Interferon-Free, Oral DAA Therapy for HCV Infection therapy for HCV Infection . ... • Clemizole...

Ronald D’Amico, DO, MSc

10th Annual Health Disparities Summit April 22, 2013

Interferon-free, oral DAA therapy for HCV Infection

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/BMS791325

• SOUND-C2

Presentation Title | Date xx.xx.xx | Company Confidential © 2012 2

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: 556-62; Wiley et al, Am J Gastroenterol 2002;97:700-706;Pearlman et al. CID 2006; 42:82-91

Rates of HCV Seroprevalence among African Americans and White Populations

Pearlman B L Clin Infect Dis. 2006;42:82-91

Cirrhosis

Liver failure HCC Death

Acute infection

Chronic infection

Viral clearance

~80%

~20%

~20%

Stable or slowly progressive

Natural History of HCV Infection

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; 57:771-76

What is the effect of race on treatment outcomes?

African Americans with lower SVR rates compared to Caucasians with IFN-based therapy

Conjeevaram H et al,Gastroenterology 2006; 131:470-477; Muir A NEJM 2004; 350:22:2265

Host genetics and responsiveness to interferon-containing therapy

Favorable genetic change near IFN gene (IL-28bCC): predictive of response - regardless of race

Ge et al, Nature 2009

Why do African Americans have lower treatment responses to interferon?

Ge et al, Nature 2009

Low prevalence of favorable

genotype (IL-28b-CC)

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

Higher SVR rates with PI based triple therapy compared to dual therapy among blacks

P/R/BOC24

...but still lower response rates compared to non-black

cohort

...and optimal responses require a longer duration of

therapy in AAs

Poordad NEJM 2011; 364:1196

FDA approved in 2011 Boceprevir Telaprevir

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

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

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

Life Cycle of HCV (+ Strand, Enveloped RNA Virus)

HCV NS3 protease inhibitors

HCV NS5B polymerase inhibitors

Moradpour, D., Penin, F., & Rice, C.M. 2007. Replication of hepatitis C virus. Nature Reviews Microbiology 5: 453-463.

HCV NS5A 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

Characteristics of HCV DAA Classes

Characteristic Protease

Inhibitors

Nucleos(t)ide

Polymerase

Inhibitors

Nonnucleoside

Polymerase

Inhibitors

NS5A

Inhibitors

Potency High; variable among HCV genotypes

Moderate-high; consistent across genotype, subtype

Variable; variable among HCV genotypes

High; multiple HCV

genotypes

Barrier to

resistance

Low 1a < 1b

High 1a = 1b

Very low 1a < 1b

Low 1a < 1b

Drug interaction

potential

High Low Variable Low to moderate

Toxicity

Rash; anemia; bilirubin

Mitochondrial; nuc interactions

(ART)

Variable

Variable

Pharmacokinetics Variable; QD to TID

QD Variable; QD to TID

QD

Comments 2nd-generation PIs: better barrier,

pangenotypic

Single target; good tolerability in agents progressing in PhIII

Many targets

Multiple antiviral MOA

Direct Acting Antivirals (DAA) for HCV Infection

Protease inhibitors

• Telaprevir • Boceprevir • Simeprevir • Faldaprevir (BI-201335) • Vaniprevir • Narlaprevir • Danoprevir • GS-9256 • BMS-650032 • ACH-1625 • VX-500 • BIT-225 • ABT-450

NS5A inhibitors • daclatasvir

• BMS-824383

• PPI-461

• GS-5885

• ABT-267

Entry inhibitors • ITX-5061

NS4B inhibitors • Clemizole

Polymerase inhibitors • sofosbuvir

• Filibuvir

• ANA-598

• BI-207127

• BMS-791325

• GS-9190

• RG7129

• VX-222

• VX-759

• VX-916

• TMC-649128

• MK-3281

• IDX-375

• ABT-072

• ABT-333

• cyclophilin inhibitor • Alisporivir

• miR-122 as target • Miravirsen

. Data to be discussed

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-co-infected)

• Will overall treatment “effectiveness” improve?

Co-Pilot Study Phase 2a

Presentation Title | Date xx.xx.xx | Company Confidential © 2012 21 21 21

ABT-450/r ABT-333 RBV Cohort 1 Treatment-naïve

ABT-450/r ABT-333 RBV Cohort 2 Treatment-naïve

ABT-450/r ABT-333 RBV Cohort 3 Prior P/R non-responders

*Enrollment was limited to patients with the IL28B SNP rs12979860 CC genotype

ABT-333 400mg BID; RBV weight-based 1000-1200 mg daily dose divided BID Patients followed through 48 weeks post-treatment

250/100

150/100

150/100

19

14

17

Co-pilot Study Design

Poordad F, et al NEJM 2013; 368: 45-53

ABT-450/r 250/100 mg + ABT-333 + RBV

Treatment-naïve (n=19)

ABT-450/r 150/100 mg + ABT-333 + RBV

Treatment-naïve (n=14)

ABT-450/r 150/100 mg + ABT-333 + RBV

Treatment-experienced (n=17)

Sust

ain

ed V

iro

logi

c R

esp

on

se (

SVR

12)

rate

s CO-PILOT: SVR12 rates in treatment-naive and experienced patients on ABT-450/r plus ABT-333 plus Ribavirin

100

RBV=Ribavirin SVR= Sustained Virologic Response

23

Conclusions:

23

Among treatment-naïve HCV genotype 1 patients:

• There were no virologic breakthroughs on treatment

• SVR12 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 SVR12

• 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

Aviator Study Phase 2b

M11-652 Study Design Tr

eatm

ent-n

aïve

N

ull

Res

pond

er

ABT-450/r Dose (QD)

ABT-450 ABT-333 RBV

ABT-450 ABT-267 ABT-333 RBV


ABT-450 ABT-267 ABT-333

ABT-450 ABT-267 RBV

ABT-450 ABT-267 RBV



N

ABT-267 25mg QD; ABT-333 400mg BID; RBV weight-based 1000-1200 mg daily dose divided BID All patients to be followed through 48 weeks post-treatment


Wk 0 Wk 8 Wk 12 Wk 24

80

79

79

79

80

41

45

45 43

Regimen/Duration

150/100

150/100

100/100,200/100

150/100

100/100,150/100

100/100,150/100

200/100

100/100,150/100

100/100,150/100

SVR12 Rates (ITT) in the AVIATOR Study

88 8591 89

9989

93

0

20

40

60

80

100

26

Perc

en

tage

of

pat

ien

ts (

ITT)

ac

hie

vin

g SV

R1

2

Treatment-naϊve patients Null Responders

8 weeks 12 weeks 12 weeks

N=80 N=41 N=79 N=79 N=79 N=45 N=45

ABT-450/r ABT-267

RBV

ABT-450/r ABT-267 ABT-333


RBV

ABT-450/r

ABT-333 RBV


RBV


RBV

ABT-450/r ABT-267

RBV

Adapted from King M et al, CROI 2013 Presentation

Response Rates Treatment-naïve Patients Null Responders

Duration 8 wks 12 wks 12 wks

Regimen

450/r 267 333 RBV

450/r

333 RBV

450/r 267

RBV

450/r 267 333

450/r 267 333 RBV

450/r 267

RBV

450/r 267 333 RBV

Number dosed 80 41 79 79 79 45 45 Breakthroughs (N) 0 1 1 1 0 0 3 Relapses (N) 9 3 5 5 1 5 0 Lost to follow-up or

withdrawn consent prior

to SVR12

1 2 2 4 1 0 0

SVR12 rate (ITT)a, % (n/N)

88% (70/80)

85% (35/41)

91% (72/79)

89% (70/79)

99% (78/79)

89% (40/45)

93% (42/45)

SVR12 rate (Observed

data)b,

% (n/N)

89% (70/79)

88% (35/40)

92% (71/77)

93% (69/74)

99% (77/78)

89% (40/45)

93% (42/45)

aITT: Intent-to-treat population, includes all patients who received at least one dose of study drug bObserved data: Excludes patients with values missing for reasons other than virologic failure or discontinuation due to AEs

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

Electron Study Phase 2b

Overall Study Design in HCV GT 1,2 3: ELECTRON

n=10

n=10

n=11

n=10

GS-7977 + RBV n=10

GS-7977 + RBV n=25

GS-7977 + RBV n=25

n=9

Treatment-Naïve GT 2/3 Patients

Wk 4

GS-7977 + RBV GS-7977 + RBV

GS-7977 + P/R

Wk 8

GS-7977

GS-7977 + RBV GS-7977 + P/R

GS-7977 + RBV

Treatment-Naïve GT 2/3

Null Responders GT 1

Treatment-Naïve GT 1

Treatment-Experienced GT 2/3

n=10 GS-7977 + P/R

Wk 0 Wk 12

100% SVR24

100% SVR24

100% SVR24

100% SVR24

60% SVR24

100% SVR24

10% SVR12

84% SVR12

68% SVR12

Gane EJ, et al. AASLD 2012. Abstract 229

ELECTRON: Sofosbuvir ± GS-5885 + 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:

SVDF

Sofosbuvir + RBV 1000/1200 mg (GT1; naive) (n = 25)

Sofosbuvir + RBV 1000/1200 mg (GT1; null responders) (n = 10)

Sofosbuvir + GS-5885 + RBV 1000/1200 mg (GT1; naive) (n = 25)

Sofosbuvir + GS-5885 + 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 2012. Abstract 229; SVR12 results for SOF+5885 arm reported in Feb2013 press release

Wk 12

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 2012. Abstract 229; Gane EJ et al. CROI 2013; Abstract 41LB

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 2012. Abstract 229; Gane EJ et al. CROI 2013; Abstract 41LB

Spare Study Phase 2

GS-7977 + 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

Day 0

GS-7977 400mg daily + ribavirin 1000-1200mg (RBV)

Week 24

Part 1 n=10

n=25

Day 0

GS-7977 400mg daily + RBV1000-1200mg daily

GS-7977 400mg daily + RBV 600mg

Week 24

n=25 Part 2

Osinusi et al. AASLD 2012; LB4

Efficacy Results

90% 96% 96%

88%

72%

56%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Full dose RBV Full dose RBV Low dose RBV

Part 1 Part 2

HC

V R

NA

<LL

OQ

(%

pat

ien

ts)

Treatment Response (ITT Patients)

Week 4

Week 12

ETR

SVR4

SVR12


No serious adverse events (AE) or discontinuations due to AEs

No grade 4 events; Two Grade 3 events of nausea and hyperbilirubinemia

Safety Results

Grade 2 Adverse Events n(%)

GS-7977 + Full dose RBV n=35

GS-7977 + 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)


• 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%).

Conclusions


Daclatasvir and Sofosbuvir with or without RBV Phase 2

All-Oral Combination of Daclatasvir (NS5A Inhibitor) + Sofosbuvir (NS5B Inhibitor), +/- RBV in Treatment-Naïve Patients Chronically Infected With HCV Genotype 1, 2, or 3

SOF 400 mg QD x 7 days, then add DCV 60 mg QD Follow-up N=15 A

DCV 60 mg QD + SOF 400 mg QD

Follow-up N=14 C DCV 60 mg QD

+ SOF 400 mg QD + RBV Follow-up N=15 E DCV 60 mg QD + SOF 400 mg QD

Follow-up N=41 G DCV 60 mg QD +

SOF 400 mg QD + RBV Follow-up N=41 H

SOF 400 mg QD x 7 days, then add DCV 60 mg QD

Follow-up N=16 B DCV 60 mg QD

+ SOF 400 mg QD Follow-up N=14 D

DCV 60 mg QD + SOF 400 mg QD + RBV Follow-up N=14 F

GT 2/3

GT 1 a/b

Wk 12 Wk 24 SVR48

SVR48

Treatment Naïve, Non-

Cirrhotic Patients

Sulkowski M, et al. AASLD 2012; LB2

Study Design

Efficacy Results

100% 100% 100%

98%

95%

88%

100%

86%

93% 93%

75%

80%

85%

90%

95%

100%

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

GT 1a/b GT 2/3

HC

V R

NA

<LL

OQ

(%

Pat

ien

ts)

Virologic Response After Treatment

SVR4

SVR12

SVR24

LI= Lead In


No grade 3 or 4 elevations of ALT, AST, and bilirubin

Safety Results

Patients with event, n (%)

24-week Treatment 12-week Treatment A and B

SOF LI + DCV

N=31

C and D DCV + SOF

N=28

E and F DCV + SOF + RBV

N=29

G DCV + SOF

N=41

H DCV + SOF + RBV

N=41

Safety Parameters

Grade 3-4 AEs 0 4 (14) 2 (7) 1 (2) 1 (2) Discontinuations due to AEs 0 1 (4) 1 (3) 0 0

SAEs 2 (6) 4 (14) 2 (7) 1 (2) 0 Hgb <9 g/dL (grade 3-4) 0 0 6 (21) 0 5 (12)

Adverse Events occuring in ≥ 20% of patients total

Fatigue 9 (29) 14 (50) 9 (31) 16 (39) 13 (32) Headache 5 (16) 8 (29) 11 (38) 14 (34) 9 (22) Nausea 5 (16) 9 (32) 9 (31) 8 (20) 8 (20)


• 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.

Conclusions

Daclatasvir and Asunaprevir + BMS-791325 without RBV Phase 2a

Phase 2a, Safety and Tolerability Study; Part 2 is ongoing.

Treatment-naïve HCV GT1 infected, non-cirrhotic subjects

45

An Interferon-free, Ribavirin-free 12-Week Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS-791325 (NS5B inhibitor) in Treatment-Naïve Patients with Genotype (GT) 1 Chronic Hepatitis C Virus (HCV) Infection

ASV 200mg BID + DCV 60mg QD+ BMS-791325 75mg BID

Follow-up

Follow-up Group 1 n=16

Group 2 n=16

ASV 200mg BID + DCV 60mg QD + BMS-791325 75mg BID

ASV 200mg BID + DCV 60mg QD+ BMS-791325 150mg

Follow-up

Follow-up Group 3

Group 4

Week 12

ASV 200mg BID + DCV 60mg QD + BMS-791325 150mg

Week 24 Day 1

Part 1

Part 2

Everson et al. AASLD 2012; LB3

No virologic breakthrough in either group

Efficacy Results

100%

94% 94% 94%

88%

100%

94%

82%

84%

86%

88%

90%

92%

94%

96%

98%

100%

4 12 EOT PT4(SVR4)

PT12(SVR12)

Pat

ien

ts A

chie

vin

g En

dp

oin

t (%

)

Study Week

HCV RNA < LLOQ (MITT Analysis)

Group 1 (24 week treatment)

Group 2 (12 week treatment)


No Grade 3/4 elevations in ALT/AST or bilirubin were observed.

Renal calculus deemed not-related to study drug.

Safety Results

Number of Patients (%) Group 1 24 Week

Treatment N=16

Group 2 12 Week

Treatment N=16

Total

N=32

Serious AEs 0 1 (5) Renal Calculus

1 (3)

AEs leading to discontinuation 0 0 0 Grade 3-4 AE 0 1 (6)

Grade 3 headache 1 (3)

Grade 3-4 laboratory abnormalities 0 1 (6) Lymphopenia

1 (3)

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)


• Twelve weeks of the interferon- and ribavirin-free regimen of DCV + ASV + BMS-791325 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.

Conclusions

Sound-C2 Study Phase 2b

IFN free combination of BI 201335 (Faldaprevir) + BI 207127 (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 non-type), compensated cirrhosis (9%)

BI 201335 120 mg QD + BI207127 600 mg TID + RBV

Follow-up

Day 1 Week 16 Week 28 Week 48

Follow-up

Follow-up

Follow-up

Follow-up

n=81

n=80

n=77

n=78

n=46

BI 201335 120 mg QD + BI 207127 600 mg TID + RBV


BI 201335 120 mg QD + BI207127 600 mg BID + RBV


Soriano et al, AASLD 2012; Abstract #84

Efficacy Results- SVR

43% 50%

0%

43% 42%

11%

57%

80%

33%

68%

86%

60%

0%10%20%30%40%50%60%70%80%90%

100%

TID16, 28, & 48

+

BID28+

TID28-

TID16, 28, & 48

+

BID28+

TID28-

SV

R (

%)

SVR12 Rates by HCV-1 Subtype

GT-1aGT-1b

Cirrhosis No Cirrhosis

BI 207127 Dosing Duration (weeks)

RBV


Efficacy Results- Failure

19%

33%

67%

21% 26%

44%

6% 0% 0%

8% 0%

10%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

TID16, 28, & 48

+

BID28+

TID28-

TID16, 28, & 48

+

BID28+

TID28-

Failu

re R

ate

(%

)

On-treatment Failure and Relapse Rates

On Treatment Failure

Relapse

BI 207127 Dosing Duration (weeks)

RBV

Cirrhosis No Cirrhosis


Safety Results

n (%)

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)

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) 0 0 0 1 (2) Photosensitivity AEs 2 (10) 4 (2) 0 0 0 0 Vomiting AEs 1 (5) 7 (3) 0 0 0 0 Asthenia 0 6 (3) 0 0 0 0 Jaundice AEs 2 (10) 2 (1) 0 0 0 0


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 207127 (BID) + RBV in compensated cirrhosis

AbbVie Phase 3 Clinical Development Program

Phase 3 program – evaluation of 3 DAA regimen in broad range of GT1 patient populations, with and without RBV

M11-646 SAPPHIRE-I (GT1 naïve, placebo controlled) N=600

M13-098 SAPPHIRE-II (GT1 exp, placebo controlled) N=400

M14-002 PEARL-IV (GT1a naive, +/- RBV) N=300

M13-961 PEARL III (GT1b naive, +/- RBV) N=400

M13-099 TURQUIOSE-II (GT1 naïve/exp, cirrhotics) N=300

M13-389 PEARL-II (GT1b exp, +/- RBV) N=200

*M14-004 TURQUOISE-I (GT1 HIV/HCV) N=300 S

peci

al

Pop

ulat

ions

R

BV-

free

3DA

A +

RB

V

* Submitted as a supplement to the NDA 3| 12-18-13 Company Confidential © 2013

Interferon-Free, Oral DAA Therapy for HCV Infection therapy for HCV Infection . ... • Clemizole...

Documents

Transcript of Interferon-Free, Oral DAA Therapy for HCV Infection therapy for HCV Infection . ... • Clemizole...