agents that interfere with the HCV lifecycle promise to revolutionize
treatment of chronic hepatitis C. Most studies of these drug
candidates so far have combined them with standard therapy consisting
of pegylated interferon
(Pegasys or PegIntron) plus ribavirin, producing higher
sustained response rates with shorter courses of treatment.
these new HCV drugs will initially be used in combination with
pegylated interferon, researchers have begun testing combinations
of direct-acting agents that target different steps of the
viral lifecycle, for example a protease inhibitor plus a polymerase
inhibitor -- resembling combination antiretroviral therapy for
HIV. Some recent studies have combined targeted agents with
just ribavirin, creating all-oral regimens that may reduce the
risk of relapse.
recently reported study data indicate that one such combination
-- 1125 mg telaprevir plus 400 mg VX-222 administered twice-daily
for 12 weeks -- was not as effective as regimens that also included
interferon and/or ribavirin, leading to greater likelihood of
viral breakthrough and therefore lower rates of sustained virological
is an edited excerpt from a Vertex press release describing
the trial modifications.
Provides Update to Ongoing Phase 2 Study Evaluating Combinations
of Telaprevir and VX-222 for the Treatment of Hepatitis C
Two-drug treatment arm of telaprevir and VX-222 alone discontinued.
- Study continues with three arms, including all-oral combination
of Vertex's lead protease and polymerase inhibitors with ribavirin.
- Both of the four-drug treatment arms are fully enrolled;
the majority of patients in these arms have reached 8 weeks
or more of treatment.
Mass. -- December 21, 2010 -- Vertex Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced a modification of its Phase 2
clinical trial evaluating 12-week, response-guided regimens
of its lead investigational hepatitis C virus (HCV) protease
inhibitor, telaprevir, in combination with its lead investigational
HCV polymerase inhibitor, VX-222. The company has discontinued
the second two-drug treatment arm of telaprevir and VX-222 alone
as a result of meeting a pre-defined stopping rule related to
viral breakthrough. This two-drug arm was designed to evaluate
a 12-week combination regimen of VX-222 (400 mg) and telaprevir
(1,125 mg) dosed twice daily without pegylated-interferon and
ribavirin. The first two-drug arm was discontinued in October
2010 and was designed to evaluate a 12-week combination regimen
of VX-222 (100 mg) and telaprevir (1,125 mg).
The study will continue as planned with three treatment arms.
Two of the treatment arms are fully enrolled and are evaluating
four-drug combinations of telaprevir (1,125 mg), VX-222 (400
mg or 100 mg), Pegasys (pegylated-interferon
alfa-2a) and Copegus (ribavirin). The last patient was randomized
and began treatment with a four-drug regimen in November 2010.
There are patients in the four-drug treatment arms who have
recently started treatment and have not yet reached week 8 of
therapy. More than half of patients in the treatment arms have
received eight weeks or more of treatment and approximately
one third of patients are in weeks 10 through 12 of treatment.
Some patients in this study have completed therapy. Interim
data from both of the four-drug treatment arms are expected
in the first quarter of 2011. In November 2010, Vertex announced
the planned addition of a new three-drug treatment arm designed
to evaluate the potential of an all-oral, interferon-free regimen
of telaprevir (1,125 mg), VX-222 (400 mg) and ribavirin dosed
twice daily. Enrollment in this new treatment arm is expected
to begin in the first quarter of 2011.
"This trial has provided important information regarding
telaprevir and VX-222-based combination regimens, and three
of the five treatment arms are proceeding as planned,"
said Robert Kauffman, MD, PhD, Senior Vice President and Chief
Medical Officer for Vertex. "We are pleased with the progress
of both four-drug treatment arms and look forward to the first
quarter of 2011 when on-treatment data from these arms will
become available and enrollment in the three-drug treatment
arm is expected to begin."
About the Ongoing Phase 2 Trial of Telaprevir and VX-222
In August 2010, patients enrolled in this randomized, parallel-group,
dose-ranging Phase 2 trial started receiving treatment. The
primary endpoint of this trial is to assess safety and tolerability
of 12-week, telaprevir/VX-222-based combination therapy in people
with genotype 1 chronic hepatitis C. A secondary endpoint of
this study is to assess on-treatment antiviral activity and
the proportion of patients in each study arm who achieve a sustained
viral response (SVR; defined as undetectable HCV RNA 24 weeks
after the end of treatment). Patients who meet the response-guided
criteria during treatment (undetectable HCV RNA at week 2 and
week 8 of treatment) stop all therapy at week 12.
The planned addition of the three-drug treatment arm to the
study took into account an initial review of adverse events
among people treated with telaprevir/VX-222 combination regimens
in this study. Enrollment in this new study arm is expected
to begin in the first quarter of 2011 pending completion of
institutional review board (IRB) approvals and consultations
with regulatory agencies. A sixth and final arm may be added
to the trial per protocol based on data from the study expected
in the first quarter of 2011.
European and United States Regulatory Submissions for Telaprevir
On December 17, 2010, Janssen-Cilag International NV announced
the submission of a Marketing Authorization Application (MAA)
to the European Medicines Agency (EMA) for telaprevir in combination
with pegylated-interferon and ribavirin for the treatment of
people with genotype 1 hepatitis C. Additionally, Janssen announced
that the EMA has accepted telaprevir for accelerated assessment,
which is granted to new medicines of major public health interest.
In November 2010, Vertex announced it has completed the submission
of a New Drug Application to the U.S. Food and Drug Administration
for telaprevir in combination with pegylated-interferon and
ribavirin for the treatment of people with genotype 1 hepatitis
C. The submission included a request for six-month Priority
Review, which can be granted for several reasons, including
if the medicine is considered a major advance in treatment.
Telaprevir is being developed by Vertex Pharmaceuticals in collaboration
with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights
to commercialize telaprevir in North America. Through its affiliate,
Janssen, Tibotec has rights to commercialize telaprevir in Europe,
South America, Australia, the Middle East and certain other
countries. Mitsubishi Tanabe Pharma has rights to commercialize
telaprevir in Japan and certain Far East countries.
About Telaprevir and VX-222
Telaprevir is an investigational, oral inhibitor of HCV protease,
an enzyme essential for viral replication. VX-222 is an investigational,
oral, non-nucleoside inhibitor of HCV NS5B polymerase. Vertex
added VX-222 to its development pipeline as part of the acquisition
of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide
commercial rights to VX-222.
Pharmaceuticals Incorporated is a global biotechnology company
committed to the discovery and development of breakthrough small
molecule drugs for serious diseases. The company's strategy
is to commercialize its products both independently and in collaboration
with other pharmaceutical companies. Vertex's product pipeline
is focused on viral diseases, cystic fibrosis, inflammation,
autoimmune diseases, epilepsy, cancer and pain. For more information,
Pharmaceuticals. Vertex Provides Update to Ongoing Phase 2 Study
Evaluating Combinations of Telaprevir and VX-222 for the Treatment
of Hepatitis C. Press release. December 21, 2010.