smv 150 + sof 400 open-label optimist-2 study: smv + sof for genotype 1 and cirrhosis w12 objective...

SMV 150 + SOF 400

Open-label

OPTIMIST-2 Study: SMV + SOF for genotype 1and cirrhosis

W12

Objective– Superiority of SVR12 (HCV RNA < 25 IU/ml) versus a historical control (composite

of SVR with SOF + PEG-IFN + RBV in naïve and SMV + PEG-IFN + RBV in experienced patients (SVR12 of 70%) : lower limit of the 95% CI for the SVR12 > historical control SVR12. Analyses by ITT

Lawitz E. EASL 2015, Abs LP04

N = 103SVR12

* Liver biopsy or Fibroscan > 12.5 kPa or Fibrotest > 0.75 + APRI > 2

OPTIMIST-2

Design

18-70 yearsHCV genotype 1

Naïve or pre-treatedwith IFN-based regimen

Non-decompensated cirrhosis*

HCV RNA ≥ 10,000 IU/mlNo prior therapy with PI

No HBV or HIV co-infection


N = 103Median age, years 58

Female 19%

Race : white/black 80% / 18%

Body mass index 28.8

Genotype1a Q80K+1a Q80K-1b

33%37%30%

IL28B non-CC genotype 72%

HCV RNA log10 IU/ml, median 6.8

Fibroscan score > 20 kPa 15/26 (58%)

Prior treatment with IFN-based regimen, n (%)RelapseNon-responseIFN-intolerantOther

52 (51%)2

179

25

Baseline characteristics and patient disposition

OPTIMIST-2 Lawitz E. EASL 2015, Abs LP04

SVR12 (HCV RNA < 25 IU/ml), % (95% CI), intent-to-treat



25

50

100

75

83*(75.8-91.1)

*Superior to historical control

88(78-98)

Overall Naïve 1aQ80K+

Experienced

79(67-91)

74

9284

1aQ80K-

1b

N 103 50 53 34 38 310

Genotype

CC

86 8579

CT TT

29 54 19

IL28B

> 20

80

100

≤ 20

15 11

Fibroscan

%

Failures, overall and according to sub-groups, N (%)

* 7/12 had genotype 1a and prior null response to PEG-IFN + RBV

Resistance testing (population sequencing) of 14 failures– NS3 resistance emergence to SMV, N = 11 (position 168 alone or R155K

alone or combined with mutations at other positions)– Resistance to SOF (S282T) : 0

N = 103

On-treatment virologic failure 3

Relapse, N (%)Naïve patientsExperienced-patientsFibroscan > 12.5 to ≤ 20 kPa Fibroscan > 20 kPa

13 (13%)6%

19%0%

14%




N = 103

Grade 3 adverse event 5

Grade 4 adverse event 1

Serious adverse event 5

Adverse event with fatal outcome 1 (road traffic accident)

AE leading to discontinuation 3 (sepsis ; rash, death by road accident)

AE in ≥ 10% in either groupHeadacheFatigueNausea

212111

AEs of interestRash (any type)Pruritus PhotosensitivityDyspneaIncreased bilirubin

1614532

Grade 3 amylase elevation / Grade 4 lipase 6 / 1

Adverse events


Summary– The combination of SMV + SOF for 12 weeks

• demonstrated superiority in SVR12 rates (83%) versus the historical control (70%) in treatment-naïve and -experienced HCV genotype- 1 infected patients with cirrhosis

• achieved SVR12 rates higher for genotype 1a without Q80K (92%) versus those with Q80K (74%)

– SVR12 was ≥ 85% for patients with IL28B CC or CT, for treatment-naïve patients and for patients with platelet count ≥ 90,000/mm3

– SVR12 was ≥ 94% for cirrhotic patients with albumin ≥ 4 g/dl and FibroScan score >12.5 to ≤ 20 kPa

– Viral relapse was the primary reason for not achieving SVR12 – Patient-reported outcomes scores significantly improved from baseline,

as observed by the Week 12 follow-up visit coincident with the SVR12 assessment

– SMV + SOF for 12 weeks was safe and well tolerated; most adverse events were Grade 1 or 2



smv 150 + sof 400 open-label optimist-2 study: smv + sof for genotype 1 and cirrhosis w12 objective...

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