Published: November 05, 2011
Interim Data from Phase 2 Study Showed 93% of People with Hepatitis C Who Received a Total of 12 Weeks of a Combination Regimen Including INCIVEK (telaprevir) and VX-222 (400mg) Achieved a Viral Cure (SVR)
SAN FRANCISCO - (BUSINESS WIRE) - Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today
interim results from ZENITH, an ongoing Phase 2 study designed to assess
the safety, tolerability and efficacy of multiple 12- and 24-week
response-guided treatment regimens with VX-222 (100mg or 400mg), its
lead polymerase inhibitor in development, in combination with INCIVEK
(telaprevir ) tablets, pegylated-interferon and ribavirin in people with
genotype 1 chronic hepatitis C who were new to treatment. On the basis
of the results announced today and previously announced data from other
treatment arms of the ZENITH study, Vertex intends to start a Phase 3
study to evaluate a total treatment duration of 12 weeks with this
four-drug regimen in treatment naïve and relapser patients with genotype
1 chronic hepatitis C.
Data from the four-drug treatment arms (C and D) of ZENITH were
announced today and showed that, regardless of treatment duration, 90
percent of patients in the VX-222 (400mg) group had undetectable levels
of hepatitis C virus in the blood 12 weeks after the end of treatment
(sustained viral response 12, or SVR12). Fifty percent (15/30) of
patients who received the combination regimen including VX-222 (400mg)
were eligible for a total of 12 weeks of treatment and 93 percent
(14/15) of them achieved a viral cure (sustained viral response, or
SVR). For patients in the VX-222 (400mg) arm who received an additional
12 weeks of pegylated-interferon and ribavirin alone, 87 percent (13/15)
had undetectable hepatitis C virus 12 weeks after treatment ended. Study
results also showed that patients treated with the four-drug regimen
experienced a rapid viral response; more than 85 percent had
undetectable heptatitis C virus in the blood at week four of treatment.
The most frequent adverse events (≥20 percent) observed in the four-drug
treatment arms were fatigue, nausea, diarrhea, anemia, pruritis
(itchiness), insomnia and rash. Interim data from ZENITH will be
presented during a late-breaker poster session at The Liver Meeting,
the 62nd Annual Meeting of the American Association for the
Study of Liver Diseases (AASLD), in San Francisco November 4-8, 2011.
"More than 85 percent of patients in the four-drug treatment arms of
ZENITH had undetectable hepatitis C virus at week 4 and, regardless of
treatment duration, 90 percent of them cleared the hepatitis C virus,"
said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief
Medical Officer at Vertex. "Based on these interim results, Vertex began
discussions with regulatory agencies about the regulatory path for this
four-drug regimen, with the intent to initiate Phase 3 studies in a
broad group of people with genotype 1 hepatitis C in the first quarter
of 2012."
"The potential to achieve high viral cure rates with just 12 weeks of
therapy is an exciting prospect for the future of treatment," said David
R. Nelson, M.D., Professor of Medicine at the University of Florida
College of Medicine, Director of the UF Clinical and Translational
Science Institute and Principal Investigator of the trial.
Patients in Arms C and D of ZENITH were assigned to receive all four
drugs for the first 12 weeks of treatment. People who had undetectable
hepatitis C virus levels in the blood (HCV RNA) at weeks two and eight
were eligible to stop all treatment at week 12. The remaining patients
were assigned to receive pegylated-interferon and ribavirin alone for an
additional 12 weeks for a total of 24 weeks of treatment. In this study,
VX-222, INCIVEK and ribavirin were given twice daily (BID).
Arms A (n=18) and B (n=29) of ZENITH were designed to evaluate all-oral,
two-drug combination regimens of VX-222 (100 mg or 400 mg) and INCIVEK
(1,125 mg). There was significant initial antiviral activity in people
who were treated with VX-222 (400 mg) and INCIVEK in Arms A and B.
However, as previously announced, these treatment arms were discontinued
due to a pre-defined stopping rule related to viral breakthrough.
Two additional treatment arms (E and F) were added to the study to
evaluate a 12-week, three-drug, all-oral, interferon-free regimen of
VX-222 (400 mg), INCIVEK and ribavirin. Arm E (n=23) is evaluating
people with genotype 1b chronic hepatitis C and Arm F (n=23) is
evaluating people with genotype 1a chronic hepatitis C. Vertex expects
to provide end-of-treatment data from the all-oral arms of the study in
early 2012.
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|
|
ZENITH: Efficacy Results for All Patients in Arms C & D Who
Completed Treatment
|
|
|
Undetectable hepatitis C
virus at week 24 for all
patients
(intent-to-treat
analysis)
|
SVR24 in people
who were assigned to 12
total
weeks of
treatment
|
Undetectable hepatitis C
virus in people who were
assigned
to 24 weeks of
treatment (SVR12)
|
|
Arm D: VX-222 (400 mg),
INCIVEK, pegylated-
interferon
and ribavirin*
(n=30)
|
90%
(27/30)
|
93%
(14/15)+
|
87%
(13/15)
|
|
Arm C: VX-222 (100 mg),
INCIVEK, pegylated-
interferon
and ribavirin**
(n=29)
|
83%
(24/29)
|
82%
(9/11) ++
|
83%
(15/18)
|
|
SVR12: undetectable hepatitis C virus 12 weeks after treatment
ended.
*50 percent (15/30) had undetectable
hepatitis C virus at weeks 2 and 8 and were eligible to stop all
treatment at week 12. Two people in the VX-222 (400 mg) treatment
arm discontinued treatment before week 12 and did not achieve
SVR12.
**38 percent (11/29) had undetectable
hepatitis C virus at weeks 2 and 8 and were eligible to stop all
treatment at week 12. Four people in the VX-222 (100 mg) treatment
arm discontinued treatment before week 12 and two of them achieved
SVR12.
+One person in the 12-week VX-222 (400 mg)
treatment arm relapsed.
++Two people in the 12-week VX-222 (100 mg)
treatment arm relapsed.
In ZENITH, the amount of hepatitis C virus in the blood was
measured by the Roche COBAS Taqman HCV
test with a limit of quantification of <25 IU/mL).
|
The most frequent adverse events (≥20 percent) observed in the four-drug
treatment arms (C and D) were fatigue, nausea, diarrhea, anemia,
pruritis (itchiness), insomnia and rash. The majority of events were
mild or moderate. Severe events observed in at least two patients were
neutropenia, hypomagnesemia and anemia. Three people in each study arm
discontinued treatment before week 12 and one person in each arm
discontinued treatment between weeks 12 and 24 while they were receiving
pegylated-interferon and ribavirin alone. No patient discontinued
treatment due to gastrointestinal symptoms or viral breakthrough.
About ZENITH
ZENITH is an ongoing Phase 2 study that initially enrolled 106 people
with genotype 1 chronic hepatitis C and began with four treatment arms
designed to evaluate multiple response-guided treatment regimens with
VX-222, Vertex's lead polymerase inhibitor in development, in
combination with INCIVEK, Pegasys (pegylated-interferon
alfa-2a) and Copegus (ribavirin), three medicines approved
to treat hepatitis C. The primary endpoint of the study is safety and
tolerability. The secondary endpoint is on-treatment antiviral activity
and the proportion of people in each treatment arm who achieve a
sustained viral response.
Updates on Vertex's Development Plans in Hepatitis C
Vertex has several studies planned and ongoing designed to evaluate a
total of 12 weeks of treatment for people with genotype 1 chronic
hepatitis C.
Four-drug "QUAD" Regimens
Based on the results from ZENITH announced today and previously
announced data from other treatment arms of the ZENITH study, Vertex is
in discussions with regulatory agencies about the regulatory path for
the four-drug regimen, with the intent to start a Phase 3 study
evaluating a total treatment duration of 12 weeks in people with
genotype 1 chronic hepatitis C who are new to treatment or who relapsed
after at least one prior course of treatment with pegylated-interferon
and ribavirin alone.
Vertex is also in discussions with regulatory agencies regarding two
additional studies designed to evaluate 24- and 48-week response-guided,
four-drug regimens in patients who are new to treatment and also have
cirrhosis (scarring of the liver) and, separately, those who have not
responded (partial and null responders) to at least one prior course of
treatment with pegylated-interferon and ribavirin alone.
Interferon-Free, 12-Week Regimens
Vertex expects to provide end-of-treatment data from the all-oral arms
(E and F) of ZENITH study in early 2012. These study arms are evaluating
a 12-week regimen of VX-222, INCIVEK and ribavirin. Dosing for all
patients is expected to be complete in December 2011.
12-Week INCIVEK Combination Regimen for IL28B Patients
In October 2011, Vertex announced the start of the Phase 3b CONCISE
study that is designed to evaluate 12 weeks of INCIVEK in combination
with pegylated-interferon and ribavirin among people with genotype 1
chronic hepatitis C who have the 'CC' variation near the IL28B gene.
About INCIVEK and VX-222
INCIVEK (telaprevir) tablets is an oral medicine that acts directly on
the hepatitis C virus protease, an enzyme essential for viral
replication. INCIVEK is the most prescribed direct-acting antiviral for
the treatment of genotype 1 chronic hepatitis C and has been used to
treat more than 17,000 people in the United States.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in
May 2011 and by Health Canada in August 2011 for people with genotype 1
chronic hepatitis C with compensated liver disease (some level of damage
to the liver but the liver still functions), including cirrhosis
(scarring of the liver). INCIVEK is approved for people who are new to
treatment, and for people who were treated previously but who did not
achieve a sustained viral response, or viral cure (relapsers, partial
responders and null responders).
VX-222 is an oral medicine in development that is a non-nucleoside
inhibitor of the HCV NS5B polymerase. VX-222 is currently being
evaluated in combination with INCIVEK, pegylated-interferon and
ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for
VX-222.
INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12
weeks in combination with pegylated-interferon and ribavirin. Each
monthly package of INCIVEK contains four weekly boxes that include daily
blister strips. After the first 12 weeks, all patients stop receiving
INCIVEK and continue treatment with pegylated-interferon and ribavirin
alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK
combination therapy, more than 60 percent of people treated for the
first time, as well as those who relapsed after previous therapy, are
expected to complete all treatment in 24 weeks. All other patients
receive a total of 48 weeks of treatment. A Phase 3 study evaluating
twice-daily dosing of INCIVEK is ongoing.
Rash and anemia are the most serious side effects associated with
INCIVEK, which led to treatment discontinuation in about 1 percent of
people in clinical studies. The most common side effects reported with
INCIVEK combination treatment include fatigue, itching, nausea,
diarrhea, vomiting, anal or rectal problems, and taste changes.
Vertex developed telaprevir in collaboration with Tibotec BVBA and
Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir
in North America where it is being marketed under the brand name INCIVEK
(in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to
commercialize telaprevir in Europe, South America, Australia, the Middle
East and certain other countries. In September 2011, telaprevir was
approved in the European Union and Switzerland. Telaprevir is known as
INCIVO in Europe. Mitsubishi Tanabe Pharma has rights to
commercialize telaprevir in Japan and certain Far East countries. In
September 2011, telaprevir was approved in Japan and will be known as
Telavic.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK (telaprevir) is a prescription medicine used with the medicines
peginterferon alfa and ribavirin to treat chronic (lasting a long time)
hepatitis C genotype 1 infection in adults with stable liver problems,
who have not been treated before or who have failed previous treatment.
It is not known if INCIVEK is safe and effective in children under 18
years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa
and ribavirin. Ribavirin may cause birth defects or death of an unborn
baby. Therefore, a patient should not take INCIVEK combination treatment
if she is pregnant or may become pregnant, or if he is a man with a
sexual partner who is pregnant. Patients must use two forms of effective
birth control during treatment and for the 6 months after treatment with
these medicines.
INCIVEK and other medicines can affect each other and can also cause
side effects that can be serious or life threatening. There are certain
medicines patients cannot take with INCIVEK combination treatment.
Patients should tell their healthcare providers about all the medicines
they take, including prescription and non-prescription medicines,
vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The
most common side effects of INCIVEK include itching, nausea, diarrhea,
vomiting, anal or rectal problems, taste changes and tiredness. There
are other possible side effects of INCIVEK, and side effects associated
with peginterferon alfa and ribavirin also apply to INCIVEK combination
treatment. Patients should tell their healthcare providers about any
side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the
Medication Guide, available at www.INCIVEK.com.
INCIVEK is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS and COPEGUS® are registered trademarks of
Hoffmann-La Roche.
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
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2
However, approximately 60 percent of people do not achieve SVR,3,4,5
or viral cure,6 after treatment with 48 weeks of
pegylated-interferon and ribavirin alone. If treatment is not successful
and a person does not achieve a viral cure, they remain at an increased
risk for progressive liver disease.7,8
More than 170 million people worldwide are chronically infected with
hepatitis C.6 In the United States, nearly 4 million people
have chronic hepatitis C and 75 percent of them are unaware of their
infection.9 Hepatitis C is four times more prevalent in the
United States compared to HIV.9 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.10
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.11,12 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
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 intent to initiate Phase 3 studies for the QUAD
regimen in the first quarter of 2012; (ii) the potential to achieve high
viral cure rates with just 12 weeks of therapy; (iii) Vertex's
discussions with regulatory authorities regarding future clinical trials
and (iv) end-of-treatment data from the all-oral arms of the ZENITH
study. 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 the interim data
presented in this press release may not be predictive of the final
outcomes from this clinical trial; the outcomes from additional arms in
this clinical trial and/or from any future clinical trials of
telaprevir/VX-222 may not be favorable; 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 www.vrtx.com.
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 discovers,
develops and commercializes 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, rheumatoid arthritis, 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.
Today, Vertex has more than 1,900 employees around the world, and Science
magazine named Vertex number one on its 2011 list of Top Employers in
the life sciences.
INCIVEKTM is a trademark of Vertex Pharmaceuticals
Incorporated.
PEGASYS and COPEGUS® are registered trademarks of
Hoffmann-La Roche.
1 Centers for Disease Control and Prevention. Hepatitis C
Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf.
Accessed March 21, 2011.
2 Pearlman BL and Traub N. Sustained Virologic Response to
Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So
Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
3 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.
4 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.
5 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.
6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis,
management and treatment of hepatitis C; An update. Hepatology.
2009;49 (4):1-40.
7 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).
8 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.
9 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: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx.
Updated January 11, 2010. Accessed March 21, 2011.
10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C
virus (HCV): Costs of a baby boomer epidemic of liver disease. Available
at: http://www.natap.org/2009/HCV/051809_01.htm.
Updated May 2009. Accessed March 21, 2011. This report was
commissioned by Vertex Pharmaceuticals, Inc.
11 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.
12 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.
(VRTX-GEN)
Vertex Pharmaceuticals Incorporated
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Kalmar, 617-444-6992
mediainfo@vrtx.com
or
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or
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or
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or
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