Friday, April 1, 2011

EASL "VX-222 Plus Telaprevir,Peg/Riba" Interim Phase 2 Data; Undetectable Viral Load At 12wks

Vertex said Thursday  the combination of telaprevir and VX-222 with pegylated-interferon and ribavirin treatment in HCV genotype 1, naive - "never treated before" patients met its safety goal . The four drug combination showed that 90% of participants were undetectable by week 12.

Previously ,Vertex halted other arms of telaprevir and VX-222 ; In October of 2010 the VX-222/telaprevir combo being tested in low doses was stopped because of viral breakthrough. In December 2010 in a higher dose of the VX-222/telaprevir combo was halted in part of the Vertex study.

Also See HIV and Hepatitis
4-Drug Combo with Telaprevir and VX-222 Clears
HCV at 12 Weeks
SUMMARY: 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.

Interim Phase 2 Data Showed Rapid Viral Response to VX-222 in Combination with Telaprevir, Pegylated-Interferon and Ribavirin Among People With Hepatitis C

BERLIN--(BUSINESS WIRE)--Mar 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, M.D., Ph.D., 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, M.D., 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 C. 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 and ribavirin. 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.

ZENITH: Interim Intent to Treat (ITT) Analysis of Arms C and D

VX-222 (100 mg) /TVR-


VX-222 (400 mg) /TVR-based arm(++)
Week 2 HCV RNA


Week 2 and 8 HCV



Week 4 HCV RNA



12 HCV RNA undetectable



was evaluated using the TaqMan assay version 2.0.

*As 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(R) (pegylated-interferon alfa-2a) and
Copegus(R) (ribavirin).

++VX-222 (400 mg, BID), telaprevir (1,125 mg, BID),
Pegasys(R) (pegylated-interferon alfa-2a) and
Copegus(R) (ribavirin).
Preliminary 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
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).

About 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 (PDUFA).
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

About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C
virus, which is spread through direct contact with the blood of
infected people and ultimately affects the liver.1
Chronic hepatitis C can lead to serious and life-threatening liver
problems, including liver damage, cirrhosis, liver failure or liver
cancer.1 Though many people with hepatitis C may not
experience symptoms, others may have symptoms such as fatigue,
fever, jaundice and abdominal pain.1 Approximately 60
percent of people who undergo treatment of an initial 48-week
regimen of pegylated-interferon and ribavirin, the currently
approved medicines for genotype 1 hepatitis C, do not achieve
SVR,2,3,4 or viral cure.5 If treatment is not
successful and a person does not achieve a viral cure, they remain
at an increased risk for progressive liver
More than 170 million people worldwide are chronically infected
with hepatitis C.5 In the United States, nearly 4
million people have chronic hepatitis C and 75 percent of them are
unaware of their infection.8 The majority of people with
hepatitis C in the United States were born between 1946 and 1964,
accounting for two of every three people with chronic hepatitis
C.9 Hepatitis C is the leading cause of liver
transplantations in the United States and is reported to contribute
to 4,600 to 12,000 deaths annually.10,11 By 2029, total
annual medical costs in the United States for people with hepatitis
C are expected to more than double, from $30 billion in 2009 to
approximately $85 billion.9
registered trademarks of Hoffmann-La Roche.

Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as
defined in the Private Securities Litigation Reform Act of 1995,
including statements regarding (i) the potential importance of
reducing treatment time to 12 weeks and early data from this study
providing new information about the potential to do this with a
four-drug VX-222 regimen; (ii) the early data being encouraging
because the data showed patients had a very rapid decline in
hepatitis C virus as early as the second week of treatment; (iii)
the possibility that a sixth treatment arm may be added to the
trial; (iv) the date of the scheduled meeting of the FDA's
Antiviral Advisory Committee and (v) the FDA's target response date
for the telaprevir NDA. While the company believes the
forward-looking statements contained in this press release are
accurate, there are a number of factors that could cause actual
events or results to differ materially from those indicated by such
forward-looking statements. Those risks and uncertainties include,
among other things, that Vertex could experience unforeseen delays
in obtaining approval to market telaprevir; that the interim
on-treatment data presented in this press release may not be
predictive of the final outcomes from this clinical trial, outcomes
from any future clinical trials of telaprevir/VX-222 may not be
favorable; that future scientific, clinical, competitive or other
market factors may adversely affect the potential for
telaprevir/VX-222-based therapy and the other risks listed under
Risk Factors in Vertex's annual report and quarterly reports filed
with the Securities and Exchange Commission and available through
Vertex's website at

Vertex disclaims any obligation to update the
information contained in this press release as new information
becomes available.

About Vertex
Vertex 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
Founded more than 20 years ago in Cambridge, MA, we now have
ongoing worldwide research programs and sites in the U.S., U.K. and
For more information and to view Vertex's press releases, please

Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: . Accessed March 21, 2011.

2 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

3 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

4 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

6 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

7 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

8 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: Updated January 11, 2010. Accessed March 21, 2011.

9 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.

10 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

11 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.

Contact: Vertex Pharmaceuticals Incorporated


Dawn Kalmar, 617-444-6992

Amy Pasqua, 617-444-6992

Zachry Barber, 617-444-6992



Michael Partridge, 617-444-6108

Lora Pike, 617-444-6755

Matthew Osborne, 617-444-6057

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