F/C AETC FacultyHIV/HCV

Thursday May 8, 2014 | 1:30- 2:30pm (EDT)

Facilitator/ PresenterDushyantha T. Jayaweera, MD, MRCOG (UK), FACP

University of Miami

Case DiscussantPatrick Marsh, MD

University of South Florida

Maribel Gonzalez, RN, ARNPUniversity of South Florida

HIV Case Conference:Highlights from EASL

Dushyantha T. Jayaweera MD, MRCOG (UK), FACP

Associate Vice Provost for Human Subject Research & Professor of Medicine, University of Miami, Miller School of Medicine, Division of Infectious DiseasesFaculty Member, Florida/Caribbean AIDS Education and Training Center

HCV TREATMENT IN TREATMENT NAIVE PATIENTS

SAPPHIRE-I Study: Design

0 12 24

ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bid ABT-333 bid + RBV bid

(n=473)(n=473)

ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bid ABT-333 bid + RBV bid

(n=473)(n=473)

Placebo*Placebo*(n=158)(n=158)

Placebo*Placebo*(n=158)(n=158)

Week

ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bidABT-333 bid + RBV bid

(n=158)(n=158)

ABT-450/r/ABT-267 qd +ABT-450/r/ABT-267 qd +ABT-333 bid + RBV bidABT-333 bid + RBV bid

(n=158)(n=158)

Double-Blind

Open-Label

Feld J, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O60.

Phase 3 StudyDouble-Blind

Key eligibility criteria•HCV genotype 1•Treatment-naïve•No cirrhosis •No HIV or HBV

SAPPHIRE-1 Study: Interim Results

• Virologic relapse: 1.7%

• 3D regimen + RBV was well-tolerated

• Discontinuations due to adverse events: 0.6%

• Most commonly reported adverse events

• Fatigue

• Headache

• Nausea

Feld J, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O60.

0

20

40

60

80

100

Pat

ien

ts

(Per

cen

tag

e)

SVR12 Rates3D Regimen + RBV

1a(n=322)

1b(n=151)

Overall(n=473)

95%98%96%

Genotype

0 12 24

ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV bid

(n=210)

ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV bid

(n=210)

ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV Placebo

(n=209)

ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV Placebo

(n=209)

Week

Phase 3 StudyDouble-Blind

Placebo-controlled

Key eligibility criteria•HCV genotype 1•Treatment-naïve•No cirrhosis •No HIV or HBV

PEARL-III Study: Design

Ferenci P, et al. 49th EASL; London, England; April 9-13, 2014. Abst. P1299.

Pearl-III Study: SVR12 and Virologic Failure Rates

3D Regimen + RBV

Ferenci P, et al. 49th EASL; London, England; April 9-13, 2014. Abst. P1299.

0

20

40

60

80

100

Pat

ien

ts (

Per

cen

tag

e)

No RBV(n=209)

With RBV(n=210)

99%99%

SVR12

0%No RBV(n=209)

0.5%With RBV

(n=210)

Virologic Failure

Pearl-III Study: Safety Results

• 3D regimen + RBV was well tolerated• Discontinuations due to adverse events

• With RBV: 0%• No RBV: 0%

• Most commonly reported adverse events• Headache• Fatigue

Ferenci P, et al. 49th EASL; London, England; April 9-13, 2014. Abst.

P1299.

ION-1 Study: Design

• GT 1 HCV treatment-naïve patients in Europe and USA• Broad inclusion criteria

• Targeted 20% enrollment of patients with cirrhosis• No upper age or BMI limit• Platelet count ≥50,000/mm3, no neutrophil minimum

• 865 patients randomized 1:1:1:1 across four arms • Stratified by HCV subtype (1a or 1b) and cirrhosis

Mangia A, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O164.

Wk 0 Wk 12 Wk 36Wk 24

LDV/SOF LDV/SOF SVR12

LDV/SOF + RBV LDV/SOF + RBV

LDV/SOF LDV/SOF

LDV/SOF + RBV LDV/SOF + RBV

SVR12

SVR12

SVR12

99 97 98 9994 100 94 100

179/180 32/34 178/184 33/33 181/184 31/33 179/181 36/36

12 Weeks 24 Weeks

LDV/SOF + RBV LDV/SOF + RBVLDV/SOF LDV/SOF

SV

R12

(P

erc

en

tag

e)

Absence of Cirrhosis Cirrhosis

ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis

Error bars represent 95% confidence intervals.

Mangia A, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O164.

179/180 32/34 178/184 33/33 181/184 31/33 179/181 36/36

12 Weeks 24 Weeks

LDV/SOF + RBV LDV/SOF + RBVLDV/SOF LDV/SOF

SV

R12

(P

erc

en

tag

e)

Absence of Cirrhosis Cirrhosis

ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis

Error bars represent 95% confidence intervals.

Mangia A, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O164.

ION-3 Study: Design

• GT 1 treatment-naïve patients without cirrhosis• Broad inclusion criteria

• No upper age or BMI limit• Opiate substitution therapy allowed

• 647 patients randomized 1:1:1 across three arms• Stratified by HCV subtype (1a or 1b)

LDV/SOF LDV/SOF

LDV/SOF LDV/SOF

LDV/SOF + RBV LDV/SOF + RBV

SVR12

SVR12

SVR12

Kowdley K, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O56.

Wk 0 Wk 12 Wk 36Wk 24

Error bars represent 95% confidence intervals.

Kowdley K, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O56.

ION-3 Study Results – Non-Inferiority Comparison

201/216202/215 206/216

p=0.52

8 Weeks 12 Weeks

LDV/SOF + RBVLDV/SOF LDV/SOF

SV

R12

(P

erc

en

tag

e)

Study Design: MK-5172 (100 mg QD) + MK-8742 (50 mg QD) ± RBV in 253 Pte

n = 31Follow-up

Follow-up

Follow-up

Follow-up

D1 TW12 SVR12TW4 TW8

TN

+ C

irrh

osi

sn

=12

3T

N +

Cir

rho

sis

n=

123

PR

-Nu

lls ±

Cir

rho

sis

n=

130

PR

-Nu

lls ±

Cir

rho

sis

n=

130

SVR24TW18 FU8FU4

Follow-up

Follow-up

Follow-up

No RBVNo RBV

+ RBV+ RBV+ RBV+ RBV

No RBVNo RBV

+ RBV+ RBV+ RBV+ RBV

+ RBV+ RBV+ RBV+ RBV

No RBVNo RBVNo RBVNo RBV

No RBVNo RBVNo RBVNo RBV

+ RBV+ RBV+ RBV+ RBV Follow-up

n = 29

n = 32

n = 31

n = 32

n = 33

n = 33

n = 32

Lawitz E, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O61.

No RBVNo RBV

+ RBV+ RBV+ RBV+ RBV

No RBVNo RBV

+ RBV+ RBV+ RBV+ RBV

+ RBV+ RBV+ RBV+ RBV

No RBVNo RBVNo RBVNo RBV

No RBVNo RBVNo RBVNo RBV

+ RBV+ RBV+ RBV+ RBV

2831

2831

32 32

2929

3031

3131

31 32

2929

2831

2930*

30 31*

2829

TW4 TW12 FU4/8

Breakthrough

Relapse

Discontinuation

Efficacy of MK-5172 + MK-8742 ± RBVin Treat-Naïve Pte + Cirrhosis:12W vs18W

• *Excludes patients who have not yet reached the FU4 time point• 12 week arms include 97% of FU8 results

Lawitz E, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O61.

Discussion