- 4.54 log10 median reduction in HCV RNA after 7 days of dosing; ALS-2200 was well-tolerated with no serious adverse events and no discontinuations due to adverse events -
- Vertex moving forward with multiple Phase 2 trials in early 2013 exploring all-oral combinations, including VX-135 with GSK2336805 and with simeprevir (TMC435) -
"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
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
"Preclinical characterization of ALS-2200, a potent nucleotide polymerase inhibitor for the treatment of chronic hepatitis C."
Poster presentation #1882
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
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
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
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 genotypes, or forms, of
the hepatitis C virus, including genotypes more prevalent outside of
Vertex gained worldwide rights to ALS-2200 through an exclusive
worldwide licensing agreement signed with
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
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
Vertex developed telaprevir in collaboration with Janssen and Mitsubishi
Tanabe Pharma. Vertex has rights to commercialize telaprevir in
IMPORTANT SAFETY INFORMATION
INCIVEK® (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1 Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.3,4
More than 170 million people worldwide are chronically infected with
hepatitis C.5 In
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.
Founded more than 20 years ago in
Vertex's press releases are available at www.vrtx.com.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including, without
limitation, the statements of Dr. Kauffman, Dr. Marcellin and Dr. Blatt
and statements about Vertex's expectations regarding the timing and
structure of multiple Phase 2 studies exploring all-oral treatment
regimens that include VX-135 in combination with GSK2336805, TMC435,
ribavirin or INCIVEK. While the company believes the forward-looking
statements contained in this press release are accurate, there are a
number of factors that could cause actual events or results to differ
materially from those indicated by such forward-looking statements.
Those risks and uncertainties include, among other things, that the
initiation of Phase 2 studies of VX-135 may be delayed or prevented,
outcomes from any future studies of VX-135 may not be favorable and the
other risks listed under Risk Factors in Vertex's annual report and
quarterly reports filed with the
2 Pearlman BL and
3 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
4 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
6 Chak, E, et. al.
8 Smith, BD, et al. Hepatitis C Virus Antibody Prevalence,
Correlates and Predictors among Persons Born from 1945 through 1965,
9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact
of antiviral therapy for hepatitis C in
10 Ly KN, et al. The Increasing Burden of Mortality From
Viral Hepatitis in
11 Pyenson B, Fitch K, and
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