– 4.54 log10 median reduction in HCV RNA
observed in people with genotype 1 hepatitis C treated with a once-daily
200 mg dose of ALS-2200 for seven days; treatment was well-tolerated-
– Phase 2 studies of 12-week all-oral regimens planned for this year –
CAMBRIDGE, Mass.–(BUSINESS WIRE)–
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and its collaborator
Alios BioPharma, Inc. today announced positive results from a viral
kinetic study of the nucleotide analogue ALS-2200 for the treatment of
hepatitis C. There was a median 4.54 log10 reduction in
hepatitis C virus (HCV) RNA in people with genotype 1 chronic hepatitis
C who were new to treatment (n=8) after seven days of dosing with 200 mg
of ALS-2200 once daily. ALS-2200 was well-tolerated in this study, and
no patients discontinued due to adverse events. Based on these data,
Vertex plans to begin Phase 2 studies this year of 12-week all-oral
regimens including ALS-2200 in people with genotype 1 hepatitis C,
pending discussions with regulatory agencies.
Patients with hepatitis C dosed with ALS-2200 in this study had a
dose-dependent, consistent and rapid decline in HCV RNA. After three
days of dosing, a median 3.85 log10 decline was observed
among patients in the 200 mg dose group. In this dose group, a median
4.54 log10 decline was observed after seven days of dosing,
which was maintained for up to two days after the completion of dosing.
Four of eight patients in this dose group achieved HCV RNA levels below
the limit of quantification ( < LOQ = < 25 IU/mL). There were no serious
adverse events observed in people dosed with ALS-2200 in the study. Data
from this study have been submitted to a medical meeting for
presentation in the second half of this year.
Based on these data, Vertex expects to conduct a study to evaluate
ALS-2200 in combination with INCIVEK® (telaprevir),
the company’s approved protease inhibitor for people with genotype 1
hepatitis C, and a study of ALS-2200 in combination with ribavirin.
These studies will evaluate 12 total weeks of treatment with a primary
endpoint of SVR12 (sustained viral response: undetectable hepatitis C
virus 12 weeks after the end of treatment) in people with genotype 1
“We’re encouraged by the substantial, rapid and consistent viral decline
and initial safety results from this study, which make ALS-2200 a very
promising part of Vertex’s hepatitis C pipeline,” said Robert Kauffman,
M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex.
“ALS-2200, with its high level of antiviral activity, gives us
flexibility to explore several combinations of all-oral treatment
regimens for hepatitis C. We’re moving quickly to begin the first Phase
2 trials this year.”
Additional results from the study of ALS-2200 in people with hepatitis C
are included in the following table:
“The rapid advancement of ALS-2200 through this first viral kinetic
study underscores the strength of our collaboration with Vertex and our
shared commitment to develop new medicines for hepatitis C,” said
Lawrence M. Blatt, Ph.D., Founder, President and Chief Executive Officer
of Alios BioPharma. “We look forward to continued collaboration with
Vertex and to the start of multiple Phase 2 studies of ALS-2200 later
ALS-2200 Phase 1 Trial Design
This double-blind, placebo-controlled, Phase 1 trial was designed to
evaluate the safety and tolerability of single ascending doses of
ALS-2200 in healthy volunteers and of multiple ascending doses in people
with genotype 1 chronic hepatitis C. A secondary objective was to
evaluate the effects on viral kinetics of ALS-2200 during seven days of
dosing in people with hepatitis C. The first part of the trial enrolled
healthy volunteers to evaluate pharmacokinetics of single ascending
doses of ALS-2200. The second part of the study enrolled people with
hepatitis C to evaluate the antiviral activity of multiple ascending
doses of ALS-2200. Of the patients with hepatitis C in the ALS-2200
treatment groups, two were genotype 1a, 29 were genotype 1b and one
patient’s genotype 1 subtype was not able to be determined.
About ALS-2200 and ALS-2158
Vertex and Alios are also conducting a Phase 1 seven-day viral kinetic
study of a second nucleotide analogue, ALS-2158. Data from this study
are expected in the next few months.
ALS-2200 and ALS-2158 are nucleotide analogues that appear to have a
high barrier to drug resistance based on in vitro studies. Both
compounds are designed to inhibit the replication of the hepatitis C
virus by acting on the NS5B polymerase. Each compound is structurally
distinct (adenosine and uridine) and has a different mechanism of
action. In vitro studies of both compounds showed
antiviral activity across all genotypes, or forms, of the hepatitis C
virus, including genotypes more prevalent outside of the United States.
Vertex gained worldwide rights to ALS-2200 and ALS-2158 through an
exclusive worldwide licensing agreement signed with Alios BioPharma,
Inc. in June 2011. The agreement also includes a research program that
will focus 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.
INCIVEK® (telaprevir) tablets is an oral medicine that
acts directly on the hepatitis C virus protease, an enzyme essential for
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
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®.
IMPORTANT SAFETY INFORMATION
Read more here