ALLY-3  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI DCV 60 mg qd + SOF 400 mg qd Not randomised Open-label ALLY-3 Study: DCV + SOF for.

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Presentation transcript:

ALLY-3  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI DCV 60 mg qd + SOF 400 mg qd Not randomised Open-label ALLY-3 Study: DCV + SOF for HCV genotype 3 W12 N = 51 ≥ 18 years Chronic HCV infection Genotype 3 Treatment-naïve or experienced NS5A inhibitor-naïve HCV RNA ≥ 50,000 IU/ml Cirrhosis* allowed No HBV or HIV co-infection Nelson DR. Hepatology 2015;61: Treatment-experienced SVR 12 N = 101 Treatment-naïve * Metavir F4, or Fibroscan > 14.6 kPa, or Fibrotest ® ≥ APRI > 2

Treatment-naïve N = 101 Treatment-experienced* N = 51 Median age, years5358 Female43%37% White / black91% / 4%88% / 4% HCV RNA ≥ 800,000 IU/ml69%75% IL28B CC genotype40%39% Cirrhosis19%25% Fibrosis stage by Fibrotest, F422%16% Past treatment category Relapse Null response Partial response Other failure (intolerance, breakthrough) - 61% 14% 4% 22% Discontinuation1 (pregnancy)0 Baseline characteristics and patient disposition * 7 patients with previous failure to SOF, and 2 to alisporivir ALLY-3 Study: DCV + SOF for HCV genotype 3 ALLY-3 Nelson DR. Hepatology 2015;61:

SVR 12 (HCV RNA < 25 IU/ml) Treatment-naïve Treatment-experienced By sub-groups  SVR 12 in 5/7 prior failure to SOF and in 2/2 prior failure to alisporivir ALLY-3 Study: DCV + SOF for HCV genotype 3 ALLY-3 Nelson DR. Hepatology 2015;61: * 95 % 73 86** All N F0-F3F4 Baseline HCV RNA, IU/ml MF< 800K< 65≥ 65 IL28B CCNon-CC * 95% CI: **95% CI: Fibrotest AllF0-F3F4≥ 800K GenderAge, years 0

Virologic failure ALLY-3 Study: DCV + SOF for HCV genotype 3  Virologic breaktrough : none  Failure at end of treatment : 1 naïve patient with cirrhosis  Post-treatment relapse – 9 in the naïve group (cirrhosis : 7/9) – 7 in the pre-treated group (cirrhosis : 4/7) – 15/16 occurred by W4 post-treatment – Emergence of resistance-associated variant : 10/16 Y93H, n = 9 L31I, n = 1 – In the 6 other : presence of baseline Y93H variant  No NS5B-resistant variants (159, 282, 321) detected at baseline or relapse ALLY-3 Nelson DR. Hepatology 2015;61:

Adverse events and Grade 3-4 laboratory abnormalities, N (%) N = 152 Adverse event leading to discontinuation0 Serious AE (gastrointestinal hemorrhage, not related)1 Grade 3 AE (arthralgia, food poisoning, GI hemorrage)3 (2%) AE in ≥ 5 % of patients Headache20% Fatigue19% Nausea12% Diarrhea9% Insomnia6% Abdominal pain5% Arthralgia5% Lymphocytes < 500/  l 1 (1%) Platelets < 50 x 10 9 /l2 (1%) INR > 2 x ULN2 (1%) ALT or AST > 5 x ULN or total bilirubin > 2.5 x ULN0 Lipase > 3 x ULN3 (2%) ALLY-3 Study: DCV + SOF for HCV genotype 3 ALLY-3 Nelson DR. Hepatology 2015;61:

ALLY-3 Study: DCV + SOF for HCV genotype 3  Summary –A 12-week regimen of DCV plus SOF achieved SVR 12 in 96% of treatment-naïve and treatment-experienced patients with genotype 3 infection without cirrhosis and was well tolerated –SVR in patients with cirrhosis was sub-optimal –SVR 12 rates were comparable across subgroups based on gender, age, baseline HCV-RNA levels, and IL28B genotype –Among the 16 patients with relapse, 11 had cirrhosis –6/13 patients with baseline Y93H variant had relapse post- treatment, including 3 of 4 patients with cirrhosis –Safety was good with no discontinuation for adverse event ALLY-3 Nelson DR. Hepatology 2015;61: