Future Directions in HCV Therapy Eric Lawitz, MD, AGAF,CPI Medical Director, The Texas Liver...

Future Directions in HCV Therapy

Eric Lawitz, MD, AGAF,CPI

Medical Director, The Texas Liver Institute

Clinical Professor of Medicine

University of Texas Health Science Center

San Antonio, Texas

IFN 6m IFN 12m IFN/RBV 6m IFN/RBV 12 m Peg-IFN 12m Peg-IFN/RBV 12m Peg-IFN/RBV/DAA0

20

40

60

80

100

SV

R (

%)

20011998

2011

StandardInterferon

+ Ribavirin

Peginterferon

1991

+ DAAs

Milestones in Therapy of CHC:Average SVR Rates from Clinical Trials

Adapted from US Food and Drug Administration, Antiviral Drugs Advisory Committee Meeting, April 27-28, 2011, Silver Spring MD.

6%

16%

34%42% 39%

55%

70+%

Generic Name Trade Name Manufacturer

BoceprevirTelaprevir

Victrelis™Incivek™

Merck Pharmaceuticals, IncVertex Pharmaceuticals, Inc

DAAs with an Indication for the Treatment of G1 Chronic Hepatitis C

• Both compounds act by inhibiting HCV nonstructural NS3/4A protease and are referred to as direct acting antivirals (DAAs)

US Food and Drug Administration. Available at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

Limitations of Current Therapy

• Telaprevir and boceprevir only approved for Genotype 1

• Interferon backbone required

• TID dosing for telaprevir/boceprevir

• Response guided therapy (both) and lead-in (boceprevir) complicated

• 24-48 week treatment

• Limited efficacy in difficult to cure patients (e.g., patients with cirrhosis, prior null responders, African-Americans)

• Hematologic (both) and rash/dermatological (telaprevir) adverse events

• Drug-drug interactions

Sofosbuvir (SOF) (GS-7977)

• NS5B nucleotide polymerase inhibitor

• Favorable administration profile

– Once daily, no food effect

– No drug-drug interactions

Completed Phase 3 Trials

• NEUTRINO

– GT 1, 4, 5, 6; treatment naïve

– No comparator

• FISSION

– GT 2 and 3; treatment naïve

– Compared to 24 weeks of peginterferon + ribavirin

• POSITRON

– GT 2 and 3; patients ineligible for or intolerant of interferon therapy

– Compared to placebo

• FUSION

– GT 2 and 3; patients unresponsive to prior treatment

– Compared to 16 weeks of sofosbuvir + ribavirin

E. Lawitz et al, Abstract 1411. EASL, April 2013; Lawitz et al., N Engl J Med 2013, 368: 1878-1887.

NEUTRINO

• Patients– GT 1, 4, 5, 6 treatment naive

– 17% compensated cirrhosis

– 17% black

– 29% IL28B genotype CC

• Regimen for all patients– Sofosbuvir 400 mg qd

– Ribavirin 1000/1200 mg qd

– Peginterferon alfa-2a 180 mcg weekly

SVR12Sofosbuvir/PEG/RBV, n=327

Week 0 12 24

NEUTRINO: Study Design

• Open label– SOF+PEG+RBV for 12 weeks (no response-guided therapy)

• Expanded inclusion criteria– No upper limit to age or BMI

– Opiate replacement therapy permitted

– Platelets ≥90,000/mm3, neutrophils ≥1,500/mm3 or

1,000/mm3 (blacks)


Series10

20

40

60

80

100 9199 99 90

Post-treatment On treatment

299/327 321/325 326/327

Week 2 Week 4 Week 12 Week 12

295/327

>90% Of Patients Have Undetectable Virus After 2 Weeks and Achieve SVR


n = 292 n = 28 n = 7

NEUTRINO: SVR by Genotype

All Patients 1 4 5, 60

20

40

60

80

10090 89

96100

Genotype

SV

R12

(%

)

295/327 261/292 27/28 7/7


n = 273 n = 54 n = 54n = 95

NEUTRINO: SVR by Subgroup

Series10

20

40

60

80

10092

98

8780

87

SV

R12

(%

)

n = 232n = 273 n = 54 n = 54

No cirrhosis Cirrhosis CC CT/TT

IL28B genotype

Black

n = 95 n = 232


Conclusions

• 12 weeks of SOF+PEG+RBV achieved 90% SVR in treatment naïve patients with GT 1, 4, 5, or 6

• 99% of patients had HCV RNA < LLOQ by treatment week 4 and all virologic failures were due to relapse

• This regimen was well tolerated


FUSION (TE)

POSITRON (Intolerant)

Week 0 12 24 36

SOF + RBV, n=256 SVR12

Peg-IFN + RBV (SOC), n=243 SVR12


Placebo, n=71 SVR12

Week 0 12 24

SOF + RBV, n=103 Placebo SVR12


Week 0 12 16 24 28

RBV does 1000-1200 mg/day for SOF + RBV and 800 mg/day for Peg-IFN + RBV.

SOF dose 400 mg once daily; RBV dose 1000-1200 mg/day.

SOF dose 400 mg once daily; RBV dose 1000-1200 mg/day.

Jacobson et al. N Engl J Med 2013, 368: 1867-1877, Lawitz et al., N Engl J Med 2013, 368: 1878-1887,

GT2 and GT 3: Study DesignsFISSION (TN)

P

<0.001

Overall GT 2 GT 30

20406080

100

SOF + RBV 12 weeks

SOF + RBV 16 weeks

P

<0.001FUSION (TE)


Overall GT 2 GT 30

20406080

100

SOF + RBV 12 Weeks

Peg-IFN + RBV 24 Weeks

Overall GT 2 GT 30

20406080

100

SV

R1

2 (

%)

SV

R1

2 (

%)

SV

R1

2 (

%)

67 67

9778

5663

170/253

162/243

68/70

52/67

102/183

110/176

50/100

69/95

31/36

30/32 19/64

39/63

5073

86 94

30

62

161/207 101/109 60/98

7893

61

SOF + RBV 12 weeks


GT2 and GT 3: SVR by GenotypeFISSION (TN)

FUSION (TE)


No cirrhosis Cirrhosis No cirrhosis Cirrhosis0

20

40

60

80

100

SOF + RBV 12 Weeks

Peg-IFN + RBV 24 Weeks

No Cirrhosis Cirrhosis0

20

40

60

80

100

GT 2 GT 30

20

40

60

80

100

No cirrhosis

Cirrhosis

SV

R1

2 (

%)

SV

R1

2 (

%)

SV

R1

2 (

%)

98 82 91

6234 30

58/59

44/54

25/26

96 100

6078

85/92 67/84

92 9468

21

16/17

6171

10/11 8/1

3

89/145

99/139 13/38 11/37

GT 2 GT 3

23/23 6/10 7/9

GT 2

No Cirrhosis Cirrhosis0

20

40

60

80

100

SOF + RBV 12 weeks

SOF + RBV 16 weeks

14/38

3763

19

61

25/40 5/26

14/23

GT 3

3/14

SVR: Patients with Cirrhosisvs No Cirrhosis


FISSION (TN)

• 12 weeks of SOF+RBV results in SVR>90% in GT 2 treatment naive patients with and without cirrhosis

• SVR rates were lower in GT 2 treatment experienced patients with cirrhosis compared to non-cirrhosis

• SOF+RBV led to similar results as PEG+RBV for GT 3 treatment naïve patients – Lowest rates observed in patients with cirrhosis

• SOF+RBV for 12 weeks is suboptimal for GT 3 treatment experienced patients– 16 weeks total duration significantly increased SVR rates

• SOF+RBV well tolerated with fewer adverse events than PEG+RBV

• Genotype 3 ≠ genotype 2 HCV– Strategies to improve GT 3 results are needed

Conclusions

Simeprevir (TMC 435) (PI)

• NS3/4A protease inhibitor

• Antiviral activity against GT 1, 2, 4, 5 and 6

• One capsule, once per day

Simeprevir (TMC 435)

Completed Phase 3 Studies

• QUEST-1 and QUEST-2

– Same study design but studies conducted independent of one another

– Treatment naïve GT 1 patients

• PROMISE

– Same study design as QUEST-1 and QUEST-2

– GT 1 prior relapsers

SMV 150 mg/PEG/RBV

PEG/RBVPEG/RBV

Post-Therapy Follow-Up Post-Therapy Follow-Up

Response Guided Treatment

Placebo/PEG/RBV

PEG/RBV PEG/RBV Post-Therapy Follow-Up

0 12 24 48 72Weeks

• Response Guided Therapy: if HCV RNA <25 IU/mL at Week 4

and undetectable at Week 12, complete treatment at Week 24

– 85-93% of patients met the criteria and qualified for total treatment

duration of 24 weeks.

QUEST-1, QUEST-2 andPROMISE Study Designs

QUEST-1 QUEST-2 PROMISE0

20

40

60

80

100 Simeprevir/PEG/RBV PEG/RBV

SV

R12

(%

)

210/264

65/130

209/257

67/134

206/260

49/133

80%

Simeprevir + PEG/RBV Achieved SVR in ~80% of Treatment Naïve and Prior Relapsers

50%

81%

50%

79%

37%

QUEST-1: SVR by Subgroup

F0-F2 F3-F4 1a 1b/other CC CT TT0

20

40

60

80

100

120

83

70 71

90 94

7665

60

28

49 52

78

42

24

SIM + PR PR

Pat

ien

ts A

chie

vin

g S

VR

12 (

%)

Fibrosis

152/183

I. Jacobson et al, Abstract 1425. EASL, April 2013

Genotype IL28B genotype

54/90

54/77

11/40

105/147

36/74

105/117

29/56

72/77

29/37

114/150

32/76

24/37

4/17

Series10

20

40

60

80

100

84.6

66.7 64.7

51 52.9

40

Simeprevir/PEG/RBV PEG/RBV

Pat

ien

ts A

chie

vin

g S

VR

12 (

%)

F0-F2 F3 F4 (Cirrhosis)

Similar results seen in QUEST-1 and PROMISE studies

SVR Higher When Simeprevir Added to PEG/RBV For Patients With All Stages

of Fibrosis/Cirrhosis (QUEST-2)

165/195

52/102

24/36

9/17

11/17

6/15

Conclusions

• Simeprevir 150 mg + PEG/RBV was highly effective against GT 1 treatment naïve patients with SVR (80%)

• Most patients (85%) receiving simeprevir were able to shorten therapy to 24 weeks

• Simeprevir 150 mg + PEG/RBV was generally well tolerated

– Rates of anemia and rash were similar in the simeprevir and placebo groups

I. Jacobson et al, Abstract 1425. EASL, April 2013

Simeprevir (TMC 435) (PI) + Sofosbuvir (GS-7977) (nuc)

Arm 1

Arm 2

Arm 3

Arm 4

Weeks

0 12 24 36 48

SMV + SOF + RBV

SMV + SOF + RBV

SMV + SOF

SMV+SOF

Post-treatment follow-up



n = 24

n = 15

n = 27

n = 14

Interim analysis SVR4 Primary endpoint SVR12


• Cohort 1: n=80 patients randomized 2:1:2:1

• Cohort 2: n=87 patients randomized 2:1:2:1

• SMV 150 mg QD + SOF 400 mg QD with/without RBV (Copegus®) 1000 or 1200 mg/day (BID)

• Interim analysis of Cohort 1 conducted when all patients in 12 week treatment arms (arms 3 and 4) reached SVR4 time point or discontinued early

COSMOS: Study Design

Lawitz et al., CROI, March 2013

• Chronic HCV GT 1 infection

• 78% GT 1a

• Prior null response to PEG/RBV

‒ Failure to achieve >2 log10 decline in HCV RNA by Week 12

• Fibrosis

• F0-F1: 41%

• F2: 59%

• IL28B

• CT: 70%

• TT: 24%

• 29% African-American

COSMOS: Key Eligibility Criteria –Cohort 1


COSMOS: Virologic Response (12 Week Arms)

0

20

40

60

80

100

85.2

10096.3 96.3

57.1

10092.9 92.9

SMV+SOF+RBV SMV+SOF

RVR, n/N (%) Undetectable end of treatment, n/N (%)

SVR4, n/N (%) SVR8, n/N (%)

23/27

8/14

27/27

14/14

26/27

13/14

26/27

13/14


SV

R8

(%)

Patients

24 weeks 12 weeks

SMV + SOF+ RBV

SMV + SOF SMV + SOF + RBV

SMV + SOF Total

(n=24) (n=15) (n=27) (n=14) (n=80)

AEs during treatment, % 87.5 93.3 88.9 78.6 87.5Grade 3/4 AEs1, % 4.2 13.3 18.5 0 10.0Serious AEs, % 0 0 0 0 0

Most common AEs (≥10% of total patients)

Fatigue, % 25.0 26.7 18.5 21.4 22.5

Headache, % 16.7 26.7 14.8 28.6 20.0

Insomnia, % 16.7 13.3 18.5 21.4 17.5

Nausea, % 4.2 6.7 18.5 28.6 13.8

Anemia, % 25.0 0 11.1 0 11.3

Cough, % 20.8 6.7 3.7 7.1 10.0

Rash, % 12.5 13.3 11.1 0 10.0

Treatment discontinuationDue to AEs, n 1 1 0 0 2Non-safety reason, n 2 1 0 0 3

RBV dose reduction, % 16.7 NA 3.7 NA 9.8

COSMOS: Safety & Tolerability

1WHO Toxicity Grading Scale, 2003


COSMOS: Cohort 2

• SMV+SOF+RBV for 12 weeks• GT 1 treatment naive and prior null

responders with advanced disease (F3/F4)• SVR4 results

– SMV+SOF+RBV: 96% (26/27)– SMV+SOF: 100% (14/14)

Medivir/Janssen Press Release, August 29, 2013

COSMOS: Summary

• 12 weeks of SMV+SOF led to an SVR8 rate

of 96% with RBV and 93% without RBV in

prior null responders with F0-F2 disease

• 12 weeks of SMV+SOF led to an SVR4 rate

of 96% with RBV and 100% without RBV in

treatment naïve and prior null responders

with F3-F4 disease

• SMV+SOF+RBV was generally well

tolerated

Daclatasvir (NS5A inhibitor) +

Sofosbuvir (GS-7977) (nuc)

Background • Patients who experience virologic failure on telaprevir or

boceprevir-based regimens currently have no treatment options

• DCV plus SOF with or without RBV achieved SVR4 in 98% of 126 HCV GT 1-infected treatment-naive patients (Sulkowski et al. AASLD 2012)

• Study Aim

– To evaluate the efficacy and safety of DCV+SOF with or without RBV for 24 weeks in GT 1-infected patients who failed prior treatment with TVR or BOC + PEG/RBV

M.S. Sulkowski et al, Abstract 1417. EASL, April 2013

Study Design

• Patients– GT 1, non-cirrhotic– Prior nonresponse, relapse, or breakthrough

during treatment with PEG/RBV+TVR or BOC– Patients who discontinued TVR or BOC due

to an AE were excluded

Week 24

Prior TVR/BOC Failures, GT 1a/1b(N = 41)

n = 21

Follow-upn = 20

DCV 60 mg QD + SOF 400 mg QD

DCV 60 mg QD + SOF 400 mg QD + RBV

Follow-up

SVR4

SVR12


Virologic Response

• 1 patient missing at post-treatment (PT) Week 12: HCV RNA was

undetectable at PT Week 4 and at PT Week 24

• 21/41 patients have reached PT Week 24; all have achieved SVR24

0

20

40

60

80

100

EOT

HC

V R

NA

< L

LO

Q

(% p

atie

nts

)

Week 2 SVR4

N =

Week 4

21 20

SVR12

21 20

21 20

21 20

21 20

DCV + SOF

DCV + SOF + RBV

Missing


Conclusions


• The all-oral, once-daily combination of DCV+SOF with or without RBV achieved SVR in all GT 1 infected patients (n=41) who failed prior treatment with TVR or BOC+PEG/RBV

• DCV+SOF with or without RBV waswell tolerated

• No Grade 3 or 4 hepatic or hematologic abnormalities

Daclatasvir (BMS-790062) (NS5A inhibitor) +

Asunaprevir (BMS-650032) (PI)

Study AI447-011 Expansion Cohort:Prior Null Responders to PEG/RBV

A. Lok, et al; APASL 2013.

A1 (DUAL): DCV 60 mg QD +ASV 200 mg BID (GT 1b only)

A2 (DUAL): DCV 60 mg QD +ASV 200 mg QD (GT 1b only)

B1 (QUAD): DCV 60 mg QD + ASV 200 mg BID + PEG/RBV (GT 1a/1b)

B2 (QUAD): DCV 60 mg QD + ASV 200 mg QD + PEG/RBV (GT 1a/1b)

B3 (TRIPLE): DCV 60 mg QD + ASV 200 mg BID + RBV (GT 1a/1b)

Follow-up

Follow-up

Follow-up

Follow-up

Follow-up

N = 21

N = 22

N = 20

N = 20

N = 18

Week 12 SVR4 SVR24

Week 24 SVR12 primary endpoint SVR48

0 4 8 12 16 20 24 PT4012345678

GT 1a patients, n=18

Weeks

HC

V R

NA

, lo

g1

0 IU

/mL

TRIPLE Therapy (Arm B3): GT 1a vs GT 1bIndividual HCV RNA Levels

• 1/18 GT 1a patient completed triple therapy and achieved SVR4

0 4 8 12 16 20 24 PT4012345678

GT 1b patients, n=4

WeeksH

CV

RN

A, l

og

10

IU/m

L

DCV + ASV 200 mg BID + RBVGraphs truncated at viral breakthrough

LLOQLOD

LLOQLOD

Conclusions

• In non-cirrhotic prior null responders,24 weeks of daclatasvir + asunaprevir appears to be an efficacious combination for GT 1b but not GT 1a

Daclatasvir (BMS-790062) (NS5A inhibitor) +

Asunaprevir (BMS-650032) (PI) +

BMS-791325 (non-nuc)

AI443-014: Study Design

• Treatment naïve non-cirrhotic patients• GT 1a: 74% and CT/TT: 70%

G. Everson et al, Abstract 1423. EASL, April 2013

Summary

The all oral, IFN-free, RBV-free, ritonavir-free combination of DCV, ASV, and BMS-791325• Achieved >90% (61/66) SVR4 and SVR12

(30/32)

• Had infrequent virologic failure (4.5%, 3/66)

• Most common AEs (≥10% total) were headache, asthenia, and gastrointestinal

G. Everson et al, Abstract 1423. EASL, April 2013

Faldaprevir (BI 201335) (PI)

Faldaprevir: Phase 3 Studies (IFN-Containing)

• STARTVerso 1– Treatment naïve GT 1 patients

– All patients from Europe and Japan

– Only Phase 3 study with results reported as of October 2013

• STARTVerso 2– Treatment naïve GT 1 patients

– Studying shorter durations (12 vs 24 weeks)

• STARTVerso 3– Treatment experienced GT 1 patients

• STARTVerso 4– Treatment naïve/prior relapsers who are coinfected with HCV

and HIV

STARTVerso1

• Phase III, randomized, double-blind, placebo-controlled trial • Patients

– Treatment naïve GT 1 infection– 78% Caucasian, 20% Asian– 39% IL28B CC– 66% GT 1b

• Regimen– PEG+RBV for 24 weeks plus faldaprevir/placebo

• Patients with early treatment success stopped all treatment atWeek 24

• Patients without Early Treatment Success and those in control arm received PEG/RBV for 48 weeks

P. Ferenci et al, Abstract 1416. EASL, April 2013

PEG/RBVPBO/PEG/RBV Observation Period

Day 1 Week 12 Week 24 Week 48 Week 72

FDV 240 mg/PEG/RBV

Observation Period

PBO/ PEG/RBV

PEG/RBV Observation Period

ETS

No ETS

Observation Period

FDV 120 mg/ PEG/RBV

PEG/RBV Observation Period

ETS

No ETS FDV 120 mg/PEG/RBV

PBO/ PEG/RBV

STARTVerso1: Study Design

• Criteria for response guided therapy

– Early Treatment Success (ETS): HCV RNA <25 IU/mL at Week 4 and

undetectable at Week 12, complete treatment at Week 24

– 88% met the criteria and qualified for total treatment duration of 24 weeks.


STARTVerso1 SVR12 rates

PEG/RBV FDV 120 + PR FDV 240 + PR0

20

40

60

80

100

52

79 80

SV

R12

(%

)

69132

204259

210261


Series10

20

40

60

80

100

80%

56%

83%

40%SV

R (

%)

195/243 204/246 9/16 6/15

No Cirrhosis Cirrhosis

FDV 120 mg/PEG/RBV

FDV 120 mg/PEG/RBV

FDV 240 mg/PEG/RBV

FDV 240 mg/PEG/RBV

SVR in Patients With Cirrhosis


0

20

40

60

80

100

SV

R12

(%

) 60%

69%76%

36%

84% 83%

60/87 143/17168/90 142/17116/45 52/86

FDV 240 mg/PEG/RBV

FDV 120 mg/PEG/RBV

PEG/RBVFDV 240 mg/PEG/RBV

FDV 120 mg/PEG/RBV

PEG/RBV

SVR By GT 1 Subtype


GT1a GT1b

STARTVerso1 Conclusions

• FDV+PEG/RBV significantly increased SVR12 rates in

GT 1 patients compared with PEG/RBV

• In total, 88% of patients treated with FDV were eligible to

stop all treatment at Week 24

• Patients without cirrhosis had higher SVR than patients

with cirrhosis

• GT 1b infected patients had higher SVR than GT 1a

infected patients

• FDV+PEG/RBV was well tolerated


Faldaprevir (BI 201335) (PI) + Deleobuvir (non nuc)

SOUND-C2: IFN-Free

– Faldaprevir + deleobuvir + RBV– SVR rates between 59-69% in GT 1 treatment

naïve patients with 16, 28 or 40 weeks of treatment

• Higher SVR in GT 1b (56-85%) vs GT 1a (38-47%)• High rate of relapse (41%) in GT 1a treated for 16

weeks

– Arm with no RBV had low SVR (39%)

Zeuzem et al., N Engl J Med 2013, 369; 630-639.

Faldaprevir: IFN-Free(Results Are Anticipated in 2014)

• HCVerso 1 (NCT01732796) and HCVerso 2

(NCT01728324)– Faldaprevir + deleobuvir + RBV

– GT 1b only

– Includes IFN-ineligible patients as well as patients with cirrhosis

– Duration of therapy: 16 vs 24 weeks

– Anticipated primary results: 1H 2014

• Study with PPI-668 (NS5A inhibitor)(NCT01859962)– Faldaprevir + deleobuvir + PPI-668 + RBV – GT 1a– Treatment naïve– Anticipated primary results: 1H 2014

ABT-450/r (PI with ritonavir), ABT-267 (NS5A inhibitor) and ABT-333

(non nuc)

AVIATOR

• Phase 2b, randomized, open-label, multicenter study

• Patients– GT 1 (66% GT 1a)– Treatment-naive and prior null response– Non-cirrhotic

• Duration– 8, 12 and 24 weeks

K.V. Kowdley et al, Abstract 3. EASL, April 2013

SVR12 (%)

SVR24(%)

VBT/Relapse

89 88 0/10

85 83 1/4

91 89 1/8

90 87 1/5

99 96 0/1

93 90 0/2

SVR12 (%)

SVR24(%)

VBT/Relapse

89 89 0/5

93 93 3/0

98 95 1/0

N Regimen/duration SVR12 (%)

SVR24**(%)

VBT/Relapse

80 ABT450 ABT267 ABT333 RBV 89 88 0/10

41 ABT450 ABT333 RBV 85 83 1/4

79 ABT450 ABT267 RBV 91 89 1/8

79 ABT450 ABT267 ABT333 90 87 1/5

79 ABT450 ABT267 ABT333 RBV 99 96 0/1

80 ABT450 ABT267 ABT333 RBV 93 90 0/2

N Regimen/duration SVR12 (%)

SVR24(%)

VBT/Relapse

45 ABT450 ABT267 RBV 89 89 0/5

45 ABT450 ABT267 ABT333 RBV 93 93 3/0

43 ABT450 ABT267 ABT333 RBV 98 95 1/0

Week 8 12 24

Trea

tmen

t n

aive

Nu

ll r

esp

on

se

** 8 patients who achieved SVR12 did not return >24 weeks and were counted as virological failures for SVR243 patients relapsed between SVR12 and SVR24

AVIATOR: Study Design


Series10

20

40

60

80

10092 91 89

94 959498

94 91 89

% w

ith

SV

R2

4

SVR24 by Baseline Subgroups – Treatment-Naïve Patients*

*Includes patients randomized to the quad therapy arms (12 or 24 weeks duration).

Mal

e

Fem

ale 1a 1b

≥7 lo

g

<7

log

F0-

F1

F2-

F3

Non

-CC

CC

N= 78 81 108 50 35 124 113 42 115 44


Series10

20

40

60

80

100 93 93 9195 9497 97 96 95

100

% w

ith

SV

R2

4

SVR24 by Baseline Subgroups – Null Responders*

*Includes patients randomized to the quad therapy arms (12 or 24 weeks duration).

Mal

e

Fem

ale 1a 1b

≥7 lo

g

<7

log

F0-

F1

F2-

F3

Non

-CC

CC

N= 55 33 55 33 22 66 41 45 85 3


Event, %Total

(N=247)Treatment-Naïve

(N=159)Null Responders

(N=88)

Headache 31.2 31.4 30.7

Fatigue 29.6 32.7 23.9

Nausea 22.7 24.5 19.3

Insomnia 19.8 22.6 14.8

Diarrhea 15.0 13.2 18.2

*Includes patients randomized to the quad therapy arms (12 or 24 weeks duration)


Most Common Adverse Events*

Safety

• 6 patients (2.4%) discontinued due to study drug-related AEs; 4 of 6 considered related to treatment.

• 4 patients (1.6%) experienced SAEs

– 1 (arthralgia) was possibly study drug-related

• Moderate-to-severe study drug-related AEs with >10% incidence in any arm were asthenia and fatigue.

• 6 patients (2.8%) and 1 patient (0.6%) experienced Grade 3-4 laboratory abnormalities in total bilirubin and ALT, respectively; all resolved with continued dosing.


AVIATOR Conclusions

• Comparable SVR12 and 24 seen with 12 and 24 weeks of treatment

• SVR rates >90% were achieved in naiveand prior null responders with a3-DAA+RBV regimen

– No clinically meaningful differences were observedby gender, HCV subtype, IL28B genotype, baselineHCV-RNA or severity of fibrosis.


Overall Summary

• All oral therapy expected to be available for GT2 and GT3 by early 2014.

• All oral therapy for GT 1 will be available no sooner than 2H2014.

• Even with PEG/RBV backbone, soon to be available DAAs for GT 1 offer advantages over currently approved DAAs.

Future Directions in HCV Therapy Eric Lawitz, MD, AGAF,CPI Medical Director, The Texas Liver...

Documents

Transcript of Future Directions in HCV Therapy Eric Lawitz, MD, AGAF,CPI Medical Director, The Texas Liver...