SOLAR-1 LDV/SOF + RBV Randomisation* of the 7 groups 1 : 1 Open-label SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease  Design W12W24 ≥ 18 years.

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Presentation transcript:

SOLAR-1 LDV/SOF + RBV Randomisation* of the 7 groups 1 : 1 Open-label SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease  Design W12W24 ≥ 18 years Chronic HCV infection Genotypes 1 or 4 Cirrhosis or previous liver transplantation No prior exposure to NS5A inhibitor No HBV or HIV co-infection Charlton M. Gastroenterology 2015 ; 149: N = 30 N = 26 N = 4 N = 26 Child-Pugh B N = 23 N = 55 N = 5 N = 40 LDV/SOF + RBV Child-Pugh C No cirrhosis Child-Pugh B Chid-Pugh A Child-Pugh C Fibrosing cholestasic hepatitis N = 29 N = 25 N = 2 N = 26 N = 56 N = 4 LDV/SOF 90mg/400 mg : 1 pill qd RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) ; dose escalation in Child-Pugh B and C Cohort A Cirrhosis No transplantation Cohort B Prior liver transplantation

SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease Baseline characteristics in Cohort A (cirrhosis, pre-transplantation), median or % Charlton M. Gastroenterology 2015 ; 149: SOLAR-1 Cohort A Child-Pugh BChild-Pugh C 12W24W12W24W Age, years Female27%38%39%31% Genotype 1a 1b 4 63% 33% 3% 76% 24% 0 65% 26% 9% 69% 31% 0 HCV RNA, log 10 IU/ml Previous HCV therapy PEG-IFN + RBV PI + PEG-IFN + RBV Other 73% 45% 41% 17% 66% 53% 47% 0 48% 73% 18% 9% 69% 94% 0 6% Non-response68%74%64%72% Relapse/breakthrough32%26%36%28% eGFR, ml/min

SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease Baseline characteristics (post-transplantation), median or % Charlton M. Gastroenterology 2015 ; 149: SOLAR-1 Cohort B No cirrhosisChild-Pugh AChild-Pugh BChild-Pugh C Fibrosing cholestatic hepatitis 12W24W12W24W12W24W12W24W12W24W Age, years Female16% 27%12%15%12%0000 Genotype 1a 1b 4 73% 25% 2% 71% 29% 0 65% 35% 0 68% 32% 0 77% 23% 0 69% 27% 4% 80% 20% 0 75% 25% 0 75% 25% 0 100% 0 HCV RNA, log 10 IU/ml Previous HCV therapy PEG-IFN + RBV PI + PEG-IFN + RBV Other 71% 67% 23% 10% 86% 81% 10% 8% 85% 68% 14% 18% 96% 75% 17% 8% 85% 55% 36% 9% 85% 77% 18% 5% 80% 100% 0 100% 75% 25% 0 100% 0 50% 100% 0 Non-response59%69%64%79%68%73%75% 100% Relapse/breakthrough41%31%36%21%32%27%25% 00 Years since transplant eGFR, ml/min

Virologic response Charlton M. Gastroenterology 2015 ; 149: SOLAR-1 Cohort B No cirrhosisChild-Pugh AChild-Pugh BChild-Pugh C Fibrosing cholestatic hepatitis 12W24W12W24W12W24W12W24W12W24W N SVR 12 (HCV RNA < 15 IU/ml) 96%98%96% 85%88%60%75%100% Virologic failure, N Breakthrough Relapse Cohort A Child-Pugh BChild-Pugh C 12W24W12W24W N SVR 12 (HCV RNA < 15 IU/ml)87%89%86%87% Virologic failure, N Breakthrough Relapse SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease

 Virologic resistance –Relapse in 7% (3/42) with baseline NS5A resistance-associated variants versus 4% (10/269) in patients without baseline NS5A RAVs –No relapse in patients treated 24 weeks –Of the 13 relapses, 11 (85%) had emergence of NS5A RAVs –M28T –Q30H/R –H58D –Y93H/C Charlton M. Gastroenterology 2015 ; 149: SOLAR-1

SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease  Liver transplantation in Cohort A –N = 7 (4 during study treatment and 3 after completing treatment)  Deaths, N = 13 –Cohort A, Child-Pugh B, N = 3 ; Child-Pugh C, N = 3 –Cohort B, Child-Pugh A, N = 2 ; Child-Pugh B, N = 5 ; Child-Pugh C, N = 0  Serious Adverse events, N = 77 (23%) –30 (28.3% in cohort A –47 (20.5%) in cohort B  Discontinuation for adverse event, N = 13 (4%) –5 in Cohort A –8 in cohort B –Reasons for discontinuation : sepsis or infection (n = 3), acute renal failure (N = 2), gastric hemorrhage (N = 1), ALT + AST increase (N = 1), dyspnea (N = 1) Charlton M. Gastroenterology 2015 ; 149: SOLAR-1

SOLAR-1 Study: LDV/SOF + RBV in advanced liver disease  Summary –LDV/SOF + RBV for 12 weeks is an effective treatment for patients with advanced liver disease, including those with decompensated liver function before and after liver transplantation. Extending treatment to 24 weeks was not associated with improved outcomes, although there were no relapses in these groups –Rates of SVR 12 were over 85% in every group of patients with Child- Pugh class B decompensated cirrhosis - in those who had and had not undergone liver transplantation-, as well as those who received 12 and 24 weeks of treatment. –Similar response rates were observed in Child-Pugh class C patients who had not undergone liver transplantation –Results are very encouraging for fibrosing cholestatic hepatitis which may now be a manageable complication of liver transplantation –SVR 12 in patients with decompensated cirrhosis was associated with early improvements in Child-Pugh and MELD scores –Patients with decompensated liver disease experienced high frequencies of RBV hematotoxicity Charlton M. Gastroenterology 2015 ; 149: SOLAR-1