Mass. -- October 25, 2010 -- Vertex Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced the initiation of a Phase 3b
study called OPTIMIZE that will evaluate twice-daily (BID) dosing
of a telaprevir-based combination regimen in people chronically
infected with genotype 1 hepatitis C virus (HCV) who have not
been treated previously. This is the first Phase 3 study to
evaluate twice-daily dosing of a protease inhibitor for the
treatment of hepatitis C. OPTIMIZE will not include a control
arm of pegylated-interferon and ribavirin alone.
"The sustained viral response rates, or viral cures, seen
across a broad range of people in the Phase 3 studies of telaprevir
set a high bar in the development of treatments for hepatitis
C, and we are committed to studying new ways to further improve
treatment," said Robert Kauffman, MD, PhD, Senior Vice
President and Chief Medical Officer for Vertex. "High viral
cure rates were demonstrated in the Phase 2 study of twice-daily
telaprevir and we're looking forward to conducting a larger
study to confirm these findings."
The OPTIMIZE study will be conducted by Vertex's collaborator,
In Vertex's recently completed Phase 3 registration program,
patients who received telaprevir in combination with pegylated-interferon
and ribavirin took telaprevir three times daily (750 mg; every
eight hours). OPTIMIZE is a randomized, open-label, Phase 3b
study that will evaluate twice-daily dosing (BID) of telaprevir
in people chronically infected with genotype 1 HCV who have
not been treated previously. The study will be conducted globally
at 135 clinical trial sites and enroll approximately 700 people.
Patient screening for enrollment in the OPTIMIZE study is expected
to start in November 2010.
For the first 12 weeks of the study, all patients will receive
2,250 mg of telaprevir taken twice daily (1,125 mg; BID) or
three times daily (750 mg; every eight hours) in combination
with pegylated-interferon alpha-2a (Pegasys) and twice-daily
ribavirin. Response guided therapy will be used to determine
whether patients receive pegylated-interferon and ribavirin
alone for an additional 12 weeks (24 weeks total) or 36 weeks
(48 weeks total) based on their treatment response at week 4.
The primary endpoint of the OPTIMIZE study is sustained viral
response (SVR) 24 weeks after the end of all treatment. The
primary objective is to demonstrate non-inferiority of BID telaprevir
versus telaprevir dosed every eight hours as measured by SVR.
SVR data from the study are expected as early as 2012. If these
data are positive, they may support the submission of a supplemental
New Drug Application (sNDA) for twice-daily (BID) dosing of
2 C208 study
Study C208 was an exploratory, four-arm, randomized, open label,
Phase 2 clinical trial that was conducted by Tibotec in Europe
in 161 treatment-naive patients with genotype 1 HCV infection.
The objective of Study C208 was to explore the safety, efficacy,
tolerability and pharmacokinetics of telaprevir administered
every 12 hours (1,125 mg) or every eight hours (750 mg). Each
dosing regimen of telaprevir was studied in combination with
either Pegasys or PegIntron and ribavirin, the currently approved
therapies for chronic HCV infection.
Across the four arms, SVR rates were 82% and 83% in patients
treated with telaprevir-based regimens every 12 hours (PegIntron
and Pegasys, respectively) and 81% and 85% in patients treated
with the every 8-hour regimen (PegIntron and Pegasys, respectively).
The primary endpoint was SVR, and data from this study were
presented at the 2009 annual meeting of the American Association
for the Study of Liver Diseases (AASLD). The Phase 2 C208 data
supported the initiation of the Phase 3b OPTIMIZE study.
In the C208 study, the frequency and severity of adverse events
(AEs) and the rate of treatment discontinuations were similar
to those reported in prior telaprevir trials. The rates of viral
breakthrough were similar to the every 8- and every 12-hour
regimens. The most common adverse events reported in patients
in Study C208 were pruritis, nausea, rash, anemia, flu-like
illness, fatigue and headache, and were similar overall between
the patient groups receiving every 8-hour dosing and those receiving
every 12-hour dosing.
Updates on the status of clinical trials of telaprevir are available
online at www.clinicaltrials.gov.
the Telaprevir Development Program
To date, more than 2,500 people with hepatitis C have received
telaprevir-based therapy as part of Phase 2 studies and the
Phase 3 ADVANCE, ILLUMINATE, and REALIZE studies. Together,
these studies enrolled people with genotype 1 hepatitis C who
had not been treated for their disease previously (ADVANCE and
ILLUMINATE) as well as people who had been treated before but
did not achieve a viral cure (REALIZE). A fact sheet on the
Phase 3 Telaprevir Development Program is available at www.vrtx.com/aasld2010.html.
Phase 3 ADVANCE
The pivotal Phase 3 ADVANCE study evaluated telaprevir-based
response-guided regimens in 1,095 treatment-naive patients.
The primary endpoint of ADVANCE was SVR, defined as the proportion
of people who had undetectable HCV RNA both at the end of treatment
and 24 weeks after the end of treatment. The secondary endpoint
was to evaluate the safety of telaprevir when dosed in combination
with pegylated-interferon and ribavirin. As part of a response-guided
design, people in the telaprevir-based treatment arms who had
undetectable HCV RNA (< 25 IU/mL, and undetectable by Roche
COBAS Taqman HCV test) at weeks 4 and 12 of treatment were eligible
to receive a total of 24 weeks of therapy. Patients who did
not meet the response-guided criterion but were undetectable
at week 24, received 48 weeks of total therapy.
Phase 3 ILLUMINATE Trial
The ILLUMINATE trial was a supplemental, open-label, Phase 3
study designed to evaluate whether there was any benefit in
extending therapy from 24 to 48 weeks in people whose hepatitis
C was undetectable (< 25 IU/mL undetectable) at weeks 4 and
12 of therapy. The primary endpoint of the study was the proportion
of people who achieved SVR in the randomized treatment groups,
and evaluated by a non-inferiority analysis.
Phase 3 REALIZE
REALIZE was the second Phase 3 pivotal trial designed to evaluate
telaprevir-based regimens in people who had received pegylated-interferon
based therapy but did not achieve a cure. REALIZE was the only
Phase 3 clinical trial to date of an investigational direct-acting
antiviral (DAA) to include all major subgroups of difficult-to-treat
patients including null responders, defined as people who had
a less than 2 log10 reduction in viral load by week 12 of a
prior course of therapy.
Vertex retains commercial rights to telaprevir in North America.
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.
Vertex 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 major pharmaceutical companies. Vertex's product pipeline
is focused on viral diseases, cystic fibrosis, inflammation,
autoimmune diseases, epilepsy, cancer and pain.
Vertex Pharmaceuticals. Vertex Pharmaceuticals Announces Start
of a Phase 3b Study of Twice-Daily Telaprevir in People Not
Treated Previously for Hepatitis C. Press release. October 25,