SMV 150 mg QD + SOF 400 mg QD Randomisation 1 : 1 18-70 years HCV genotype 1 Naïve or pre-treated with IFN-based regimen No cirrhosis HCV RNA ≥ 10.000.

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Presentation transcript:

SMV 150 mg QD + SOF 400 mg QD Randomisation 1 : years HCV genotype 1 Naïve or pre-treated with IFN-based regimen No cirrhosis HCV RNA ≥ IU/ml No prior therapy with PI No HBV or HIV co-infection OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis 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 –SVR 12 : superiority of SMV + SOF vs historical control of approved DAA + PEG-IFN + RBV regimens (composite SVR 12 of 83% for 8 weeks and 87% for 12 weeks, with a lower limit of the 95% CI > SVR 12 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

OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis 8 weeks N = weeks N = 155 Median age, years56 Female34%37% Race : white / black77% / 20%81% / 15% Body mass index Genotype 1a Q80K+ 1a Q80K- 1b 32% 43% 25% 30% 45% 25% IL28B non-CC genotype74%72% HCV RNA log 10 IU/ml, median Prior treatment with IFN-based regimen, N (%) Relapse Non-response IFN-intolerant Other 52 (34%) (26%) Discontinued treatment, N2 (1 lost to follow-up, 1 non-compliance) Baseline characteristics and patient disposition OPTIMIST-1 Kwo P. EASL 2015, Abs LP14

SVR 12 (HCV RNA < 25 IU/ml), % (95% CI), intent-to-treat *Not superior to historical control ** Superior to historical control 8 weeks12 weeks * ( ) 97** ( ) % OverallNaïveGenotype 1a Q80K+ Experienced Genotype 1a Q80K- Genotype 1b N OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis OPTIMIST-1 Kwo P. EASL 2015, Abs LP14

SVR 12 (HCV RNA < 25 IU/ml), %, intent-to-treat OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis No impact of race, ethnicity, BMI on SVR OPTIMIST-1 Kwo P. EASL 2015, Abs LP CCTTCT < 4M≥ 4 M IL28B genotypeBaseline HCV RNA (IU/ml) % 0 8 weeks12 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 + D I170T ; I170T) –Resistance to SOF (S282T) in 1/25 relapses in the 8-week arm 8 weeks N = weeks N = 155 On-treatment virologic failure00 Relapse, N (%) Naïve patients Experienced-patients Genotype 1a Genotype 1b IL28B CC IL28B CT IL28B TT 27 (17%) 15% 23% 21% 8% 7% 16% 36% 4 (3%) 2% 5% 3% 0% 2% 8% OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis OPTIMIST-1 Kwo P. EASL 2015, Abs LP14

OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis SMV + SOF 8 weeks (N = 155) SMV + SOF 12 weeks (N = 155) Any adverse event97 (63)103 (66) Grade 3 adverse event3 (2) Grade 4 adverse event01 (1) a Serious adverse event3 (2)1 (1) AE with fatal outcome00 AE leading to discontinuation00 AE in ≥ 10% in either group Nausea Headache Fatigue 14 (9) 26 (17) 23 (15) 22 (14) 19 (12) AEs of interest Increased bilirubin Rash (any type) Pruritus (any type) Photosensitivity Dyspnea 1 (1) 12 (8) 9 (6) 5 (3) 1 (1) 10 (6) 7 (5) 2 (1) 3 (2) Adverse events, N (%) OPTIMIST-1 Kwo P. EASL 2015, Abs LP14

OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis Laboratory abnormalities, N (%) SMV + SOF 8 weeks (N = 155) SMV + SOF 12 weeks (N = 155) Increase in bilirubin Grade 1/2 Grade 3 Grade 4 21 (14) 0 21 (14) 0 Decrease in hemoglobin Grade 1/2 Grade 3 Grade 4 1 (1) Increase in amylase Grade 1/2 Grade 3 Grade 4 19 (12) 2 (1) 0 19 (12) 7 (5) 0 Increase in lipase Grade 1/2 Grade 3 Grade 4 12 (8) 2 (1) 0 14 (9) 1 (1) 0 OPTIMIST-1 Kwo P. EASL 2015, Abs LP14

 Summary –In HCV genotype 1-infected treatment-naïve and treatment-experienced patients without cirrhosis, 12 weeks of SMV + SOF led to SVR 12 rates of 97% overall, and demonstrated superiority over the historical control 8 weeks of SMV + SOF led to SVR 12 rates of 83% overall, and did not achieve superiority compared with the historical control –In the 12-week arm, SVR 12 ≥ 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 SVR 12 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 SVR 12 time point in both treatment arms OPTIMIST-1 Study: SMV + SOF for genotype 1 and no cirrhosis OPTIMIST-1 Kwo P. EASL 2015, Abs LP14