SOF + RBV Randomisation* 1 : 1 : 1 Open-label BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 ≥ 18 years Chronic HCV infection Genotype 2, treatment-

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VALENCE SOF + RBV Not randomised Open label* ≥ 18 years Chronic HCV infection Genotype 2 or 3 HCV RNA ≥ 10,000 IU/ml Treatment naïve or prior IFN-based.

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Presentation transcript:

SOF + RBV Randomisation* 1 : 1 : 1 Open-label BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 ≥ 18 years Chronic HCV infection Genotype 2, treatment- experienced with cirrhosis Genotype 3, naïve or experienced, with or without cirrhosis No HBV or HIV co-infection SOF + PEG- IFN + RBV * Randomisation was stratified on genotype (2 or 3), prior therapy (yes or no) and cirrhosis (presence or absence) N = 196 N = 199 N = 197 SVR 12 –SOF 400 mg) : 1 pill QD –RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) –PEG-IFNa-2a : 180 mg SC once weekly  Objective –SVR 12 (HCV RNA < 15 IU/ml) SVR 12 BOSON Foster GR. Gastroenterology Nov;149(6):  Design W24W16 W12

BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 SOF + RBV 16W N = 196 SOF + RBV 24W N = 199 SOF + PEG-IFN + RBV 12W N = 197 Mean age, years Female32%35%33% Asian14%13% Genotype 392% Cirrhosis37% 38% IL28B CC genotype38%37%40% HCV RNA log 10 IU/ml, mean Treatment-experienced54%53%52% BOSON Baseline characteristics Foster GR. Gastroenterology Nov;149(6):

BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 BOSON SVR 12 (HCV RNA < 15 IU/ml), % (95% CI) SOF + RBV 16WSOF + RBV 24WSOF + PEG-IFN + RBV 12W Genotype 2Genotype 3 All patients –In genotype 3, higher SVR 12 with SOF + PEG-IFN + RBV 12W compared to SOF + RBV for 16W or 24W, particularly in patients with cirrhosis and/or prior treatment 15 % /11283/100 10/ Treatment NaïveTreatment Experienced TN no cirrhosisTN cirrhosisTE no cirrhosis TE cirrhosis % Genotype 3 by subgroup Foster GR. Gastroenterology Nov;149(6):

BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 BOSON SVR 12 in GT 3 SOF + RBV 16WSOF + RBV 24WSOF + PEG-IFN + RBV 12W n SVR 12 (%) No CirrhosisCirrhosis Treatment History NaïveExperienced Foster GR. Gastroenterology Nov;149(6):

BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 Reasons for not achieving SVR 12 Resistance analysis BOSON  Deep sequencing successful on 78/88 patients with virologic failure –No S282T variants –SOF treatment-emergent variants L159F and V321A in 9/78 (21%) L159F at baseline and failure, N = 1, only at failure, N = 5 V321A emerged at failure in 2 patients Patients, n (%) SOF + RBV 16W N = 196 SOF + RBV 24W N = 199 SOF + PEG-IFN + RBV 12W N = 197 SVR (72)170 (85)183 (93) On-treatment failure03 (2)0 Relapse52/195 (27)24/195 (12)9/195 (5) Other*3 (2)2 (1)5 (3) * Patients who discontinued before achieving HCV RNA < LLOQ or did not return for week 12 post-treatment visit Foster GR. Gastroenterology Nov;149(6):

SOF + RBV 16W N = 196 SOF + RBV 24W N = 199 SOF + PEG-IFN + RBV 12W N = 197 Grade 3–4 adverse event11 (6)7 (4)15 (8) Serious adverse event8 (4)10 (5)12 (6) Treatment discontinuation due to AE3 (2)2 (1)1 (< 1) Adverse event ≥ 15% in any arm Fatigue 36%41%46% Headache 31%36% Insomnia 24%28%25% Nausea16%17%25% Rash12%14%20% Flu-like illness4% 19% Decreased appetite7%8%18% Myalgia6%10%17% Dyspnea exertional11% 15% Pyrexia3%4%15% Hemoglobin < 10g/dl / 8.5 g/dL4% / 06% / 012% / 1% BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 BOSON Adverse events, N (%) Foster GR. Gastroenterology Nov;149(6):

BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3  Summary –Genotype 2 : treatment-experienced patients with cirrhosis achieved high SVR 12 rates with all regimens –Genotype 3 : higher SVR 12 rates with SOF + PEG/RBV than with SOF + RBV for 16 or 24 weeks Genotype 3 treatment-experienced patients with cirrhosis achieved an SVR 12 of 86% with SOF + PEG + RBV for 12 weeks –SOF + RBV for 24 weeks achieved SVR 12 rates > 80% in all other subgroups; results consistent with earlier phase III studies –SOF + RBV for 16 or 24 weeks and SOF + PEG + RBV for 12 weeks were well tolerated with a low rate of treatment discontinuations due to adverse events BOSON Foster GR. Gastroenterology Nov;149(6):