This year's AASLD conference provided a wealth of information about the new direct-acting antiviral agents (DAAs) to treat hepatitis C. I have summarized below some of the more interesting presentations and posters. There is still much information that I am reviewing and I will update the report via our website as needed, and I will include more information and analyses of the most important or interesting data presented at AASLD in the December 2010 HCV Advocate newsletter.
Post-conference highlights: ABT-450 is a protease inhibitor that is being tested in HCV treatment-naïve genotype 1 subjects as a combination therapy that includes ritonavir (boosting agent) and pegylated interferon plus ribavirin. For three days the trial participants were given ABT-450 (boosted with ritonavir) at doses ranging from 50 to 200 once a day followed by quadruple therapy of ABT-450 (with ritonavir) plus pegylated interferon and ribavirin for 12 weeks followed by 36 weeks of pegylated interferon. At the end of week 4, 21 of 23 (91.3%) were HCV RNA negative (<25IU/mL) compared to 1 of 8 (12.5%) of those who received the placebo. The medications were safe and well-tolerated.
Post-conference highlights: ACH-2684 was found to be active against genotypes 1 to 6 (pan genotypic) and was found to work with multiple protease inhibitors. The development of the drug will move forward.
Post-conference highlights: It was found that when ACH-1655 (protease inhibitor) and ACH2928 (NS5A inhibitor) were combined there was a synergistic affect that was enhanced when combined with ribavirin.
Post-conference highlights: There is an ongoing study of ANA598 (in multiple doses) combined with pegylated interferon plus ribavirin. 29 HCV genotype 1 treatment-naïve patients received the triple therapy for 12 weeks and were randomized (depending of treatment response) to an additional 12 or 36 weeks. The SVR 12 results in the patients who completed 24 weeks of treatment was 73% (in eight patients). The most common side effect was rash and it was observed in 59% of the patients who received the 400 mg dose.
Post-conference highlights: In this study (without interferon) the triple regime of BI 201335 (protease inhibitor) plus BI 207127 (polymerase inhibitor) and ribavirin to treat HCV genotype 1 treatment-naïve patients was found to provide strong antiviral activity—additional studies with longer durations are planned to evaluate sustained virological response rates.
Post-conference highlights: In an important study the combination of BMS-650032 (protease inhibitor) and BMS-790052 was given to genotype 1 null-responders to a prior course of therapy. The interim results at 12 weeks (total study duration is 24 weeks) produced early antiviral activity, but 6 out of the 11 people treated had viral breakthrough indicating that pegylated interferon and/or ribavirin will be needed to completely suppress the virus at least in this study. When the combination was combined with pegylated interferon and ribavirin 9 out of 10 patients became HCV RNA undetectable by week 12.
Post-conference highlights: Interim results using various doses of danoprevir combined with pegylated interferon plus ribavirin found that 88 to 92% were HCV RNA negative by week 12 compared to 43% in the placebo group. More studies are planned including a study using ritonavir as a boosting agent.
Post-conference highlights: The combination of GS-9256 (HCV protease inhibitor) plus tegobuvir (GS-9190 – polymerase inhibitor) when combined with pegylated interferon plus ribavirin produced the best results. The quadruple group was given for 4 weeks followed by 44 weeks of pegylated interferon plus ribavirin. 14 out of 14 patients were HCV RNA negative by day 28. There is an ongoing 4 month study of the quadruple therapy.
Post-conference highlights: Vaniprevir—A study of 45 HCV genotype 1 treatment-naïve patients who were administered 1 of 5 regimens—placebo, 300 mg BID (twice a day), 600 mg BID, 600 mg QD (once a day) or 800QD in combination with pegylated interferon plus ribavirin for 4 weeks followed by an additional 44 weeks of pegylated interferon resulted in SVR rates of 78 to 84% compared to 63% in the placebo (only pegylated interferon and ribavirin). Note: the high SVR rate in the placebo group is likely due to the small patient population in this group.
Post-conference highlights: A total of forty healthy volunteers were given PPI-461, an NS5A inhibitor for up to 5 days and it was found that the plasma levels of PPI-461 were reached within 1-4 hours. No serious adverse events were noted. PPI-461 is pan-genotypic (activity against all genotypes). This study warranted exploring a once-a-day dosing in HCV patients.
Post-conference highlights: PSI-352938, a protease inhibitor, was tested in healthy volunteers at doses ranging from 25 to 1600 mg and was found to be generally safe and well-tolerated. Based on this study a mono-therapy study is being conducted in genotype 1 patients.
Post-conference highlights: PSI-7977, a polymerase inhibitor, dosed once a day (100, 200 and 400 mg) combined with pegylated interferon plus ribavirin for 28 days produced 4 week RVRs of 88 to 94% compared to 21% in the pegylated interferon plus ribavirin group (without PSI-7977). AT week 12 the cEVR (complete early virological response) was highest in the 200 mg QD (94%) and 400 (87%) compared to 64% cEVR in the pegylated interferon plus ribavirin (placebo) group. Based on these results a 12 week study is being planned. In addition PSI-7977 appears to work against different genotypes.
Post-conference highlights: RG7128 (500 or 1000 mg - BID) combined with pegylated interferon plus ribavirin was given in different doses and time lines based on response and it was found that RG7128 was safe and well-tolerated in HCV genotype 1 and 4 treatment-naïve patients with and without cirrhosis. The group that received the 8 or the 12 week regime of 1000 mg BID achieved the highest declines in HCV RNA (viral load) levels. RG7128 appears to have a high barrier to drug resistance.
Post-conference highlights: Telaprevir – see HCSP Fact Sheet.
Post-conference highlights: Interim results for a study of TMC435 (75 and 150 mg QD) combined with pegylated interferon plus ribavirin given for up to 24 weeks produced significant viral load reductions. In patients who completed 24 weeks treatment or stopped treatment for any reason by week 24 the SVR results ranged from 88 to 97% (119 out of 130 patients). So far there is a low rate of viral breakthrough.