Daclatasvir + Asunaprevir in Genotype 1b HALLMARK-DUAL Study

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Presentation transcript:

Daclatasvir + Asunaprevir in Genotype 1b HALLMARK-DUAL Study Phase 3 Treatment-Naïve and Treatment-Experienced Daclatasvir + Asunaprevir in Genotype 1b HALLMARK-DUAL Study Manns M, et al. Lancet. 2014;384:1597-605.

Daclatasvir + Asunaprevir for HCV GT 1b HALLMARK-DUAL: Study Features Daclatasvir + Sofosbuvir Trial: Features Design: Phase 3 open-label multi-cohort study of daclatasvir (DCV) plus asunaprevir in treatment-naïve or experienced, chronic HCV GT 1b Setting: 18 countries in North & South America, Europe and Asia Entry Criteria - Chronic HCV Genotype 1b - Treatment-naïve or treatment-experienced (prior null or partial responder to peginterferon + ribavirin) - Ineligible or intolerant (or both) to peginterferon + ribavirin - Compensated cirrhosis allowed Patient Groups - N = 307 treatment-naïve randomized to DCV + asunaprevir x 24 weeks versus placebo (latter then enrolled in separate DCV study) - N = 205 treatment-experienced: DCV + asunaprevir x 24 weeks - N = 235 Peg/RBV intolerant +/- ineligible: DCV + asunaprevir x 24 weeks End-Points: Primary = SVR12 Source: Manns M, et al. Lancet. 2014;384:1597-605.

Daclatasvir + Asunaprevir for HCV GT 1B HALLMARK-DUAL: Study Design Week 24 12 36 Treatment Naïve n = 307 n = 205 Daclatasvir + Asunaprevir SVR12 n = 102 Placebo Separate daclatasvir study Prior Non-responder n = 205 Daclatasvir + Asunaprevir SVR12 Intolerant +/- Ineligible n = 235 Daclatasvir + Asunaprevir SVR12 Drug Dosing Daclatasvir: 60 mg once daily Asunaprevir: 100 mg twice daily Source: Manns M, et al. Lancet. 2014;384:1597-605.

Treatment-naïve on DCV + ASV Treatment-naïve on Placebo Daclatasvir + Asunaprevir for HCV GT 1B HALLMARK-DUAL: Patient Characteristics Characteristic Treatment-naïve on DCV + ASV (n=205) Treatment-naïve on Placebo (n=102) Prior Non-responder Intolerant/ Ineligible (n=235) Age (years) 55 (20-79) 54 (22-83) 58 (23-77) 60 (24-77) Men 101 (49%) 54 (53%) 111 (54%) 98 (42%) Race White Black Asian 135 (66%) 14 (7%) 52 (25%) 59 (58%) 8 (8%) 45 (22%) 148 (72%) 10 (5%) 169 (72%) 10 (4%) 56 (24%) HCV RNA ≥800,000 IU/ml 152 (74%) 76 (75%) 178 (87%) 187 (80%) Cirrhosis 33 (16%) 16 (16%) 63 (31%) 111 (47%) Prior response to P/R Null Partial N/A 119 (58%) 84 (41%) Ineligible/intolerant reason Depression Anemia/neutropenia Advanced F3 or F4a 71 (30%) 87 (37%) 77 (33%) DCV=daclatasvir; ASV=asunaprevir. aCompensated (Child A) if cirrhotic but with thrombocytopenia. Source: Manns M, et al. Lancet. 2014;384:1597-605.

Daclatasvir + Asunaprevir in Genotype 1b HALLMARK-DUAL Study HALLMARK-DUAL: SVR12, by Treatment Experience 547/643 184/203 169/205 194/235 Source: Manns M, et al. Lancet. 2014;384:1597-605.

Daclatasvir + Asunaprevir in Genotype 1b HALLMARK-DUAL Study HALLMARK-DUAL: SVR12, by Cirrhosis Status 172/206 370/437 29/32 153/171 55/63 113/142 88/111 104/124 Source: Manns M, et al. Lancet. 2014;384:1597-605.

Daclatasvir + Asunaprevir for HCV GT 1B HALLMARK-DUAL: Adverse Events Adverse Effects Treatment-naïve on DCV + ASV (n=205) Treatment-naïve on Placebo (n=102) Prior Non-responder Intolerant/Ineligible (n=235) Any adverse event 176 (86%) 74 (73%) 167 (81%) 204 (87%) Serious adverse events 12 (6%) 1 (1%) 11 (5%) 16 (7%) Adverse events leading to discontinuation 6 (3%) 2 (1%) Adverse events in ≥10% in any cohort Headache Fatigue Diarrhea Nausea Asthenia 50 (24%) 43 (21%) 24 (12%) 25 (12%) 4 (2%) 17 (17%) 18 (18%) 10 (10%) 12 (12%) 45 (22%) 28 (14%) 22 (11%) 59 (25%) 52 (22%) 51 (22%) 28 (12%) 25 (11%) Grade 3-4 lab events ALT 5.1-10 x ULN ALT >10 x ULN AST 5.1-10 x ULN AST >10 x ULN 1 (<1%) 5 (2%) 2 (2%) 3 (1%) ULN, upper limit of normal Source: Manns M, et al. Lancet. 2014;384:1597-605.

Daclatasvir + Asunaprevir for HCV GT 1b HALLMARK-DUAL: Conclusions Interpretation: “Daclatasvir plus asunaprevir provided high sustained virological response rates in treatment-naive, non-responder, and ineligible, intolerant, or ineligible and intolerant patients, and was well tolerated in patients with HCV genotype 1b infection. These results support the use of daclatasvir plus asunaprevir as an all-oral, interferon- free and ribavirin-free treatment option for patients with HCV genotype 1b infection, including those with cirrhosis.” Source: Manns M, et al. Lancet. 2014;384:1597-605.

This slide deck is from the University of Washington’s Hepatitis C Online and Hepatitis Web Study projects. Hepatitis C Online www.hepatitisc.uw.edu Hepatitis Web Study http://depts.washington.edu/hepstudy/ Funded by a grant from the Centers for Disease Control and Prevention.