MA -- November 23, 2010 -- Vertex Pharmaceuticals Incorporated
(Nasdaq: VRTX) announced today that it has completed the submission
of a New Drug Application (NDA) to the U.S. Food and Drug Administration
(FDA) seeking approval for telaprevir, Vertex's investigational
treatment for people with hepatitis C. The NDA submission is
supported by results from three Phase 3 studies, ADVANCE, ILLUMINATE
and REALIZE, which evaluated telaprevir in people chronically
infected with genotype 1 hepatitis C virus (HCV) who were new
to treatment as well as those who were treated before but did
not achieve a sustained viral response (SVR, or viral cure).
The submission includes a request for Priority Review, which
would reduce the FDA's review time from 10 months to six months.
The FDA grants Priority Review status for several reasons, including
if the medicine is considered a major advance in treatment.
"This submission is a milestone in our more than 15-year
effort to change the way hepatitis C is treated," said
Matthew Emmens, Chairman, President and Chief Executive Officer
of Vertex. "We are committed to working closely with the
FDA to make telaprevir available as quickly as possible to the
millions of people with hepatitis C who need new medicines to
increase their chances for a viral cure."
Highlights of the Telaprevir Phase
3 Data Included in the Submission
All Phase 3 studies met their primary endpoints and results
below are from the treatment arms where telaprevir was started
immediately in combination with pegylated-interferon and ribavirin
for the first 12 weeks of treatment.
In people with hepatitis C who were new to treatment (treatment-naive):
to 75% achieved a viral cure with telaprevir-based combination
therapy, compared to 44% of people who received pegyalted
interferon and ribavirin alone;
majority (58% in ADVANCE and 65% in ILLUMINATE) were eligible
to reduce their treatment time by half -- from 48 weeks
to 24 weeks;
showed there was no benefit to extending total treatment
from 24 weeks to 48 weeks in people whose virus was undetectable
at weeks 4 and 12 with telaprevir-based therapy.
the three major subgroups of people with hepatitis C who had
not achieved a viral cure with a prior course of treatment (treatment-experienced):
of prior relapsers, 59% of prior partial responders and
29% of prior null responders achieved a viral cure with
telaprevir-based combination therapy compared to 24%, 15%,
and 5% of people in these subgroups, respectively, who received
pegyalted interferon and ribavirin alone. These results
were achieved with a simultaneous start of all three drugs
for the first 12 weeks followed by pegyalted interferon
and ribavirin alone for an additional 36 weeks.
safety and tolerability results of telaprevir-based combination
therapy were consistent across the Phase 3 studies. The most
common adverse events regardless of treatment arm were rash,
fatigue, pruritis, headache, nausea, anemia, insomnia, diarrhea,
flu-like symptoms and pyrexia, with the majority being mild
or moderate in severity.
More Effective Therapies Needed to
Improve Viral Cure Rates
Hepatitis C is a serious disease, typically without symptoms,
which affects up to 3.9 million people in the United States.
Hepatitis C can lead to scarring of the liver (cirrhosis), resulting
in liver failure, liver cancer and the need for liver transplantation.
Approved medicines for people with genotype 1 hepatitis C are
given for a year, and less than half of people treated with
these therapies achieve a viral cure. Telaprevir is an investigational,
oral inhibitor that acts directly on the HCV protease, an enzyme
essential for viral replication. To date, more than 2,500 people
with genotype 1 hepatitis C have received telaprevir in Phase
2 and Phase 3 studies.
"In our trials, starting patients with 12 weeks of telaprevir-based
combination therapy significantly improved viral cure rates
compared to treatment with currently approved medicines, even
in groups of people considered the most difficult to treat,"
said Peter Mueller, PhD, Chief Scientific Officer and Executive
Vice President of Global Research and Development at Vertex.
"We're also encouraged by telaprevir data that showed most
patients new to therapy were able to achieve high viral cure
rates and reduce their total treatment time by half."
Vertex is developing telaprevir in collaboration with Tibotec
Pharmaceuticals and Mitsubishi Tanabe Pharma. Vertex has rights
to commercialize telaprevir in North America and Tibotec has
rights 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 was granted Fast Track designation by the FDA for telaprevir
in 2005. In mid-2010, as part of the Fast Track designation,
Vertex began to submit completed sections of the NDA for review
by the FDA on a rolling basis rather than wait until every section
of the application was complete.
Data from Phase 3 Studies in All Major
Patient Types, Including the Most Difficult-to-Treat
The Phase 3 studies evaluated people with genotype 1 hepatitis
C who were new to treatment as well as those who had previously
received treatment but did not achieve a cure, including people
who have traditionally responded poorly to approved medicines.
In Phase 3 studies, telaprevir was given to people three times
a day in combination with pegylated-interferon and ribavirin
for the first 12 weeks of therapy followed by either 12 weeks
or 36 weeks of Pegasys (pegyalted interferon alfa-2a) and Copegus
(ribavirin) alone for a total treatment time of either 24 weeks
or 48 weeks. The ability to shorten treatment time from 48 weeks
to 24 weeks for people new to treatment was based on their response
to therapy at weeks 4 and 12. People who did not achieve a viral
cure with a prior course of therapy received a total of 48 weeks
of treatment. In October 2010, Vertex announced the start of
a Phase 3 study to evaluate twice-daily (BID) dosing of a telaprevir-based
ADVANCE: Pivotal study in 1,095 people who were
new to treatment
The primary endpoint of ADVANCE was SVR, defined as the proportion
of people who had undetectable viral load (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 pegyalted interferon and ribavirin.
ADVANCE also evaluated the ability to reduce total treatment
time by half -- from 48 weeks to 24 weeks, which was guided
by a patient's response to therapy (undetectable viral load
at weeks 4 and 12).
study in 540 people to evaluate shorter treatment durations
in people who were new to treatment
The primary endpoint of the study was SVR in two telaprevir-based
treatment arms of people whose virus was undetectable at week
4 and week 12 of treatment (eRVR, extended rapid viral response).
These patients were randomized to either 24 weeks or 48 weeks
of total therapy. ILLUMINATE was designed to evaluate whether
there was any benefit to extending therapy from 24 weeks to
48 weeks in people who met these criteria. There was no control
arm of pegyalted interferon and ribavirin alone in the study.
In both the ADVANCE and ILLUMINATE studies, telaprevir-based
combination therapy also resulted in improved SVR rates in various
subgroups of people with characteristics known to limit response
to approved medicines such as race/ethnicity or stage of liver
fibrosis. Data from these studies were presented in November
2010 at the 61st Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD).
REALIZE: Pivotal study
in 662 people who did not achieve a viral cure with previous
The primary endpoint of the study was SVR in each of the two
telaprevir treatment arms compared to the control arm, and for
the three subgroups of people included in the study. REALIZE
is the only Phase 3 study to date of a direct-acting antiviral
medicine to include all three major subgroups of people with
hepatitis C who did not achieve a viral cure with a previous
course of therapy:
defined as a person whose hepatitis C virus was undetectable
at the completion of at least 42 weeks of a prior course
of therapy but whose virus became detectable during the
Responder: defined as a person who achieved at least a 2
log10 (100 times) reduction in viral load (HCV RNA) at week
12, but whose hepatitis C virus never became undetectable
by week 24 of a prior course of therapy; and
Responder: defined as a person who experienced a less than
2 log10 drop in viral load at week 12 of a prior course
REALIZE, people received 48 weeks of total therapy, which included
12 weeks of telaprevir combined with pegyalted interferon and
ribavirin. One of the telaprevir treatment arms was designed
to evaluate, for the first time, whether viral cure rates could
be further improved by starting pegyalted interferon and ribavirin
alone for the first four weeks of treatment (delayed start)
compared to a simultaneous start of telaprevir in combination
with these medicines. There was no clinical benefit observed
with the telaprevir delayed-start treatment arm in any of the
subgroups of patients compared to the simultaneous-start arm.
Final results from REALIZE, including safety and efficacy data,
will be presented at an upcoming medical meeting.
Safety and Tolerability Information
for ADVANCE, ILLUMINATE and REALIZE
The safety and tolerability results of telaprevir-based combination
regimens were consistent across the Phase 3 studies. The most
common adverse events (AEs) were rash, fatigue, pruritis, headache,
nausea, anemia, insomnia, diarrhea, flu-like symptoms and pyrexia
with the majority being mild or moderate in severity. Rash and
anemia occurred more frequently in the telaprevir treatment
arms compared to the control arms.
Rash was primarily characterized as eczema-like, manageable
and resolved upon stopping telaprevir. More than 90% of rash
was mild to moderate and was primarily managed with the use
of topical corticosteroids and antihistamines. Anemia was primarily
managed by reducing the dose of ribavirin. Erythropoiesis-stimulating
agents (ESAs) were used in only 1% of people in the Phase 2
and Phase 3 studies. Discontinuation of all drugs due to either
rash or anemia during the telaprevir/placebo treatment phase
was 1% to 3% in the telaprevir treatment arms.
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 other pharmaceutical companies. Vertex's product pipeline
is focused on viral diseases, cystic fibrosis, inflammation,
autoimmune diseases, epilepsy, cancer and pain. For more information,
Vertex Pharmaceuticals. Vertex Completes New Drug Application
for Telaprevir for Hepatitis C. Press
release. Press release. November 23, 2010.