SMV 150 + SOF 400 Open-label OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis W12  Objective –Superiority of SVR 12 (HCV RNA historical control.

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Presentation transcript:

SMV SOF 400 Open-label OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis W12  Objective –Superiority of SVR 12 (HCV RNA historical control SVR 12. Analyses by ITT Lawitz E. EASL 2015, Abs LP04 N = 103 SVR 12 * Liver biopsy or Fibroscan > 12.5 kPa or Fibrotest > APRI > 2 OPTIMIST-2  Design years HCV genotype 1 Naïve or pre-treated with IFN-based regimen Non-decompensated cirrhosis* HCV RNA ≥ 10,000 IU/ml No prior therapy with PI No HBV or HIV co-infection

OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis N = 103 Median age, years58 Female19% Race : white/black80% / 18% Body mass index28.8 Genotype 1a Q80K+ 1a Q80K- 1b 33% 37% 30% IL28B non-CC genotype72% HCV RNA log 10 IU/ml, median6.8 Fibroscan score > 20 kPa15/26 (58%) Prior treatment with IFN-based regimen, n (%) Relapse Non-response IFN-intolerant Other 52 (51%) Baseline characteristics and patient disposition OPTIMIST-2 Lawitz E. EASL 2015, Abs LP04

SVR 12 (HCV RNA < 25 IU/ml), % (95% CI), intent-to-treat OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis OPTIMIST-2 Lawitz E. EASL 2015, Abs LP * ( ) *Superior to historical control 88 (78-98) OverallNaïve1a Q80K+ Experienced 79 (67-91) a Q80K- 1b N Genotype CC CTTT IL28B > ≤ 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 failure3 Relapse, N (%) Naïve patients Experienced-patients Fibroscan > 12.5 to ≤ 20 kPa Fibroscan > 20 kPa 13 (13%) 6% 19% 0% 14% OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis OPTIMIST-2 Lawitz E. EASL 2015, Abs LP04

OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis N = 103 Grade 3 adverse event5 Grade 4 adverse event1 Serious adverse event5 Adverse event with fatal outcome1 (road traffic accident) AE leading to discontinuation3 (sepsis ; rash, death by road accident) AE in ≥ 10% in either group Headache Fatigue Nausea AEs of interest Rash (any type) Pruritus Photosensitivity Dyspnea Increased bilirubin Grade 3 amylase elevation / Grade 4 lipase6 / 1 Adverse events OPTIMIST-2 Lawitz E. EASL 2015, Abs LP04

 Summary –The combination of SMV + SOF for 12 weeks demonstrated superiority in SVR 12 rates (83%) versus the historical control (70%) in treatment-naïve and -experienced HCV genotype- 1 infected patients with cirrhosis achieved SVR 12 rates higher for genotype 1a without Q80K (92%) versus those with Q80K (74%) –SVR 12 was ≥ 85% for patients with IL28B CC or CT, for treatment-naïve patients and for patients with platelet count ≥ 90,000/mm 3 –SVR 12 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 SVR 12 assessment –SMV + SOF for 12 weeks was safe and well tolerated; most adverse events were Grade 1 or 2 OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis OPTIMIST-2 Lawitz E. EASL 2015, Abs LP04