk 8 Wk 12 n=10 GS RBV 100% SVR24 Treatment-Naïve GT 2/3 Patients n=9 n=10 GS P/R GS RBV GS RBV GS RBV 100% SVR24 100% SVR24 n=11 n=10 GS P/R GS % SVR24 60% SVR24 Treatment-Naïve GT 2/3 n=10 GS P/R 100% SVR24 Null Responders GT 1 n=10 GS RBV 10% SVR12 Treatment-Naïve GT 1 n=25 GS RBV 84% SVR12 Treatment-Experienced GT 2/3 n=25 GS RBV 68% SVR12 Gane EJ, et al. AASLD Abstract 229

31 ELECTRON: Sofosbuvir ± GS RBV in Naive and Previous Null Responders (GT1 Results) Pts with poor prognostic indicators: GT1a (86%), male (54%), nonwhite (12%), IL28B CT/TT (68%) Mean BMI: 26; mean HCV RNA: 6.2 log Study Design: Wk 12 Sofosbuvir + RBV 1000/1200 mg (GT1; naive) (n = 25) SVDF Sofosbuvir + RBV 1000/1200 mg (GT1; null responders) (n = 10) Sofosbuvir + GS RBV 1000/1200 mg (GT1; naive) (n = 25) Sofosbuvir + GS RBV 1000/1200 mg (GT1; nulls) (n = 9) *Data reported for 3 pts only then 9/9 Subjects SVR4 reported in Jan2013 press release Gane EJ, et al. AASLD Abstract 229; SVR12 results for SOF+5885 arm reported in Feb2013 press release

32 ELECTRON Results SOF + RBV* SOF + LDV + RBV** Naïve (n=25) Null Responder (n=10) Naïve (n=25) Null Responder (n=9) GT1a 88% 90% 80% 89% SVR 4 88% 11% 100% 100% SVR 12 21/25 (84%) 1/10 (10%) 25/25 (100%) 9/9 (100%) SAEs 1 (4%) 0 2 (8%) 9 AEs that led to DC 0 0 1(4%) 0 > Grade 2 Anemia 0 1 (10%) 5 (20%) 0 Grade 3: Urine Occult Blood** 5 (20%) 4 (40%) 13 (52%) 2 (22%) **Majority of occult blood findings unconfirmed or in females. *SAE: urethral injury unrelated to SOF LDV= Ledipasvir= GS5885 Gane EJ, et al. AASLD Abstract 229; Gane EJ et al. CROI 2013; Abstract 41LB

33 Conclusions Genotype 1 Patients 12 weeks SOF + RBV provided SVR12 in 84% of treatment-naïve patients and 10% of null responders. Addition of GS-5885 to SOF + RBV provided SVR4 and SVR12 in 100% of treatment-naïve patients and 100% of null responders Regimen is safe and well tolerated Gane EJ, et al. AASLD Abstract 229; Gane EJ et al. CROI 2013; Abstract 41LB

34 Spare Study Phase 2

35 GS Low or Full dose RBV for 24 weeks In Difficult To Treat HCV Infected Genotype 1 Patients : Interim Analysis: SPARE Trial. HCV genotype 1a/b, treatment naïve patients Part 1: Stage 0-2 fibrosis; Part 2: All stages (including Child Pugh A) Study Design Part 1 n=10 GS mg daily + ribavirin mg (RBV) Day 0 Week 24 Part 2 n=25 n=25 Day 0 GS mg daily + RBV mg daily GS mg daily + RBV 600mg Week 24 Osinusi et al. AASLD 2012; LB4

36 Efficacy Results 100% 90% 90% Treatment Response (ITT Patients) 96% 96% 88% HCV RNA <LLOQ (% patients) 80% 70% 60% 50% 40% 30% 20% 72% 56% Week 4 Week 12 ETR SVR4 SVR12 10% 0% Full dose RBV Full dose RBV Low dose RBV Part 1 Part 2 Osinusi et al. AASLD 2012; LB4

37 Safety Results No serious adverse events (AE) or discontinuations due to AEs No grade 4 events; Two Grade 3 events of nausea and hyperbilirubinemia Grade 2 Adverse Events n(%) GS Full dose RBV n=35 GS Low dose RBV n=25 Headache 0 2 (8) Nausea 1 (3) 1 (4) Fatigue 1 (3) 0 Rash 2 (6) 1 (4) Pruritus 1 (3) 1 (4) Myalgia 0 2 (8) Depression 1 (3) 0 Neutropenia 0 1 (4) Hyperbilirubinemia 4 (11) 1 (4) Decreased Hgb 7 (20) 1 (4) Osinusi et al. AASLD 2012; LB4

38 Conclusions Early viral decay was rapid and independent of RBV dosing. GS-7977 in combination with full dose RBV resulted in high efficacy rates in subjects with early fibrosis Low dose RBV with GS-7977 appears to be similarly efficacious in suppressing HCV replication in difficult to treat subjects Anemia was more common in patients receiving full dose of RBV(20% vs 4%). Osinusi et al. AASLD 2012; LB4

39 Daclatasvir and Sofosbuvir with or without RBV Phase 2

40 All-Oral Combination of Daclatasvir (NS5A Inhibitor) + Sofosbuvir (NS5B Inhibitor), +/- RBV in Treatment-Naïve Patients Chronically Infected With HCV Genotype 1, 2, or 3 Study Design Treatment Naïve, Non- Cirrhotic Patients GT 2/3 GT 1 a/b N=16 B N=14 D N=14 F N=15 A N=14 C N=15 E N=41 G N=41 H SOF 400 mg QD x 7 days, then add DCV 60 mg QD DCV 60 mg QD + SOF 400 mg QD DCV 60 mg QD + SOF 400 mg QD + RBV SOF 400 mg QD x 7 days, then add DCV 60 mg QD DCV 60 mg QD + SOF 400 mg QD DCV 60 mg QD + SOF 400 mg QD + RBV DCV 60 mg QD + SOF 400 mg QD DCV 60 mg QD + SOF 400 mg QD + RBV Follow-up Follow-up Follow-up Follow-up Follow-up Follow-up Follow-up Follow-up SVR48 Sulkowski M, et al. AASLD 2012; LB2 Wk 12 Wk 24 SVR48

41 Efficacy Results 100% 100% 100% 100% Virologic Response After Treatment 98% 100% HCV RNA <LLOQ (% Patients) 95% 90% 85% 80% 95% 93% 93% 88% 86% SVR4 SVR12 SVR24 75% A: SOF LI + DCV C: DCV + SOF E: DCV + SOF + RBV G: DCV + SOF (12 wks) H: DCV + SOF + RBV (12 wks) B: SOF LI + DCV D: DCV + SOF F: DCV + SOF + RBV LI= Lead In GT 1a/b GT 2/3 Sulkowski M, et al. AASLD 2012; LB2

42 Safety Results No grade 3 or 4 elevations of ALT, AST, and bilirubin 24-week Treatment C and D DCV + SOF 12-week Treatment A and B E and F G Patients with event, n (%) SOF LI + DCV DCV + SOF + RBV DCV + SOF N=29 N=31 N=28 N=41 Grade 3-4 AEs 0 4 (14) 2 (7) 1 (2) 1 (2) Discontinuations 0 1 (4) 1 (3) 0 0 due to AEs Safety Parameters SAEs 2 (6) 4 (14) 2 (7) 1 (2) 0 Hgb <9 g/dl (grade 3-4) H DCV + SOF + RBV N= (21) 0 5 (12) Adverse Events Fatigue 9 (29) 14 (50) 9 (31) 16 (39) 13 (32) occuring in 20% Headache 5 (16) 8 (29) 11 (38) 14 (34) 9 (22) of patients total Nausea 5 (16) 9 (32) 9 (31) 8 (20) 8 (20) Sulkowski M, et al. AASLD 2012; LB2

43 Conclusions 24 weeks of the all-oral, once-daily combination of DCV plus SOF achieved high rates of SVR (more than 93%) in previously untreated patients with HCV genotype 1, 2, or 3. IL28B genotype, genotype 1 subtype, and the use of ribavirin did not influence response. 96% of patients with HCV genotype 1 achieved SVR4 following 12-weeks treatment. After 24 -week treatment 98% of patients achieved SVR24. The most common adverse events (>20%) were fatigue, headache, and nausea.

44 Daclatasvir and Asunaprevir + BMS without RBV Phase 2a

45 An Interferon-free, Ribavirin-free 12-Week Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS (NS5B inhibitor) in Treatment-Naïve Patients with Genotype (GT) 1 Chronic Hepatitis C Virus (HCV) Infection Phase 2a, Safety and Tolerability Study; Part 2 is ongoing. Treatment-naïve HCV GT1 infected, non-cirrhotic subjects Part 1 Group 1 n=16 Group 2 n=16 ASV 200mg BID + DCV 60mg QD+ BMS mg BID ASV 200mg BID + DCV 60mg QD + BMS mg BID Follow-up Follow-up Part 2 Group 3 Group 4 ASV 200mg BID + DCV 60mg QD+ BMS mg ASV 200mg BID + DCV 60mg QD + BMS mg Follow-up Follow-up Day 1 Week 12 Week 24 Everson et al. AASLD 2012; LB3 45

46 Efficacy Results No virologic breakthrough in either group Patients Achieving Endpoint (%) 100% 98% 96% 94% 92% 90% 88% 86% 84% 82% 100% 94% 94% 94% 88% HCV RNA < LLOQ (MITT Analysis) 100% 4 12 EOT PT4 (SVR4) Study Week 94% PT12 (SVR12) Group 1 (24 week treatment) Group 2 (12 week treatment) Everson et al. AASLD 2012; LB3

47 Safety Results No Grade 3/4 elevations in ALT/AST or bilirubin were observed. Renal calculus deemed not-related to study drug. Number of Patients (%) Group 1 24 Week Treatment N=16 Group 2 12 Week Treatment N=16 Serious AEs 0 1 (5) Renal Calculus Total N=32 AEs leading to discontinuation Grade 3-4 AE 0 1 (6) 1 (3) Grade 3 headache Grade 3-4 laboratory abnormalities 0 1 (6) Lymphopenia AE in >10% of patients in combined treatment groups Headache 4 (25) 6 (38) 10 (31) Diarrhea 2 (13) 6 (38) 8 (25) Asthenia 2 (13) 3 (19) 5 (16) 1 (3) 1 (3) Everson et al. AASLD 2012; LB3

48 Conclusions Twelve weeks of the interferon- and ribavirin-free regimen of DCV + ASV + BMS was well tolerated and achieved a high rate of SVR4 in chronic HCV GT1-infected patients who were mainly GT1a and IL28B non-cc genotype. There was no viral breakthrough and no posttreatment relapse to date. Further investigation of this regimen in the treatment of HCV is warranted. Study Part 2 is ongoing.

49 Sound-C2 Study Phase 2b

50 IFN free combination of BI (Faldaprevir) + BI (NS5B inhibitor) ± ribavirin (RBV) in treatment-naïve patients with HCV GT 1 infection and compensated liver cirrhosis Open-Label Phase 2b study HCV treatment-naïve patients with GT 1a or 1b with IL28B (CC or nontype), compensated cirrhosis (9%) n=81 BI mg QD + BI mg TID + RBV Follow-up n=80 BI mg QD + BI mg TID + RBV Follow-up n=77 BI mg QD + BI mg TID + RBV Follow-up n=78 n=46 BI mg QD + BI mg TID + RBV BI mg QD + BI mg BID + RBV Follow-up Follow-up Day 1 Week 16 Week 28 Week 48 Soriano et al, AASLD 2012; Abstract #84

51 Efficacy Results- SVR SVR12 Rates by HCV-1 Subtype SVR (%) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% BI Dosing Duration (weeks) RBV 43% 57% TID 16, 28, & 48 + Cirrhosis 50% 80% BID % 33% TID 28-68% 43% 42% TID 16, 28, & 48 + No Cirrhosis 86% BID % 60% TID 28 - GT-1a GT-1b Soriano et al, AASLD 2012; Abstract #84

52 Efficacy Results- Failure On-treatment Failure and Relapse Rates Failure Rate (%) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% BI Dosing Duration (weeks) RBV 19% 6% TID 16, 28, & 48 + Cirrhosis 33% BID % 0% 0% TID 28-21% 8% TID 16, 28, & 48 + No Cirrhosis 26% BID % On Treatment Failure Relapse 44% TID 28-10% Soriano et al, AASLD 2012; Abstract #84

53 Safety Results TID16W, 28W, & 40W BID28W TID28W-NR Cirrhosis (n=21) No Cirrhosis (n=217) Cirrhosis (n=9) No Cirrhosis (n=69) Cirrhosis (n=3) No Cirrhosis (n=47) n (%) Overall AEs, n(%) 20 (95) 203 (94) 9 (100) 64 (93) 2 (67) 42 (98) Severe AEs, n(%) 3 (14) 18 (8) 1 (11) 8 (12) 1 (33) 3 (7) Serious AEs, n(%) 4 (19) 12 (6) 1 (11) 7 (10) 0 3 (7) Discontinuation due to AE, n(%) 6 (29) 27 (12) 1 (11) 5 (7) 0 5 (12) Aes at Discontinuation Rash AEs 3 (14) 4 (2) (2) Photosensitivity AEs 2 (10) 4 (2) Vomiting AEs 1 (5) 7 (3) Asthenia 0 6 (3) Jaundice AEs 2 (10) 2 (1) Soriano et al, AASLD 2012; Abstract #84

54 Conclusions Patients with cirrhosis had lower SVR rates across all dose groups compared with those without cirrhosis. High on-treatment failure rate in TID 28 week arm (67% and 44% in cirrhotic and noncirrhotic patients, respectively). The most common adverse events (AEs) in patients with cirrhosis were mild rash and gastrointestinal side effects. Phase III will evaluate 24 weeks faldaprevir + BI (BID) + RBV in compensated cirrhosis

55 AbbVie Phase 3 Clinical Development Program

56 Phase 3 program evaluation of 3 DAA regimen in broad range of GT1 patient populations, with and without RBV RBV-free 3DAA + RBV Special Populations M SAPPHIRE-I (GT1 naïve, placebo controlled) N=600 M SAPPHIRE-II (GT1 exp, placebo controlled) N=400 M PEARL-II (GT1b exp, +/- RBV) N=200 M PEARL III (GT1b naive, +/- RBV) N=400 M PEARL-IV (GT1a naive, +/- RBV) N=300 M TURQUIOSE-II (GT1 naïve/exp, cirrhotics) N=300 *M TURQUOISE-I (GT1 HIV/HCV) N=300 * Submitted as a supplement to the NDA Company Confidential 2013