Combo Works for HCV Patients with Prior Unsuccessful Treatment
The REALIZE study showed that adding telaprevir to standard
hepatitis C therapy increased sustained response rates for
people with previous unsuccessful treatment attempts, researchers
reported this week at EASL 2011.
lead investigational hepatitis C virus (HCV) protease inhibitor,
is currently undergoing review by the U.S. Food and Drug Administration
(FDA), along with Merck's protease inhibitor boceprevir.
anti-HCV drugs will bring about a new paradigm in treatment
for chronic hepatitis C, especially
for hard-to-treat patients with HCV genotype 1 who did not achieve
a sustained virological response (SVR), or cure, with a prior
course of standard therapy consisting of pegylated
interferon plus ribavirin.
the European Association for the Study of the Liver's International
Liver Congress (EASL 2011) this week
in Berlin, researchers presented final results from a Phase
3 study of telaprevir plus pegylated interferon/ribavirin in
treatment-experienced patients, including "null responders"
who showed little or no decrease in HCV viral load, partial
responders, and relapsers who experienced initial viral suppression
but their HCV bounced back after the end of therapy.
is an edited excerpt from a press release issued by telaprevir
developer Vertex describe the REALIZE study and its findings.
Results From Phase 3 REALIZE Study
Showed Telaprevir-Based Therapy Significantly Improved SVR (Viral
Cure) Rates in People Whose Prior Treatment For Hepatitis C
major subgroups achieved significantly higher viral cure
rates with telaprevir-based therapy compared to pegylated
interferon and ribavirin: 86% vs. 24% in prior relapsers,
57% vs. 15% in prior partial responders and 31% vs. 5% in
prior null responders.
clinical benefit was observed in delaying telaprevir therapy
by four weeks (lead-in) compared to starting telaprevir,
pegylated-interferon and ribavirin simultaneously.
Safety and tolerability results were consistent with prior
Phase 3 studies of telaprevir.
-- March 31, 2011 -- Vertex Pharmaceuticals Incorporated (Nasdaq:
VRTX) today announced final results from its pivotal Phase 3
REALIZE study that evaluated people with genotype 1 chronic
hepatitis C whose prior treatment with pegylated-interferon
and ribavirin was unsuccessful either because they relapsed,
had a partial response or had a null response. Data from the
study showed that people in each of these subgroups who were
treated with telaprevir-based combination therapy achieved superior
rates of sustained viral response (SVR, or viral cure) compared
to those treated with pegylated interferon and ribavirin alone.
REALIZE also evaluated whether viral cure rates could be further
improved by delaying the start of telaprevir by four weeks,
during which time patients received four weeks of pegylated-interferon
and ribavirin alone (lead-in), compared to a simultaneous start.
The data showed no clinical benefit to a lead-in for people
treated with telaprevir-based combination therapy. Safety and
tolerability results were consistent with results from the prior
Phase 3 studies of telaprevir. These data were presented today
at The International Liver Congress 2011, 46th annual meeting
of the European Association for the Study of the Liver (EASL)
in Berlin, Germany. REALIZE was conducted by Vertex's collaborator,
"Patients with chronic hepatitis C who undergo re-treatment
with currently available medicines rarely achieve a viral cure
and remain at an increased risk for advancing to more serious
liver disease," said Stefan Zeuzem, MD, Professor of Medicine
and Chief of the Department of Medicine at the JW Goethe University
Hospital, Frankfurt, Germany and principal investigator for
REALIZE. "These data are important because they showed
that viral cure rates were three to six times higher for patients
treated with a telaprevir-based regimen compared to re-treatment
with currently available medicines."
Among those in the simultaneous start arm of REALIZE, 83 percent
(121/145) of prior relapsers, 59 percent (29/49) of prior partial
responders and 29 percent (21/72) of null responders achieved
viral cures compared to 24 percent (16/68), 15 percent (4/27)
and 5 percent (2/37), respectively, who received pegylated interferon
and ribavirin. The viral cure rates among those in the lead-in
arm were 88 percent (124/141) among prior relapsers, 54 percent
(26/48) among prior partial responders and 33 percent (25/75)
among prior null responders. In a combined endpoint analysis
of the two telaprevir-based treatment arms, 86 percent (245/286)
of prior relapsers, 57 percent (55/97) of prior partial responders
and 31 percent (46/147) of prior null responders achieved viral
"The REALIZE results are encouraging, especially considering
people in this study had been unsuccessfully treated in the
past and many already had scarring of the liver," said
Robert Kauffman, MD, PhD, Senior Vice President and Chief Medical
Officer for Vertex. "Rates of viral cure among those treated
with telaprevir-based regimens were similar between the simultaneous
and delayed start arms of the study, supporting the conclusion
that there was no clinical benefit to a lead-in strategy with
In this study, 48 percent (316/662) of patients overall had
advanced liver fibrosis or cirrhosis (scarring of the liver)
and 89 percent (586/662) of patients overall had high amounts
of hepatitis C virus (high viral load; HCV RNA ? 800,000 IU/mL)
upon study entry.
of REALIZE Results
REALIZE is the only Phase 3 hepatitis C study to date of a direct-acting
antiviral medicine in development that was designed to evaluate
people whose prior treatment was unsuccessful, including those
who had a null response. [Editor's note: Merck's RESPOND-2
study tested boceprevir in prior non-responders and relapsers.]
In this study, patients were randomized 2:2:1 to two telaprevir-based
treatment arms (simultaneous or lead-in) or a control arm of
48 weeks of pegylated interferon and ribavirin alone. Patients
in the telaprevir treatment arms received a total of 12 weeks
of telaprevir-based combination therapy. In the lead-in arm,
patients received four weeks of pegylated interferon and ribavirin
followed by telaprevir in combination with pegylated interferon
and ribavirin for 12 weeks followed by 32 weeks of pegylated
interferon and ribavirin alone. For those in the simultaneous
start arm, the telaprevir-based combination was followed by
an additional 36 weeks of pegylated-interferon and ribavirin
alone. The primary endpoint of the REALIZE study was SVR in
each of the two telaprevir treatment arms compared to the control
arm and for the three groups of people included in the study.
The total treatment time for all patients in REALIZE was 48
Results % (n)
Simultaneous Start Arm+
= telaprevir; q8h = every 8 hours]
SVR rates observed were statistically significant when
compared with the control arm (p <0.001).
+Simultaneous start: 12 weeks of telaprevir (750 mg, q8h),
Pegasys (PEG, pegylated-interferon alfa-2a) & Copegus
(RBV, ribavirin), followed by 36 weeks of PEG & RBV
++Lead-in: 4 weeks of PEG & RBV alone followed by
12 weeks of telaprevir (750 mg, q8h), PEG & RBV, followed
by 32 weeks of PEG & RBV alone. There was no clinical
benefit with the use of a four-week lead in with no significant
improvement in SVR rates and no significant reduction
in virologic failure and relapse rates in the lead-in
start arm compared to the simultaneous start arm.
+++Control: 12 weeks of placebo, PEG & RBV, followed
by 36 weeks of Peg & RBV alone.
Relapser: 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 follow-up period.
Prior Partial Responder: Defined as a person who achieved
at least a 2 log10 reduction in HCV RNA at week 12, but
whose hepatitis C virus never became undetectable by week
24 of a prior course of therapy.
Prior Null Responder: Defined as a person who achieved a
less than 2 log10 reduction in HCV RNA at week 12 of a prior
course of therapy.
and Tolerability Information for the Phase 3 Studies of Telaprevir
The safety and tolerability results of the telaprevir-based
combination regimens were consistent across the Phase 3 studies.
The most common adverse events were fatigue, pruritis [itching],
nausea, headache, rash, anemia, flu-like symptoms, insomnia
and diarrhea with the majority being mild to moderate. Rash
and anemia occurred more frequently in the telaprevir-based
treatment arms compared to the control group.
Rash was primarily characterized as eczema-like, manageable
and resolved upon stopping telaprevir. More than 90 percent
of rash was mild to moderate and primarily managed with the
use of topical corticosteroids and/or antihistamines. Anemia
was primarily managed by reducing the dose of ribavirin.
To optimize each patient's opportunity to achieve viral cure
in the Phase 3 studies, sequential discontinuation of the medicines
was recommended as a strategy to manage certain adverse events.
This strategy allowed patients to continue on pegylated-interferon
and ribavirin after stopping telaprevir. Discontinuation of
all medicines due to either rash or anemia during the telaprevir/placebo
treatment phase was 1 percent to 3 percent in the telaprevir
About the Study
REALIZE was a pivotal Phase 3, randomized, double-blind, placebo-controlled,
global study. The majority of clinical trial sites were in Europe.
The study was designed to evaluate the efficacy, safety and
tolerability of telaprevir-based combination regimens in people
infected with genotype 1 chronic hepatitis C who did not achieve
a viral cure after at least one course of prior treatment with
Status of Telaprevir Regulatory Applications
The regulatory applications for the approval of telaprevir have
been granted Priority Review by the U.S. Food and Drug Administration
(FDA) and Health Canada and accelerated assessment by the European
Medicines Agency for the treatment of people with genotype 1
chronic hepatitis C. The FDA has scheduled its Antiviral Drugs
Advisory Committee to discuss the New Drug Application for telaprevir
on April 28, 2011. A target response date of May 23, 2011 is
set under the Prescription Drug User Fee Act (PDUFA). The applications
include data from three registration studies, ADVANCE, ILLUMINATE
and REALIZE, which evaluated telaprevir in combination with
pegylated-interferon and ribavirin in people with hepatitis
C who were new to treatment as well as those who did not achieve
a viral cure after treatment with currently available medicines.
For complete information on the telaprevir clinical trials or
a fact sheet on the trial designs visit: www.vrtx.com/press.cfm.
About the Telaprevir Development Program
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 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 chronic hepatitis C
who had not been treated for their disease previously as well
as people who had been treated before but did not achieve a
Vertex is developing telaprevir 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.
creates new possibilities in medicine. Our team aims to discover,
develop and commercialize 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, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have
ongoing worldwide research programs and sites in the U.S., U.K.
For more information and to view Vertex's press releases, please
Pharmaceuticals. Results From Phase 3 REALIZE Study Showed Telaprevir-Based
Therapy Significantly Improved SVR (Viral Cure) Rates in People
Whose Prior Treatment For Hepatitis C Was Unsuccessful. Press
release. March 31, 2011.