This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice

related to any specific patient.

Frontier AIDS Education and Training Center

Treatment of Hepatitis C GT 3

John Scott, MD, MSc

Associate Professor, Medicine

University of Washington

Dec 3, 2015

Disclosures

• I have served on the DSMB for Tacere Therapeutics,

Advisory Board for Gilead Sciences, and my institution has

received research funding from Merck.

Genotype 3BACKGROUND

Background

• 10% of all US cases

• Faster rates of fibrosis progression

• More steatosis

• Higher incidence of hepatocellular carcinoma

• SOF/RBV x 24 wks is expensive and not much better cure

rate c/w IFN/RBV (~70%)

• Least activity of SOF

• Current AASLD/IDSA recs:

- 1) PegIFN/RBV/SOF x 12 wks

- 2) SOF/DCV x 12-24 wks

Zeuzem S, Dusheiko GM, Salupere R, et al. Sofosbuvir and ribavirin in HCV

genotypes 2 and 3. N Engl J Med. 2014;370:1993-2001

All-Oral Treatment With Daclatasvir Plus

Sofosbuvir Plus Ribavirin for 12 or 16 Weeks in

HCV Genotype 3-Infected Patients With Advanced

Fibrosis or Cirrhosis: The ALLY-3+ Phase 3 Study

Leroy V1, Angus P,2 Bronowicki JP,3 Dore G,4 Hézode C,5 Pianko S,6 Pol S,7 Stuart K,8 Tse E,9 McPhee F,10 Bhore R,11

Jimenez-Exposito MJ,11 Thompson A4

1CHU de Grenoble, La Tronche, France; 2Austin Hospital, Heidelberg, Australia; 3CHU Nancy & Lorraine University, Nancy, France; 4St. Vincent’s Hospital and Kirby

Institute, Sydney, Australia; 5CHU Henri Mondor, Créteil, France; 6Monash Medical Centre, Clayton, Australia; 7Hôpital Cochin, Paris, France; 8Gallipoli Medical Research

Foundation, Greenslopes, Australia; 9Royal Adelaide Hospital, Adelaide, Australia; 10Bristol-Myers Squibb Research & Development, Wallingford, CT; 11Bristol-Myers

Squibb Research & Development, Princeton, NJ.

The Liver Meeting 2015®San Francisco, CA, 13–17 November 2015 Oral LB-3

ALLY-3+ Study Design

Baseline Demographics and Disease Characteristics

SVR12: All Treated Patients

SVR12: Patients with Cirrhosis

Resistance-associated

Variants (RAVs) at Baseline and Failure

AASLD 2015, San Francisco

Sofosbuvir/Velpatasvir Fixed-Dose Combination for 12 Weeks Compared to Sofosbuvir with Ribavirin for

24 Weeks in Genotype 3 HCV-Infected Patients: The Randomized Controlled Phase 3 ASTRAL-3

Study

Alessandra Mangia1, Stuart K. Roberts2, Stephen Pianko3, Alex Thompson4, Curtis Cooper5, Brian Conway6, Marc Bourliere7, TarikAsselah8, Thomas Berg9, Stefan Zeuzem10, William Rosenberg11, Kosh Agarwal12, Edward J. Gane13, Catherine Stedman14, Francesco Mazzotta15, Tram T. Tran16, Stuart Gordon17, Evguenia Svarovskaia18, Lingling Han18, John McNally18, Anu Osinusi18, Diana M. Brainard18, John G. McHutchison18, Nezam Afdhal19, Graham R. Foster20

1Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy; 2Alfred Health and Monash University, Prahran, Victoria, Australia; 3Monash Health and Monash University, Clayton, Victoria, Australia; 4St Vincent’s Hospital, Melbourne, Victoria, Australia; 5Ottawa

General Hospital, Ottawa, Ontario, Canada; 6Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada; 7Hôpital Saint

Joseph, Marseille, France; 8University Paris Diderot, INSERM U773, Paris, France; 9Leipzig University Hospital, Germany; 10 Johann

Wolfgang Goethe University, Frankfurt, Germany; 11University College London, UK; 12Kings College Hospital, London, UK; 13Auckland

Clinical Studies, New Zealand; 14Christchurch Clinical Studies Trust and University of Otago, Christchurch, New Zealand; 15Santa Maria

Annunziata Hospital, Florence, Italy; 16Cedars-Sinai Medical Center, Los Angeles, CA; 17Henry Ford Health System, Detroit, MI; 18Gilead

Sciences, Inc., Foster City, CA; 19Beth Israel Deaconess Medical Center, Boston, MA; 20Queen Mary University of London, UK

Study Design

ASTRAL-3

• Open-label, active-comparator trial

• Broad inclusion criteria

• 1:1 randomization to SOF/VEL or SOF + RBV

- Stratified by prior treatment (TN/TE) and cirrhosis (presence/absence)

• Conducted at 76 sites in US, Canada, UK, Germany, France, Italy, Australia,

and New Zealand

n=250

n=250

Week 0 12 24

SVR12

SVR12SOF + RBV

36

SOF/VEL

Results: Demographics

ASTRAL-3

SOF/VEL

12 Weeks

n=277

SOF + RBV

24 Weeks

n=275

Mean age, y (range) 49 (21‒76) 50 (19‒74)

Male, n (%) 170 (61) 174 (63)

White, n (%) 250 (90) 239 (87)

Mean BMI, kg/m2 (range) 26 (17‒48) 27 (17‒56)

Cirrhosis, n (%) 80 (29) 83 (30)

Treatment experienced, n (%) 71 (26) 71 (26)

IL28B CC, n (%) 105 (38) 111 (40)

HCV RNA, log10 IU/mL (range) 6.2 (3.7‒7.5) 6.3 (3.6‒7.5)

Results: Disposition

ASTRAL-3

Patients, n (%)

SOF/VEL

12 Weeks

n=277

SOF + RBV

24 Weeks

n=275

Completed drug 275 (99) 254 (92)

Discontinued 2 (<1) 21 (8)

AE 0 9 (3)

Lost to follow-up 0 4 (1)

Noncompliance 1 (<1) 2 (<1)

Withdrew consent 0 3 (1)

Death 0 2 (<1)

Lack of efficacy 1 (<1) 1 (<1)

Results: SVR12

ASTRAL-3

95

80

0

20

40

60

80

100

SV

R12 (

%)

264/277 221/275

p <0.001*

SOF/VEL

12 Weeks

SOF + RBV

24 Weeks

*p-value for superiority of SOF/VEL compared with SOF+ RBV.

Error bars represent 95% confidence intervals.

Results: SVR12 by Cirrhosis or Treatment History

ASTRAL-3

9791

9790

87

66

86

63

0

20

40

60

80

100

SOF/VEL SOF + RBV

No Yes Naïve Experienced

Cirrhosis Status Treatment History

191197

7380

5583

200206

176204

6471

4571

163187

• Error bars represent 95% confidence intervals.

SV

R12 (

%)

Results: SVR12 by Cirrhosis or Treatment History

ASTRAL-3

9791

9790

87

66

86

63

0

20

40

60

80

100

SOF/VEL SOF + RBV

No Yes Naïve Experienced

Cirrhosis Status Treatment History

191197

7380

5583

200206

176204

6471

4571

163187

• Error bars represent 95% confidence intervals.

SV

R12 (

%)

4 relapses2 other

16 relapses8 other

7 relapses 22 relapses6 other

4 relapses2 other

15 relapses13 other

7 relapses 1 non-response23 relapses2 other

Results: Resistance Analysis

ASTRAL-3: SOF/VEL Group

84%

No BL

NS5A RAVs

n=231

16% BL NS5A

RAVsn=43

Total, n=274

97%

SVR12

225/231

88%

SVR12

38/43

• SVR12 was 84% (21/25) in patients with Y93H

Summary

Regimen SVR Cost Comments

PegIFN/RBV/SO

F x 12 wks

88-95% $110-120,000 Highest SE profile

SOF/DCV x 12-

24 wks

83-92% $150-300,000 Add RBV if cirrhotic

or treat for 24 wks

SOF/VEL 90-97% ???, similar to

Harvoni?

Expected in May

2016, pan-genotypic

Treatment options for GT 3:

Questions?