treatment of hepatitis c gt 3 -...
TRANSCRIPT
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?