SMV + DCV + SOF Open label Chronic HCV infection Genotype 1 or 4 Treatment-naïve or pre-treated with PEG-IFN ± RBV Portal hypertension or liver decompensation.

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Presentation transcript:

SMV + DCV + SOF Open label Chronic HCV infection Genotype 1 or 4 Treatment-naïve or pre-treated with PEG-IFN ± RBV Portal hypertension or liver decompensation No hepatocellular carcinoma Total bilirubin ≤ 3 x ULN, Platelet ≥ 30,000/mm 3, Albumin ≤ 2.5 g/dl, INR ≤ 2.5, eGFR ≥ 30 ml/min No HBV or HIV co-infection SVR 12 SMV + DCV + SOF N = 21 CP A < 7 + PH CP B 7-9 N = 19 CP : Child-Pugh ; PH : portal hypertension  Design  Objective –SVR 12 (HCV RNA < 15 IU/ml) SMV 150 mg qd + DCV 90 mg qd + SOF 400 mg qd Lawitz E. AASLD 2015, Abs. 39 IMPACT IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease W12

IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease CP A, N = 19CP B, N = 21 Median age, years5661 Female26%48% Race : white / black95% / 5%100% / 0 Body mass index, mean Genotype 1a (NS3 Q80K) 1b 4 15 (9/15) (3/10) 10 0 IL28B CC genotype21%14% HCV RNA log 10 IU/ml, median Treatment-experienced47%48% Fibroscan score, kPa, median Child-Pugh score : 5 / 6 / 7 / 8 / 9, N14 / 5 / 0 / 0 / 00 / 0 / 9 / 8 / 4 MEL score < 10 / / ≥ 15, N12 / 7 / 010 / 9 / 2 Albumin, g/dl, median Platelets x 10 3 /mm 3, median Lawitz E. AASLD 2015, Abs. 39 IMPACT Baseline characteristics

IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease CP A, N = 19CP B, N = 21 SVR 12 (HCV RNA < 15 UI/ml)100% Outcome Decreased, N = 11 No change, N = 23 Increased, N = 6 Baseline CP score Decreased, N = 20 No change, N = 13 Increased, N = 7 Change in Child-Pugh score at follow-up W12Change in MELD score at follow-up W12 Lawitz E. AASLD 2015, Abs. 39 IMPACT 5–67– Baseline MELD score < 10≥ 10-< 15≥ 15

SMV, DCV and SOF pharmacokinetics following administration of SMV + DCV + SOF  Intensive PK analysis performed at Week 2 and Week 8 –Mean SMV exposure: 2.2-fold higher in CP B than CP A –Mean DCV exposure: similar in CP B and CP A –Mean SOF exposure: 1.4-fold higher in CP B than CP A –Mean GS exposure (SOF metabolite): similar in CP B and CP A Lawitz E. AASLD 2015, Abs. 39 IMPACT IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease

Adverse events and laboratory abnormalities, N (%) IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease CP A, N = 19CP B, N = 21 Serious adverse event0 1 (5) GI haemorrhage, not related Adverse event related to study drug3 (16)7 (33) Adverse event leading to discontinuation00 Death00 Adverse event in ≥ 2 patients in any group, N Pruritus12 Photosensitivity21 Nausea12 Hepatic encephalopathy02 Anemia20 Insomnia02 Total bilirubin grade 3 / grade 4, N2 / 05 / 2 Lipase grade 3 / grade 4, N0 / 11 / 0 Glucose elevations grade 3 / grade 4, N1 / 01 / 1 Lawitz E. AASLD 2015, Abs. 39 IMPACT

Lawitz E. AASLD 2015, Abs. 39 IMPACT IMPACT Study: SMV + DCV + SOF in HCV genotype 1 with decompensated liver disease  Summary –Treatment for 12 weeks with SMV, SOF, and DCV resulted in 100% response rate; all 19 Child-Pugh A patients and all 21 Child-Pugh B patients achieved SVR 12 –High virologic response was observed regardless of Child-Pugh class (<7 or 7–9) or the presence of resistance-associated variants at baseline –This 3-DAA combination was generally safe and well tolerated No discontinuations due to adverse events No deaths