Design CBREEZE2 Lawitz E AASLD 2017 Abs 61 RZR 180 mg QD UPR 450 mg QD SVR 12 RZR UPR W12 W0 1870 years HCV genotype 16 Treatment naïve or experienced no prior DAA HCV RNA 10000 IUml ID: 766213
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Design C-BREEZE-2 Lawitz E. AASLD 2017, Abs. 61 RZR : 180 mg QD ; UPR : 450 mg QD SVR 12 RZR + UPR W12 W0 18-70 yearsHCV genotype 1-6Treatment naïve or experienced (no prior DAA)HCV RNA ≥ 10,000 IU/mlNo cirrhosis or compensated cirrhosis *HIV co-infection allowedNo HBV co-infection ObjectiveSVR12 (HCV RNA < 15 IU/mL), full analysis set (FAS) : all participants who received ≥ 1 dose of study medication ; mFAS : exclusion of participants with non-virologic failure N = 250 * Liver biopsy or Fibroscan® > 12.5 kPa or FibroSure® > 0.75 + APRI > 2 2 cohorts: initial enrollment of 50 participants, and continue enrollment for a total of 250 patients if no safety criteria are met C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6
RZR + UPR 12W N = 282 Mean age , years 49.5 Female, % 45 Race : White / Asian / Black, % 78 / 10 / 8 Cirrhosis, % 21 Genotype 1a / 1b / 2 / 3 / 4 / 5 / 6, % 17 / 11 / 17 / 22 / 21 / 6 / 8 IFN treatment-experienced, % 16 SVR 12 FAS mFAS **90% *92% Baseline characteristics and SVR12 Lawitz E. AASLD 2017, Abs. 61 C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6 * 19 relapses , 2 discontinuations due to drug-related adverse events** 8 patients excluded (7 discontinuations, 1 lost to follow-up) C-BREEZE-2
Lawitz E. AASLD 2017, Abs. 61 SVR12 , mFAS, by genotype, %* GT1a: 3 relapses** GT2 : 1 non- compliance, 1 discontinuation due to drug-related adverse event (insomnia and fatigue)*** GT3: 14 relapses (SVR12 : 80% in non-cirrhotics vs 68% in cirrhotics) **** GT6 : 1 relapse, 1 discontinuation due to drug-related adverse event (anxiéty and nausea)C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6 C-BREEZE-2 259 45 304559 55322
% 25 50 100 75 79 57 82 N 52 7 28 A30 Any of 7 positions *3154533 26 6980408 67 4 100 432311479980SVR12, mFAS, according to baseline NS5A RAS in genotype 3 and 1a, %Y93 S62Y93 Any of 4positions ** Genotype 3 Genotype 1a* 24, 28, 30, 31, 58, 62, 93** 28, 30, 31, 93 (detection par next-generation sequencing with 15% sensitivity No RAS RAS present C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6 C-BREEZE-2 Lawitz E. AASLD 2017, Abs. 61
Adverse events, % Lawitz E. AASLD 2017, Abs. 61 RZR + UPR 12W N = 282 Any adverse event 61 Drug-related adverse event Fatigue Headache33.37.87.4 Discontinuation due to adverse event 0.7 Serious adverse event 2.5 Discontinuation due to serious adverse event 0C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6C-BREEZE-2
SummaryOverall efficacy of the 2-drug regimen of ruzasvir + uprifosbuvir is suboptimalLower efficacy in genotype 3; baseline RAS account for many failuresHigh efficacy in other genotypes; potential impact of baseline Y93 RAS in GT1a, no impact of baseline RAS in other non-GT3 genotypes Good safety profile Lawitz E. AASLD 2017, Abs. 69 C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6 C-BREEZE-2