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OBV/PTV/r Open label 18-70 years Chronic HCV infection Genotype 1b Treatment-naïve or failure to PEG-IFN + RBV HCV RNA > 10,000 IU/ml Without or with cirrhosis* No HBV or HIV co-infection W12 SVR 12 * Metavir F4 or Ishak > 4 or Fibroscan > 14.6 kPa or FibroTest, Child score ≤ 6 N = 82 N = 99 No cirrhosis PEARL-I Study – Part 2 : ombitasvir/paritaprevir/ritonavir + ribavirin for HCV genotype 1b PEARL-I Part 2 Treatment regimen –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg QD = 2 tablets Objective –SVR 12 (HCV RNA < 25 IU/ml) with 95% CI : hypothesis of a 25% difference between treatment-naïve (95%) and prior null-responders without cirrhosis (70%), 80% power with two-sided significance level of 0.05, analysis by intention-to-treat W24 Cirrhosis SVR 12 Design Lawitz E. Gastroenterology 2015, July 2, epub ahead of print
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PEARL-I Study – Part 2 : ombitasvir/paritaprevir/ritonavir + ribavirin for HCV genotype 1b No cirrhosisCirrhosis Treatment- naïve N = 42 Prior null- response N = 40 Treatment- naïve N = 47 Treatment- experienced N = 52 Mean age, years56545857 Female40%62%51%36% White / Black64% / 26%97% / 2%94% / 0100% / 0 Fibrosis stage: F2 / F3 / F433% / 14% / 013% / 13% / 00 / 0 / 100% IL28B CC genotype32%5%17%10% HCV RNA log 10 IU/ml, mean6.4 6.36.5 Prior PEG-IFN + RBV response Relapse / Partial response / Null response - 0 / 100% - 23% / 29% / 48% Discontinued treatment, N2140 Virologic failure Adverse event Other 002002 100100 031031 - Baseline characteristics and patient disposition Lawitz E. Gastroenterology 2015, July 2, epub ahead of print PEARL-I Part 2
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Prior null-responders without cirrhosis, N = 4 (1 virologic breakthrough, 3 relapses) Prior null-responder with cirrhosis, N = 1 (relapse) IL28B CT : 5/5 SVR 12 (HCV RNA < 25 IU/mL), % (95% CI) Virologic failure, N = 5 Treatment-experiencedNaïve Prior null-response No cirrhosis (12W of treatment)Cirrhosis (24W of treatment) 25 50 100 75 95.2 (83.8-99.4) 90 (76.3-97.2) % 97.9 (88.7-99.9) N424047 No differences between groups 0 52 96.2 (86.8-99.5) Lawitz E. Gastroenterology 2015, July 2, epub ahead of print PEARL-I Part 2 PEARL-I Study – Part 2 : ombitasvir/paritaprevir/ritonavir + ribavirin for HCV genotype 1b
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Resistance-associated variants at baseline Characteristics : all prior null-responders Type of failure NS3 RAVNS5A RAV BaselineAt failureBaselineAt failure No cirrhosisBreakthroughNoneY56H + D168AY93HP58S + Y93H No cirrhosisRelapseNoneD168VNoneY93H No cirrhosisRelapseNoneD168VP58S + Y93H No cirrhosisRelapseNoneD168VNoneY93H CirrhosisRelapseNoneD168VNoneY93H Resistance-associated variants at virologic failure Lawitz E. Gastroenterology 2015, July 2, epub ahead of print PEARL-I Part 2 PEARL-I Study – Part 2 : ombitasvir/paritaprevir/ritonavir + ribavirin for HCV genotype 1b No cirrhosisCirrhosis Treatment- naïve N = 39 Prior null- response N = 40 Treatment- naïve N = 46 Treatment- experienced N = 51 NS3 RAV, N1010 NS5A RAV, N61019
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Adverse events, N or % Lawitz E. Gastroenterology 2015, July 2, epub ahead of print PEARL-I Part 2 PEARL-I Study – Part 2 : ombitasvir/paritaprevir/ritonavir + ribavirin for HCV genotype 1b No cirrhosisCirrhosis Treatment- naïve N = 42 Prior null- response N = 40 Treatment- naïve N = 47 Treatment- experienced N = 52 AE leading to discontinuation0030 Serious adverse event1132 Adverse event in ≥ 10% Asthenia7%5%21%14% Back pain0013%8% Diarrhea14%015%14% Dry skin17%02%0 Fatigue14%09%2% Headache33%25%19%17% Hypertension03%15%2% Nausea19%011%10% Pruritus14%017%15% Death001 (GI hemorrhage)0
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PEARL-I Study – Part 2 : ombitasvir/paritaprevir/ritonavir + ribavirin for HCV genotype 1b Summary –An interferon- and ribavirin-free regimen of ombitasvir, paritaprevir, and ritonavir, achieved rates of SVR 12 > 90% in patients with HCV genotype 1b infection with and without cirrhosis, with a 24-weeks or 12-weeks duration of treatment, respectively SVR 12 was 95-98% in naïve patients SVR 12 was 90-96% in treatment-experienced patients –There were few virologic failures, all occurring in prior null responders (failure rate 5/65 = 7.6%), who also harbored CT IL28B genotype All 5 patients had NS3 and NS5A RAVs at failure –The regimen was well tolerated and was associated with low rate (1.7%) of treatment discontinuation The majority of adverse events were mild in severity Lawitz E. Gastroenterology 2015, July 2, epub ahead of print PEARL-I Part 2
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