smv 150 mg qd + sof 400 mg qd randomisation 1 : 1 18-70 years hcv genotype 1 naïve or pre-treated...

SMV 150 mg QD + SOF 400 mg QD

Randomisation1 : 118-70 years

HCV genotype 1Naïve or pre-treated

with IFN-based regimenNo cirrhosis

HCV RNA ≥ 10.000 IU/mlNo prior therapy with PI

No HBV or HIV co-infection

OPTIMIST-1 Study: SMV + SOF for genotype 1and no cirrhosis

N = 155

N = 155

W12

* Randomisation was stratified on genotype (1a with Q80K or 1a without Q80K or 1b), IL28B (CC or non-CC) and prior HCV treatment history (naïve/relapse or non-response or other)

Objective– SVR12 : superiority of SMV + SOF vs historical control of approved DAA + PEG-IFN

+ RBV regimens (composite SVR12 of 83% for 8 weeks and 87% for 12 weeks, with a lower limit of the 95% CI > SVR12 of historical control). If superiority, assessment of non-inferiority of 8 vs 12 weeks of SMV + SOF. Analyses by ITT

SMV 150 mg QD + SOF 400 mg QD

W8

OPTIMIST-1

Design

Kwo P. EASL 2015, Abs LP14


8 weeksN = 155

12 weeksN = 155

Median age, years 56 56

Female 34% 37%

Race : white / black 77% / 20% 81% / 15%

Body mass index 26.9 28.0

Genotype1a Q80K+1a Q80K-1b

32%43%25%

30%45%25%

IL28B non-CC genotype 74% 72%

HCV RNA log10 IU/ml, median 6.85 6.83

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

52 (34%)13101118

40 (26%)8

142

16

Discontinued treatment, N 2 (1 lost to follow-up, 1 non-compliance)

Baseline characteristics and patient disposition

OPTIMIST-1 Kwo P. EASL 2015, Abs LP14

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

*Not superior to historical control** Superior to historical control

8 weeks 12 weeks

25

50

100

75

83*(76.3-88.9)

97**(93.7-99.9)

%

85

97

Overall Naïve Genotype 1aQ80K+

Experienced

77

95

73

96

84

9792

97

Genotype 1aQ80K-

Genotype 1b

N 155 155 103 115 52 40 49 46 67 70 39 390



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


No impact of race, ethnicity, BMI on SVR


93

100

CC TTCT

84

97

64

9296

77

97

< 4M ≥ 4 M

41 43 86 86 28 26 48 56 107 99

IL28B genotype Baseline HCV RNA (IU/ml)

25

50

100

75

%

0

8 weeks 12 weeks

96

N

Relapses, 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 28 relapses– Resistance emergence to SMV, N = 2 (R155K + D1682 + I170T ; I170T)– Resistance to SOF (S282T) in 1/25 relapses in the 8-week arm

8 weeksN = 155

12 weeksN = 155

On-treatment virologic failure 0 0

Relapse, N (%)Naïve patientsExperienced-patientsGenotype 1aGenotype 1bIL28B CCIL28B CTIL28B TT

27 (17%)15%23%21%8%7%

16%36%

4 (3%)2%5%3%3%0%2%8%




SMV + SOF 8 weeks(N = 155)

SMV + SOF 12 weeks(N = 155)

Any adverse event 97 (63) 103 (66)

Grade 3 adverse event 3 (2) 3 (2)

Grade 4 adverse event 0 1 (1)a

Serious adverse event 3 (2) 1 (1)

AE with fatal outcome 0 0

AE leading to discontinuation 0 0

AE in ≥ 10% in either groupNauseaHeadacheFatigue

14 (9)26 (17)23 (15)

23 (15)22 (14)19 (12)

AEs of interestIncreased bilirubinRash (any type)Pruritus (any type)PhotosensitivityDyspnea

1 (1)12 (8)9 (6)5 (3)1 (1)

1 (1)10 (6)7 (5)2 (1)3 (2)

Adverse events, N (%)



Laboratory abnormalities, N (%)SMV + SOF 8 weeks

(N = 155)SMV + SOF 12 weeks

(N = 155)Increase in bilirubin

Grade 1/2Grade 3Grade 4

21 (14)00

21 (14)00

Decrease in hemoglobinGrade 1/2Grade 3Grade 4

1 (1)00

000

Increase in amylaseGrade 1/2Grade 3Grade 4

19 (12)2 (1)

0

19 (12)7 (5)

0

Increase in lipaseGrade 1/2Grade 3Grade 4

12 (8)2 (1)

0

14 (9)1 (1)

0


Summary– In HCV genotype 1-infected treatment-naïve and treatment-experienced

patients without cirrhosis, 12 weeks of SMV + SOF led to SVR12 rates of 97% overall, and demonstrated superiority over the historical control

• 8 weeks of SMV + SOF led to SVR12 rates of 83% overall, and did not achieve superiority compared with the historical control

– In the 12-week arm, SVR12 ≥ 92% were observed in all subgroups, including those with baseline characteristics historically associated with a poor response to HCV treatment (non-CC IL28B genotype, high HCV RNA at baseline, genotype 1a [with or without Q80K])

– In the 8-week arm, high SVR12 rates were observed in patients with baseline HCV RNA < 4 million IU/ml (96%), genotype 1b (92%) and IL28B CC genotype (93%)

– Patients in the 8-week arm with baseline HCV RNA < 4 million IU/ml had low relapse rates (4%)

– Treatment with SMV+SOF for 12 or 8 weeks was safe and well tolerated, with no discontinuations due to adverse events

– Patient-reported symptoms and quality of life significantly improved from baseline to the SVR12 time point in both treatment arms



smv 150 mg qd + sof 400 mg qd randomisation 1 : 1 18-70 years hcv genotype 1 naïve or pre-treated...

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