Data from Viral Kinetic Study Showed Rapid Reduction of HCV RNA with ALS-2200 (VX-135), Vertex's Oral Nucleotide Analogue in Development for the Treatment of Hepatitis C
BOSTON --(Business Wire)--
Vertex (News - Alert) Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that data on ALS-2200 (VX-135), an oral medicine Vertex is developing for the treatment of hepatitis C, are being presented for the first time at The Liver Meeting®, the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
There was a median 4.54 log10 reduction (range -3.81, -5.08) in hepatitis C virus (HCV) RNA after seven days of dosing with ALS-2200 (200 mg) once daily in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Similar reductions in HCV RNA were seen in a seven-day viral kinetic study of once daily ALS-2200 (200 mg) in combination with ribavirin (n=8). ALS-2200 was well-tolerated in this study, with no serious adverse events and no discontinuations due to adverse events.
Based on these data, and to further characterize the medicine's safety and efficacy profile, Vertex plans to begin multiple Phase 2 studies of 12-week all-oral regimens in people with genotype 1 hepatitis C in early 2013, pending discussions with regulatory authorities. These studies will include combinations of VX-135 with GSK2336805 and separately with simeprevir (TMC435). Upon the start of Phase 2 studies, ALS-2200 will be known as VX-135. Screening in the first study, which will evaluate VX-135 in combination with ribavirin, is expected to begin in the coming weeks.
"We're working quickly to evaluate multiple all-oral treatment regimens with VX-135 and expect to have a significant amount of data from several Phase 2 studies by the end of 2013," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "Our goal is to proceed to pivotal development with one or more regimens that have the greatest potential to offer doctors and the people they treat a more tolerable, short-duration therapy with high viral cure rates for hepatitis C."
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 log10 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 #1882
November 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 (ß or ?) 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."
VX-135 Phase 2 Trials
Vertex recently announced that it has entered into two non-exclusive agreements to conduct Phase 2 proof-of-concept studies of VX-135 in combination with simeprevir (TMC435), a protease inhibitor being jointly developed by Janssen R&D Ireland and Medivir AB, and with GSK2336805, an NS5A inhibitor in development by GlaxoSmithKline (GSK). The studies with GSK2336805 and simeprevir are expected to begin in early 2013, pending discussions with regulatory authorities. Screening is expected to begin in the coming weeks for a Phase 2 study of VX-135 and ribavirin. Vertex also plans to begin a study of VX-135 and telaprevir, the company's approved protease inhibitor marketed as INCIVEK®(telaprevir) tablets for people with chronic genotype 1 hepatitis C, in early 2013, pending discussions with regulatory authorities. All of these Phase 2 studies will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment) using 12-week combination regimens.
About VX-135 (ALS-2200)
VX-135 (ALS-2200) is a uridine nucleotide analogue pro-drug that appears to have a high barrier to drug resistance based on in vitro studies. It is designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In vitro studies of the compound showed antiviral activity across all genotype, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.
Vertex gained worldwide rights to ALS-2200 through an exclusive worldwide licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that focuses on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.
About INCIVEK
INCIVEK® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK has been prescribed to more than 50,000 patients in the United States. Approximately three out of four U.S. patients who are prescribed a direct-acting antiviral for the treatment of genotype 1 chronic hepatitis C (HCV) receive INCIVEK combination therapy.
In Phase 3 clinical studies, 79 percent of people who had not previously been treated for HCV achieved a viral cure following treatment with INCIVEK combination therapy, compared with 46 percent of those who received pegylated-interferon and ribavirin (P/R) alone. Among people who were treated previously but did not achieve a viral cure, in the Phase 3 studies: 86 percent of relapsers achieved a viral cure with INCIVEK combination therapy compared to 22 percent with P/R alone; 59 percent of partial responders achieved a viral cure compared with 15 percent with P/R alone; and 32 percent of null responders achieved a viral cure compared with 5 percent with P/R alone. In addition, many people are eligible to complete treatment with INCIVEK combination therapy in 24 weeks - half the time required for P/R alone.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for adults with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).
Vertex developed telaprevir in collaboration with Janssen and Mitsubishi (News - Alert) Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic®.
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