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Reddy KR. Lancet Infect Dis. 2015;15:27-35 Reddy KR. Lancet Infect Dis. 2015;15:27-35

Reddy KR. Lancet Infect Dis. 2015;15:27-35 - PowerPoint Presentation

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Reddy KR. Lancet Infect Dis. 2015;15:27-35 - PPT Presentation

ATTAIN SMV TVR placebo PEGIFN RBV TVR SMV placebo PEGIFN RBV Randomisation 1 1 Doubleblind 18 years HCV genotype 1 HCV RNA 10000 IU ml Null or partial responders to ID: 168524

ifn peg attain rbv peg ifn rbv attain genotype previous smv responders tvr adverse treatment reddy telaprevir study simeprevir

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Slide1

Reddy KR. Lancet Infect Dis. 2015;15:27-35

ATTAIN

SMV + TVR placebo

+ PEG-IFN + RBV

TVR + SMV placebo + PEG-IFN + RBV

Randomisation*

1 : 1

Double-blind

≥ 18 years

HCV genotype 1HCV RNA ≥ 10,000 IU/mlNull or partial responders to previous PEG-IFN + RBVCompensated cirrhosis allowedNo HBV or HIV co-infection

ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders with genotype 1

Design

N = 384

N = 379

W12

W48

* Randomisation was stratified on genotype (1a or 1b) and previous response to PEG-IFN + RBV (partial or null)

PEG-IFN + RBV

PEG-IFN + RBV

Treatment regimens

SMV : 150 mg

qd

, or placebo ; TVR : 750 mg

tid

, 7-9h apart, or placebo

PEG-IFN

a

-2a : 180

m

g SC once weekly

RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)

Primary efficacy endpoint

Non inferiority of SMV : SVR

12

(HCV RNA < 25 IU

/ml)

by intention to treat (lower margin of the 2-sided 95% CI for the difference with TVR = 12%)Slide2

SMV

N = 379

TVR

N = 384

Median

age, years

50

52

Female

36%

42%

Genotype

1a (Q80K present /Q80K absent)

1b

Other

43% (23% / 77%)

57%

< 1%

42% (17% / 83%)

57%

1%

IL28B CC genotype

4%

5%

HCV RNA log10 IU/ml, median6.566.57Metavir fibrosis score F0-F2 / F3-F456% / 44%55% / 45%Prior treatment with PEG-IFN + RBVNull response62%62%Partial response38%38%Discontinued treatment, nAdverse eventLost to follow-upWithdrawal 2101011294619

Baseline characteristics and patient disposition

Reddy KR. Lancet Infect Dis. 2015;15:27-35

ATTAIN

ATTAIN Study:

simeprevir

versus

telaprevir

,

with PEG-IFN + RBV in previous non responders

with genotype 1Slide3

SVR

12

(HCV RNA < 25 IU

/ml)

difference : - 1.1%

(95% CI : -7.8 to 5.5)

SMV

TVR

On treatment

failure

34%

20%

Viral breaktrough

22%

20%

Relapse

17%

17%

Reddy KR. Lancet Infect Dis. 2015;15:27-35

ATTAIN

ATTAIN Study: simeprevir versus telaprevir,

with PEG-IFN + RBV in previous non responders

with genotype 1

%

SMVTVRN37914538423422014613337272152205444704427643455466840266739020406080100AllPrevious null responsePrevious

partial

response1a

Q80K-

1a Q80K+

1b

Cirrhosis

238

124

215Slide4

NS3 Sequencing

SMV

TVR

Sequencing available

148/176 failures

134/176 failures

Emerging mutations

142/148

111/134

Main mutations detected (positions)

80

122

155

168

36

54

155

156

Reddy KR. Lancet Infect Dis. 2015;15:27-35

ATTAIN

ATTAIN Study: simeprevir versus telaprevir,

with PEG-IFN + RBV in previous non responders

with genotype 1Slide5

SMV, N = 379

TVR, N = 384

AE leading to treatment discontinuation

12 (3%)

39 (10%)

Grade 3 adverse event

72 (19%)

84 (22%)

Grade 4 adverse event

14 (4%)

21 (5%)

Serious adverse event

8 (2%)

33 (9%)

Adverse event of interest

Rash (any type)

81 (21%)

119 (31%)

Pruritus

122 (32%)

170 (44%)

Photosensitivity

8 (2%)

1 (< 1%)

Neutropenia69 (18%)52 (14%)Anemia51 (13%)144 (38%)Dyspnea 27 (7%)36 (9%)Increased bilirubin30 (8%)28 (7%)Additional AE in ≥ 20% of patients in either group

Fatigue

120 (32%)

146 (38%)

Pyrexia

81 (21%)

94 (24%)

Headache

95 (25%)

111 (29%)

Nausea

64 (17%)

109 (28%)

Adverse events, N (%)

Reddy KR. Lancet Infect Dis. 2015;15:27-35

ATTAIN

ATTAIN Study: simeprevir versus telaprevir,

with PEG-IFN + RBV in previous non responders

with genotype 1Slide6

ATTAIN Study: simeprevir versus telaprevir, with PEG-IFN + RBV in previous non responders

with genotype 1

SummarySMV + PEG-IFN + RBV showed non-inferiority with regard to SVR

12 to TVR + PEG-IFN + RBV in patients with chronic HCV genotype 1 infection and compensated liver disease who were null or partial responders to previous treatment with PEG-IFN + RBV

Non-inferiority was met for null or partial responders separately as wellRates of on-treatment failure, viral breakthrough, and relapse were similar between the two treatment groupsThe incidence of adverse events deemed at least possibly related

to SMV or TVR was noticeably lower in the SMV group, and most adverse events were grade 1 or 2 Serious adverse events were infrequent and less common in the SMV group, and fewer patients needed to discontinue SMV compared with TVR because of an adverse event

Reddy KR. Lancet Infect Dis. 2015;15:27-35ATTAIN