UNITY-1 DCV/ASV/BCB No randomisation Open-label UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis  Design W12 ≥ 18 years.

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Presentation transcript:

UNITY-1 DCV/ASV/BCB No randomisation Open-label UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis  Design W12 ≥ 18 years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/ml Naïve or pre-treated with IFN- based regimen No cirrhosis* No HBV or HIV co-infection N = 415 SVR 12 * Liver biopsy with Metavir < F4, or Fibrotest ® ≤ APRI < 1, or Fibroscan kPa ≤ 9.6 Co-formulated DCV/ASV/BCB 30/100/75 mg qd : 1 pill bid  Objective –Primary endpoint : SVR 12 (HCV RNA 79%, rate of historical control (SVR achieved in this population with SOF + PEG-IFN + RBV) –Secondary endpoint : SVR 12 (HCV RNA 49%, rate of historical control (composite SVR in this population with SMV + PEG-IFN + RBV), 95% power Poordad F. JAMA 2015;313:

Treatment- naïve N = 312 Treatment- experienced N = 103 Median age, years Female44%38% Race : white / black87% / 11%88% / 7% Genotype : 1a / 1b73% / 27% IL28B CC genotype29%16% HCV RNA > 800,000 IU/ml78%90% Prior IFN-based treatment, N (%)-90.3% Relapse37.9% Null response24.3% Partial response11.7% Interferon intolerant6.8% Indeterminate9.7% Discontinuation, N74 Lack of virologic response / adverse event / pregnancy6 / 0 / 11 / 3 / 0 Baseline characteristics and patient disposition UNITY-1 UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis Poordad F. JAMA 2015;313:

SVR 12 (HCV RNA < 25 IU/ml), % (95% CI) * ( ) % 92* (89-95) 1a N 1b Non-response32 Virologic breakthrough62 Relapse156  SVR 12 comparable across subgroups : –Gender –Age –HCV RNA level –IL28B genotype * Superior to historical control All patients UNITY-1 UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis Poordad F. JAMA 2015;313: NaïveExperienced

 Resistance analysis –Genotype 1a : 32 virologic failures NS5A resistance-associated variants in 28/29 (most frequent : Q30) NS3 RAVs in 25/26 (most frequent : R155) NS5B RAVs in 12/28 (most frequent : P495) –Genotype 1b : 2 virologic failures –Baseline NS5A polymorphims (28, 30, 31, 93) associated with resistance to DCV Genotype 1a : 34/102 (11%) : SVR 12 in 25/34 (74%) Genotype 1b : 17/106 (16%) : SVR 12 in 17/17 (100%) –Baseline NS3 and NS5B variants did not affect SVR 12 UNITY-1 UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis Poordad F. JAMA 2015;313:

Adverse events and laboratory abnormalities, N UNITY-1 N = 415 Discontinuation for adverse event3 (0.7%) Serious adverse event7 (1.7%) Adverse event in > 10% of patients Headache25.8% Fatigue16.6% Diarrhea14.0% Nausea13.5% Grade 3-4 laboratory abnormalities Hemoglobin < 9 g/dl0 Lymphocytes < 0.5 x 10 9 /l1 (0.2%) Neutrophils < 0.75 x 10 9 /l2 (0.5%) ALT > 5 x ULN19 (4.6%) AST > 5 x ULN9 (2.2%) Lipase > 3 x ULN16 (3.9%) UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis Poordad F. JAMA 2015;313:

 Summary –In this open-label, uncontrolled study, 12 weeks of treatment with a fixed- dose combination of daclatasvir, asunaprevir and beclabuvir in HCV genotype 1-infected patients without cirrhosis was associated with high SVR 12 92% in treatment-naive patients 89% in patients previously treated for HCV infection SVR 12 rates were higher with genotype 1b than with genotype 1a in both the treatment-naive (98% vs 90%, respectively) and -experienced (100% vs 85%, respectively) cohorts –There were low rates of serious AEs and treatment discontinuations –All genotype 1b-infected patients with baseline NS5A polymorphisms achieved SVR1 2 while only 74% with genotype 1a had SVR 12 –Resistance-associated variants at amino acids positions NS5A-Q30, NS3-R155K and NS5B-P495 were observed most frequently at viral breakthrough; NS5B variants were generally not observed in patients experiencing relapse UNITY-1 UNITY-1 Study: daclatasvir/asunaprevir/beclabuvir in genotype 1 without cirrhosis Poordad F. JAMA 2015;313: