ALLY-1  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml) in genotype 1 DCV 60 mg qd + SOF 400 mg qd + RBV DCV 60 mg qd + SOF 400 mg qd + RBV Not randomised.

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Presentation transcript:

ALLY-1  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml) in genotype 1 DCV 60 mg qd + SOF 400 mg qd + RBV DCV 60 mg qd + SOF 400 mg qd + RBV Not randomised Open-label ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence W12 N = 53 ≥ 18 years Chronic HCV infection All genotypes Treatment-naïve or experienced NS5A inhibitor-naïve Advanced cirrhosis* or post- liver transplant recurrence** Poordad F. EASL 2015, Abs. L08 Post-transplant recurrence SVR 12 N = 60 Advanced cirrhosis * Child-Pugh A, B or C, MELD score 8-40, hepatocarcinoma allowed ** ≥ 3 months post-transplant, no rejection, any immunosuppressive regimen RBV : 600 mg/day (bid dosing), adjusted to 1000 mg/day, based on hemoglobin and creatinine clearance

Advanced cirrhosis N = 60 Post-transplant N = 53 Median age, years5859 Female37%28% HCV RNA log 10 IU/ml, mean IL28B CC genotype22%25% Genotype 1a 1b % 18% 8% 10% 7% 0 58% 19% 0 21% 0 2% Fibrosis stage by Fibrotest : F0-F2 / F3 / F4-43% / 35% / 30% Baseline characteristics  Advanced cirrhosis cohort –Child Pugh A = 12 (MELD score : 5/12) –B = 32 (2/3 with ascites and/or encephalopathy, MELD score : 25/32) –C = 16 (all with ascites and encephalopathy ; MELD score ≥ 16 : 13/16) ALLY-1 ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence Poordad F. EASL 2015, Abs. L08

SVR 12 (HCV RNA < 25 IU/ml) Advanced fibrosis Post-transplant % N Hepatic encephalopathy ABYesCNo Albumin g/dl Yes≥ 2.8 Genotype 1 AllNo Child-PughAscites < 2.8 GT 1aOther genotypes ALLY-1 ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence Poordad F. EASL 2015, Abs. L08

 NS5A variants (-28, -30, -31, or -93 polymorphisms) detected in 22 of 112 patients –82% (18/22) achieved SVR 12 10/14 in cirrhosis cohort ; 8/8 in post-transplant cohort –90% (81/90) without NS5A polymorphisms achieved SVR 12 39/45 in cirrhosis cohort ; 42/45 in post-transplant cohort  No NS5B-S282 variants detected at baseline or failure Advanced cirrhosisPost-transplant Virologic failures, N10 (9 relapses)3 (all relapses) NS5A RAVs at baseline, n/N * 4/100/3 NS5A RAVs at failure, n/N * 10/103/3 * Assessed by population-based sequencing ALLY-1 ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence Poordad F. EASL 2015, Abs. L08 NS5A resistance-associated variants in patients with virologic failure Baseline resistance polymorphisms

Advanced cirrhosis N = 60 Post-transplant N = 53 Death00 Serious adverse event10 (17%), all unrelated5 (9%), all unrelated Grade 3 or 4 adverse event*11 (18%)4 (8%) Discontinuations due to adverse event All study medications1 (2%) RBV only10 (17%)4 (8%) AE (any grade) in ≥ 10% in either cohort Headache9 (15%)19 (36%) Fatigue11 (18%)15 (28%) Anemia12 (20%)10 (19%) Diarrhea5 (8%)10 (19%) Nausea10 (17%)3 (6%) Arthralgia1 (2%)7 (13%) * 4 events (anemia, non-cardiac chest pain, arthralgia, headache) considered related to study medication Adverse events, n (%) ALLY-1 ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence Poordad F. EASL 2015, Abs. L08

 Summary –SVR 12 achieved by 94% of liver transplant recipients with HCV recurrence Favorable drug-drug interaction profile that did not require dose modification of pre-transplant or immunosuppressant medications No events of graft rejection –SVR 12 in 92% of patients with Child-Pugh class A cirrhosis, 94% in class B, 56% in class C –High SVR 12 rates in GT-3 patients: 83% of advanced cirrhosis, 91% of post-transplant –SVR 12 rate of only 76% in genotype 1 advanced cirrhosis ALLY-1 Poordad F. EASL 2015, Abs. L08 ALLY-1 Study: DCV + SOF + RBV for advanced liver disease and post-liver transplant recurrence