Thursday, March 31, 2011

EASL Telaprevir Improved SVR Rates in People Whose Prior Treatment For Hepatitis C Was Unsuccessful

Results From Phase 3 REALIZE Study Showed Telaprevir-Based Therapy Improved SVR Rates in People Whose Prior Treatment For Hepatitis C Was Unsuccessful

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 statistically
significant rates of sustained viral response (SVR) compared to those
treated with pegylated-interferon and ribavirin alone.
REALIZE also evaluated whether SVR 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, Tibotec BVBA.
“These data showed higher sustained viral response rates for patients
treated with a telaprevir-based regimen compared to re-treatment with
currently available medicines,” said Stefan Zeuzem, M.D., Professor of
Medicine and Chief of the Department of Medicine at the JW Goethe
University Hospital, Frankfurt, Germany and principal investigator for
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 SVR
compared to 24 percent (16/68), 15 percent (4/27) and 5 percent (2/37),
respectively, who received pegylated-interferon and ribavirin. The SVR
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 SVR.
“Rates of sustained viral response among those treated with
telaprevir-based regimens were similar between the simultaneous and
delayed start arms of the study,” said Robert Kauffman, M.D., Ph.D.,
Senior Vice President and Chief Medical Officer for Vertex.
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.

Summary of REALIZE Results
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 weeks.
SVR Results % (n)
Prior Relapsers

Prior Partial Responders

Prior Null Responders
Simultaneous Start Arm+






Lead-In Arm++






Control Arm+++






*The 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 alone.

++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

+++Control: 12 weeks of placebo, PEG & RBV, followed by
36 weeks of Peg & RBV alone.

Prior 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 log in10 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.

Safety and Tolerability Information for the Phase 3 Studies of

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, pruritus, 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.
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 treatment arms.

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 SVR
after at least one course of prior treatment with interferon-based

Status of Telaprevir Regulatory Applications
The safety and efficacy of telaprevir for the treatment of chronic
hepatitis C is still under investigation. Authorization to market
telaprevir has not yet been obtained.
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 SVR after treatment with currently available medicines. For
complete information on the telaprevir clinical trials or a fact sheet
on the trial designs visit:

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 SVR.
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.

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 with 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 If treatment is not successful and a person does not achieve SVR,
they remain at an increased risk for progressive liver disease.5,6
Approximately 250,000 people in Canada have chronic hepatitis C and more
than a third of them do not know they are infected.7 Three
provinces account for 80 percent of hepatitis C infections in Canada:
Ontario (42 percent), British Columbia (22 percent) and Quebec (16
percent).8 Each year up to 5,000 people are newly infected
with hepatitis C, and in 2007 alone, nearly 8,000 people were infected.7,8 In 2010, the annual cost of hepatitis C due to medical treatment
and lost productivity in Canada was estimated to reach $1 billion.9 By
2022, the number of hepatitis C-related deaths is expected to increase
by one-third.10
PEGASYS® and COPEGUS® are 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 date of the scheduled meeting of the FDA’s Antivirial
Advisory Committee and (ii) the FDA's target review 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 there may be varying interpretations of the data from
the telaprevir clinical trials; that future outcomes from clinical
trials of telaprevir may not be favorable; that future scientific,
clinical, competitive or other market factors may adversely affect the
potential for telaprevir-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 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. and Canada.
For more information and to view Vertex's press releases, please visit
1 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.
3 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon
alfa-2a plus ribavirin for chronic hepatitis C virus infection. N
Engl J Med.
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 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).
6 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.
7 Public Health Agency of Canada. Hepatitis C: Get the facts.
You could have it and not know it.
Updated September 21, 2010. Accessed January 18, 2011.
8 Public Health Agency of Canada. Modeling the incidence of
prevalence of hepatitis C infection and its sequelae in Canada, 2007.
Updated October 20, 2010. Accessed January 18, 2011.
9 Public Health Agency of Canada. A renewed public health
response to address hepatitis C: A summary report of the
priority-setting process and strategic framework to action.
Updated June 2009. Accessed January 2011.
10 Sherman M, Sharfran S, Burak K, et al. Management of
chronic hepatitis C consensus guidelines. Can J Gastroenterol.
2007;21 (Suppl C):25C-34C.

Vertex Pharmaceuticals Incorporated
Dawn Kalmar
Zachry Barber
617-444-6992 or
Partridge, 617-444-6108
Lora Pike, 617-444-6755
Osborne, 617-444-6057

Telaprivir beats HCV standard care

Friday 1st April 2011

Telaprevir-based regimens are significantly better than standard care for treatment-experienced hepatitis C patients, research suggests.

Tibotec Virco-Virology BVBA has announced that a significantly greater proportion of patients who have previously failed treatment for chronic genotype 1 hepatitis C virus (HCV) achieved a sustained viral response (SVR) with 12 week telaprevir combination regimens than with the current standard of care, pegylated-interferon and ribavirin, alone.

Telaprevir is an investigational DAA (Direct Acting Antiviral) being co-developed by Tibotec and Vertex Pharmaceuticals.

Final data from the REALIZE trial were presented today at the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin.

SVR, which means the virus remains undetectable in patients' blood six months after completion of treatment, is the goal of HCV treatment and is considered a cure.

An estimated 170 million people globally suffer from chronic HCV and approximately 10-20 percent of these people will develop cirrhosis and liver failure.

Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and HCV is the most common cause of liver transplant in Europe.

"These groundbreaking data show that a telaprevir combination regimen significantly improves cure rates for patients with genotype 1 HCV, the most common form of the virus, who have failed previous treatment," said lead investigator Professor Stefan Zeuzem, Chief of the Department of Medicine, Johann Wolfgang Goethe University Hospital, Frankfurt, Germany.

"Significant advancements in treatment such as this will make a real difference in reducing the burden of HCV."

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