OBV/PTV/r + DSV

Open label

Chronic HCV infectionGenotype 1

Treatment-naïve HCV RNA > 1,000 IU/mlChronic kidney disease

witheGFR < 30 ml/min/1.73m2

(dialysis permitted)No cirrhosis**

No HBV or HIV co-infection

RUBY-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for HCV genotype 1 with renal impairment

SVR12

** Liver biopsy or fibroscan < 14.6 kPa or FibroTest ≤ 0.72 + APRI ≤ 2

OBV/PTV/r DSV + RBV

N = 7

Genotype 1a

Genotype 1b

N = 13

Pockros PJ. AASLD 2015, Abs. 1039RUBY-I

Design

Treatment regimens– Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r): 25/150/100 mg qd = 2 tablets– Dasabuvir (DSV): 250 mg bid– RBV 200 mg qd (genotype 1a), dosed 4h prior to start of hemodialysis (if applicable)

Objective– SVR12 (HCV RNA < 25 IU/ml)

W12

Baseline characteristics and outcome

* 2 failures– 1 death at D14 after the end of treatment (unrelated cardiac cause) ; HCV RNA undetectable– 1 relapse : black male, 49, GT1a, F3, IL28B CT, RBV discontinued at D58 due to anemia,

compliance not optimal, RAVs emergence at failure : NS3 (D168V) and NS5A (Q30R)

Pockros PJ. AASLD 2015, Abs. 1039RUBY-I

N = 20Median age, years 60Female 15%Race : white / black 30% / 70%Body mass index, mean 30.5Genotype 1a / 1b, N 13 / 7Fibrosis stage F0-F1 / F2 / F3, N 10 / 6 / 4IL28B CC genotype 30%HCV RNA log10 IU/ml, median 6.57History of diabetes 11 (55%)eGFR 15-30 ml/min/1.73 m2 (CKD stage 4), NeGFR < 15 ml/min/1.73 m2 or dialysis (CKD stage 5), N

614

SVR12 (HCV RNA < 25 IU/ml) 18/20 (90%) *

RUBY-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for HCV genotype 1 with renal impairment

Adverse events and laboratory abnormalities, N (%)

Pockros PJ. AASLD 2015, Abs. 1039RUBY-I

RUBY-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for HCV genotype 1 with renal impairment

OBV/PTV/r + DSV + RBVN = 13 (Genotype 1a)

OBV/PTV/r + DSVN = 7 (Genotype 1b)

Serious adverse event 3 (23) 1 (14)Adverse event related to study drug 8 2Adverse event leading to discontinuation 0 0Adverse event leading to RBV dose reduction 9 (69) NAAdverse event in > 15% in any group

Anemia 9 (69) 0Fatigue 5 (38) 2 (29)Diarrhea 4 (31) 1 (14)Nausea 5 (38) 0Headache 3 (23) 0Peripheral edema 1 (8) 2 (29)

Hemoglobin < 10-8 g/dl / < 8-6.5 g/dl, N 7 / 1 2 / 0Total bilirubin > 1.5 to 4 x ULN, N 2 0ALT or AST grade 3 0 0

Pockros PJ. AASLD 2015, Abs. 1039RUBY-I

RUBY-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for HCV genotype 1 with renal impairment

Summary– In HCV genotype 1-infected patients with stage 4 or 5 chronic kidney

disease, including patients on dialysis, 12 weeks of therapy achieved a SVR12 of 90% overall

– Among patients with post-treatment data available, the SVR12 rate was• For genotype 1a : 92.3% (12/13) with OBV/PTV/r + DSV + RBV ; 1 relapse,

possibly related to poor treatment compliance• For genotype 1b : 100% (7/7) with OBV/PTV/r + DSV

– OBV/PTV/r + DSV ± RBV was well tolerated with no treatment discontinuations

– The majority of patients receiving RBV 200 mg/day required RBV interruption

– Laboratory abnormalities and safety findings were otherwise consistent with the safety profile in patients with normal renal function

– These data support the use of the 3D regimen with no dose adjustment in patients with severe or end-stage renal disease