Combo with Telaprevir and VX-222 Clears
HCV at 12 Weeks
90% of previously untreated genotype 1 chronic hepatitis
C patients treated with telaprevir plus VX-222 plus pegylated
interferon and ribavirin achieved undetectable viral load
at week 12, researchers reported at EASL 2011.
is Vertex's lead investigational hepatitis C virus (HCV) protease
inhibitor, which is currently undergoing review by the U.S.
Food and Drug Administration (FDA). VX-222 is a non-nucleoside
HCV polymerase inhibitor.
presented 12-week results from the Phase 2 ZENITH trial at the
European Association for the Study of the Liver's International
Liver Congress (EASL 2011) this week
study initially compared telaprevir plus VX-222 alone vs these
2 drugs with standard therapy using pegylated
interferon alfa-2a (Pegasys) plus ribavirin. The all-oral
2-drug arms were halted early due to viral breakthrough. The
trial continued testing the 4-drug combo, and researchers also
added a 3-drug interferon-sparing regimen consisting of telaprevir,
VX-222, and ribavirin.
is an edited excerpt from a press release issued by Vertex describing
the ZENITH study and its preliminary findings.
Phase 2 Data Showed Rapid Viral Response to VX-222
in Combination with Telaprevir, Pegylated Interferon
and Ribavirin Among People With Hepatitis C
study to evaluate four-drug, 12-week treatment duration for
Berlin -- March 31, 2011 -- Vertex Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced interim results from an ongoing
Phase 2 study (ZENITH) designed to assess the safety and tolerability
of 12-week response-guided treatment regimens with its polymerase
inhibitor, VX-222, and its protease inhibitor, telaprevir, in
combination with pegylated interferon and ribavirin in people
with genotype 1 chronic hepatitis C who were new to treatment.
The study enrolled 106 people into one of four treatment groups.
Among those who received VX-222 (400 mg) in combination with
telaprevir, pegylated-interferon and ribavirin, interim data
showed that 90 percent (27/30) of them had undetectable hepatitis
C virus at week 12. Half (15/30) of those in the VX-222 (400
mg) treatment group were eligible to stop all treatment at week
12. People in this same treatment group who were not eligible
to stop all treatment at 12 weeks were assigned to receive 24
total weeks of treatment: 12 weeks of the four-drug regimen
followed by 12 weeks of pegylated-interferon and ribavirin alone.
Preliminary safety results showed that the most frequently reported
adverse events were mild gastrointestinal symptoms and mild
fatigue. At the time of this analysis, there were no discontinuations
due to gastrointestinal symptoms. Data from this study are being
presented today at The International Liver Congress 2011, the
46th annual meeting of the European Association for the Study
of the Liver (EASL) in Berlin, Germany.
"Telaprevir triple therapy demonstrated significant improvements
in viral cure rates and an ability to halve treatment time to
24 weeks for many people in late-stage studies," said Robert
Kauffman, MD, PhD, Senior Vice President and Chief Medical Officer
for Vertex. "Reducing treatment time in half again to 12
weeks would be another important advance and the early data
from this study provide new information about the potential
to do this with a four-drug VX-222 regimen."
Using an intent-to-treat analysis, 57 percent (17/30) of people
treated with VX-222 (400 mg) in combination with telaprevir,
pegylated interferon and ribavirin had undetectable hepatitis
C virus by week two. Among people who were treated with VX-222
(100 mg) in combination with telaprevir, pegylated interferon
and ribavirin, 38 percent (11/29) had undetectable hepatitis
C virus by week two.
To determine if patients were eligible to stop all treatment
at 12 weeks in ZENITH, they had to have undetectable hepatitis
C virus at weeks two and eight. Using the eligibility criteria
for a 12-week total treatment duration, half (15/30) of the
patients in the high-dose VX-222 combination group and 38 percent
(11/29) in the low-dose combination group were eligible to stop
all treatment at 12 weeks. Ninety percent (27/30) of patients
in the high-dose VX-222 group had undetectable hepatitis C virus
by week 12 as did 83 percent (24/29) in the low-dose VX-222
group. No viral breakthrough was observed through week 12 among
patients receiving the four-drug combinations.
"The early data from this study are encouraging because
they showed patients had a very rapid decline in hepatitis C
virus as early as the second week of treatment," said Adrian
Di Bisceglie, MD, Chief of Hepatology at Saint Louis University
School of Medicine. "Hepatitis C virus was undetectable
at week 12 of treatment in 90 percent of patients who received
the higher dose of VX-222, and half of those in this treatment
group were eligible to stop all treatment at that time."
ZENITH is an ongoing Phase 2 study that enrolled 106 people
and began with four treatment arms evaluating two-drug and four-drug
combination regimens. The primary endpoint is safety and tolerability
and the secondary endpoint is on-treatment antiviral activity
and the proportion of people in each treatment arm who achieve
a sustained viral response (SVR, defined as undetectable hepatitis
C virus 24 weeks after the end of treatment). The study is designed
to evaluate various combinations of VX-222, telaprevir, pegylated-interferon
and ribavirin for the treatment of genotype 1 chronic hepatitis
In this study, VX-222, telaprevir and ribavirin are given twice
daily. Arms A (n=18) and B (n=29) were designed to evaluate
the all-oral, two-drug combination regimens of VX-222 (400 mg
or 100 mg) and telaprevir (1,125 mg). Both of these study arms
were discontinued due to a pre-defined stopping rule related
to viral breakthrough. Arms C (n=29) and D (n=30) are ongoing
and designed to evaluate the four-drug combination regimens
of VX-222 (400 mg and 100 mg), telaprevir (1,125 mg), pegylated-interferon
An additional treatment arm has been added to the study to evaluate
an all-oral, three-drug regimen of VX-222, telaprevir and ribavirin
in people with genotype 1b chronic hepatitis C. This study arm
is now open for enrollment. A sixth and final arm may be added
to the trial per protocol based on data from the study.
Interim Intent to Treat (ITT) Analysis of Arms C and D
(100 mg) /TVR-
(400 mg) /TVR-based arm(++)
2 HCV RNA undetectable
2 and 8 HCV RNA undetectable*
4 HCV RNA undetectable (RVR)
12 HCV RNA undetectable (eRVR)
= telaprevir; BID = twice-daily]
HCV RNA was evaluated using the TaqMan assay version 2.0.
part of a response-guided regimen, people who have undetectable
hepatitis C virus at weeks 2 and 8 are eligible to stop
all treatment at week 12.
+VX-222 (100 mg, BID), telaprevir (1,125 mg, BID), Pegasys
(pegylated interferon alfa-2a) and Copegus (ribavirin).
++VX-222 (400 mg, BID), telaprevir (1,125 mg, BID), Pegasys
(pegylated-interferon alfa-2a) and Copegus (ribavirin).
Safety and Tolerability
The 12-week safety and tolerability results are preliminary
and include data on all patients enrolled in the study: those
enrolled in the two-drug (n=47) and four-drug (n=59) treatment
arms. The most frequent adverse events observed in this study
were mild gastrointestinal symptoms (including diarrhea, nausea
and vomiting) and mild fatigue. No patients discontinued due
to gastrointestinal symptoms.
Preliminary safety data indicate that there were six discontinuations
due to adverse events among the four treatment arms through
week 12. There were two serious adverse events considered by
the investigator to be potentially related to study medication:
acute renal failure (Arm B), which resolved after study medications
were discontinued and anemia (Arm C). There was one additional
severe adverse event reported of pneumonia, septic shock and
renal failure; this severe adverse event was considered by the
investigator to be unrelated to study medication. The three
additional discontinuations included rash (n=2) and a motor
vehicle accident with facial fractures (n=1).
Telaprevir and VX-222
Vertex has two oral medicines in development for the treatment
of genotype 1 chronic hepatitis C: telaprevir and VX-222. 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 chronic hepatitis
C have received telaprevir in Phase 2 and Phase 3 studies. Vertex
has been granted Priority Review for its applications for the
approval of telaprevir by the U.S. Food and Drug Administration
(FDA) and Health Canada. 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
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.
VX-222 is an investigational, oral, non-nucleoside inhibitor
of HCV NS5B polymerase. VX-222 is currently being evaluated
in combination with telaprevir, pegylated-interferon and ribavirin
in a Phase 2 study. Vertex has worldwide commercial rights for
Pharmaceuticals. Interim Phase 2 Data Showed Rapid Viral Response
to VX-222 in Combination with Telaprevir, Pegylated-Interferon
and Ribavirin Among People With Hepatitis C. Press release.
March 31, 2011.