Daclatasvir present and future DAA combinations (HepDART 2013) - Dec 30, 2013 - Abstract 29; P3, N=222; NCT01497834; Sponsor: Bristol-Myers Squibb; P2b, N=166; "In the phase 3 study of daclatasvir + asunaprevir, SVR24 was achieved by 84.7% of patients overall....In the phase 2b study of the DCV-based 3-DAA regimen, SVR12 was achieved by 92.2% or 91.7% of patients in the arms receiving BMS-791325 75 mg or 150 mg, respectively, without apparent differences associated with GT1 subtype or presence of cirrhosis."
P2 data • P3 data • Hepatitis C Virus
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HepDART, Dec 8-12, 2013; Kamuela, HI, USA
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Abstract 29
BACKGROUND: Daclatasvir is a potent HCV NS5A replication complex inhibitor with pan-genotypic antiviral activity in vitro. Daclatasvir has been studied in over 5500 HCV-infected patients in multiple phase 2 and 3 studies. Daclatasvir can be dosed once- or twice-daily with no food restrictions and has a low potential for drug-drug interactions with concomitant medications including other DAAs.
METHODS: In an open-label phase 3 study, 24 weeks of therapy with daclatasvir (60 mg QD) in combination with the NS3 protease inhibitor asunaprevir (100 mg BID) was evaluated in 222 Japanese interferon ineligible and intolerant patients and prior non-responders with HCV genotype (GT) 1b infection. In a randomized phase 2b study, 12 weeks of therapy with the 3-DAA combination of daclatasvir (30 mg BID), asunaprevir (200 mg BID), and the non-nucleoside NS5B inhibitor BMS-791325 (75 or 150 mg BID) was evaluated in 166 treatment-naïve patients with GT1 (primarily GT1a) infection.
RESULTS: In the phase 3 study of daclatasvir + asunaprevir, SVR24 was achieved by 84.7% of patients overall. Baseline factors historically associated with reduced SVR rates, including IL28B non-CC genotype, male gender, advanced age, high baseline HCV RNA, and cirrhosis, did not appear to impact response rates. In the phase 2b study of the DCV-based 3-DAA regimen, SVR12 was achieved by 92.2% or 91.7% of patients in the arms receiving BMS-791325 75 mg or 150 mg, respectively, without apparent differences associated with GT1 subtype or presence of cirrhosis. Virologic failure and treatment discontinuations were infrequent. In both studies, daclatasvir was well tolerated, and safety and tolerability parameters suggested a daclatasvir safety profile comparable to that of placebo.
CONCLUSIONS: All-oral, interferon-free and ribavirin-free, daclatasvir-based regimens have achieved high rates of SVR in phase 2 and phase 3 studies, establishing daclatasvir as a versatile contributor to potent HCV regimens for a broad range of patient types. Further phase 3 studies are ongoing.
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