Seven-day viral kinetic data showed that when once-daily ALS-2200 (200 mg) was dosed in combination with ribavirin, there was a median 4.18 log 10 reduction (range -3.6, -5.2) in HCV RNA in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Five patients achieved HCV RNA levels below the limit of quantification (< LOQ = < 25 IU/mL), and two of these five achieved HCV RNA levels below the limit of detection (Roche COBAS Taqman HCV test, Version 2) after seven days of dosing. Similar to the data from the monotherapy cohort, ALS-2200 in combination with ribavirin was well-tolerated, no patients discontinued due to adverse events and there were no serious adverse events.
“The early antiviral activity and tolerability of this nucleotide analogue are very promising as we seek to develop new interferon-free treatment regimens,” said Patrick Marcellin, M.D., Ph.D., Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. “The data suggest VX-135 could be a core component of all-oral regimens for the treatment of hepatitis C.”
“Preclinical characterization of ALS-2200, a potent nucleotide polymerase inhibitor for the treatment of chronic hepatitis C.”
Poster presentation #1882November 13, 2012, 8:00 a.m. – 12:00 p.m. EST Preclinical data on ALS-2200 will be presented at AASLD that support the Phase 1 viral kinetic study and further clinical development plans. In preclinical studies, ALS-2200 was shown to be a potent, selective, specific, and pan-genotypic nucleotide analogue that inhibits the HCV NS5B polymerase. Specifically, there was no in vitro inhibition of non-HCV viruses, human DNA (β or γ) or RNA (II) polymerases, or mitochondrial protein synthesis. The studies also showed that ALS-2200 retains potency in vitro against a panel of HCV variants resistant to NS3/4A, NS5A and non-nucleoside NS5B inhibitors. “Analysis of ALS-2200, a novel potent nucleotide analog, combination drug interactions in the hepatitis C virus (HCV) subgenomic replicon system.” Poster presentation #1887 November 13, 2012, 8:00 a.m. – 12:00 p.m. EST Combination studies with ALS-2200 were performed in vitro to determine whether interactions with other drugs were additive, synergistic or antagonistic. Combination of ALS-2200 with either telaprevir or VX-222 demonstrated a synergistic effect, and combination with ribavirin resulted in an additive response. No significant cytotoxicity or antagonism were observed at any concentration of the combinations tested. Combinations of ALS-2200 and 18 other compounds were also tested, including simeprevir, which showed significant synergy with ALS-2200. “We’re pleased with the strength of our collaboration with Vertex and how it may lead to advances in the treatment of hepatitis C,” said Lawrence M. Blatt, Ph.D., Founder, President and Chief Executive Officer of Alios BioPharma. “We’re looking forward to seeing the results of several studies evaluating various all-oral combinations including VX-135.”