P0898 : TD-6450, A next generation once-daily NS5A inhibitor, has potent antiviral activity following a 3-day monotherapy study in genotype 1 HCV infection

ABT-493 is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530 is an HCV NS5A inhibitor. These direct-acting antivirals (DAAs) demonstrated potent antiviral activity against major HCV genotypes and high barriers to resistance in vitro. In this open-label dose-ranging trial, antiviral activity and safety were assessed during 3 days of monotherapy with ABT-493 or ABT-530 in treatment-naive adults with HCV genotype 1 infection, with or without compensated cirrhosis. The presence of baseline resistance-associated variants (RAVs) was also evaluated. The mean maximal decreases in HCV RNA levels from baseline were approximately 4 log10 IU/ml for all ABT-493 doses ranging from 100 mg to 700 mg and for ABT-530 doses of ≥40 mg. There were no meaningful differences in viral load declines for patients with versus without compensated cirrhosis. Twenty-four (50%) of the baseline samples from patients treated with ABT-493 had RAVs to NS3/4A protease inhibitors. Among 40 patients treated with ABT-530, 6 (15%) carried baseline RAVs to NS5A inhibitors. Viral load declines in patients with single baseline NS5A RAVs were similar to those in patients without RAVs. One patient harbored baseline RAVs at 3 NS5A positions and appeared to have a slightly less robust viral load decline on day 3 of monotherapy. No serious or grade 3 (severe) or higher adverse events and no clinically relevant laboratory abnormalities were observed with either compound. ABT-493 and ABT-530 demonstrated potent antiviral activity and acceptable safety during 3-day monotherapy in patients with HCV genotype 1 infection, with or without compensated cirrhosis. Based on these results, phase II studies assessing the combination of these DAAs for the treatment of chronic HCV infection in patients with or without compensated cirrhosis have been initiated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01995071.)

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Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection

Lawitz

O’Riordan

Asatryan

et al. 2016

Antimicrob Agents Chemother

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The Liver Meeting 2014

Charles¹

2015

EMJ Hepatol

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Rapid developments in clinical research on the hepatitis C virus infection in the last few years have led to the development of direct-acting antivirals, such as sofosbuvir, simeprevir (both of which have been approved in the US and Europe since 2014), and daclatasvir, which was approved in Europe only in 2014. These new drugs generated a change of paradigm from interferon-based therapies, as the former require shorter treatment durations and provide high cure rates with acceptable toxicity. The 65th American Association for the Study of Liver Diseases (AASLD) Annual Meeting, The Liver Meeting® 2014, took place in Boston, Massachusetts, on 7th-11th November. This review will summarise the highlights of this meeting within the context of pivotal clinical trials and real-life data on this rapidly evolving treatment environment, which will assist clinicians in selecting the most appropriate regimen for patients.

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The Liver Meeting 2014: Summary of Presentations on Genotype 3 HCV Infection from the 65th Annual Liver Meeting of the American Association for the Study of Liver Diseases (AASLD), Held in Boston, MA, USA, on 7th-11th November, 2014

Charles¹

2014

EMJ Hepatol

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After genotype 1 (GT1), genotype 3 (GT3) is the second most common hepatitis C virus (HCV) genotype worldwide, with an estimated worldwide prevalence of 54.3 million. As its high prevalence already represents a significant burden, this genotype appears to be one of the most difficult to treat using all oral therapies, which is of importance as it is associated with more rapid fibrosis progression and disproportionately increased risks of steatosis (fatty liver disease) and hepatocellular carcinoma. Outstanding developments in clinical research in the last few years have led to the development of direct-acting antivirals, but GT3 still represents a challenge yet to be addressed, and is a clear unmet medical need, especially with associated comorbidities (advanced, liver disease, pre and post-transplant patients, HIV/HCV co-infected patients). The 65th American Association for the Study of Liver Diseases Annual Meeting, The Liver Meeting® 2014, took place in Boston, Massachusetts, USA, on 7th–11th November 2014. This review will summarise the highlights of this meeting on the future of GT3 HCV treatment within pivotal clinical trials.

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P0898 : TD-6450, A next generation once-daily NS5A inhibitor, has potent antiviral activity following a 3-day monotherapy study in genotype 1 HCV infection

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Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection

Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection

The Liver Meeting 2014

The Liver Meeting 2014: Summary of Presentations on Genotype 3 HCV Infection from the 65th Annual Liver Meeting of the American Association for the Study of Liver Diseases (AASLD), Held in Boston, MA, USA, on 7th-11th November, 2014

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