HCV
Advocate easl 2007 News Review
EASL 2007 Index
Update -
Hepatitis C
·
Human Genome Sciences Reports Positive
Interim Results of Phase 2b Trial of Albuferon(R)
Hepatitis B
Download PDF version of
this News Review:
Interim Results Presented at EASL from PROVE 1
Clinical Trial of Investigational Drug Telaprevir in Patients with Genotype 1
Hepatitis C
PROVE 1 data support potential to shorten treatment
duration in treatment-naïve, genotype 1 HCV patients
Barcelona, Spain, April
14, 2007 – In a late-breaker presentation at the 42nd Annual Meeting of the European
Association for the Study of the Liver (EASL), researchers today presented data
from a planned interim analysis of the PROVE 1 clinical trial, which is the
first trial to evaluate short-duration therapy with the investigational
hepatitis C protease inhibitor telaprevir (TVR, VX-950) in combination with
pegylated interferon (peg-IFN) and ribavirin (RBV) in treatment-naïve, genotype
1-infected hepatitis C patients. The data from PROVE 1 demonstrated a high rate
of rapid viral response (RVR) in the telaprevir groups and a low rate of
on-treatment viral breakthrough, and suggested that 12 weeks of
telaprevir-based therapy enabled some patients to clear the virus. Vertex
Pharmaceuticals Incorporated (Nasdaq: VRTX) is developing telaprevir in
collaboration with Tibotec.
“The high rates of RVR observed in
the telaprevir groups in PROVE 1, and the fact that some patients have remained
persistently viral negative 20 weeks after stopping the 12 weeks of
telaprevir-based therapy, suggest that we may be able to shorten the treatment
duration in genotype 1 HCV patients,” said John McHutchison, M.D., Principal
Investigator for the PROVE 1 study and Director of Gastroenterology and
Hepatology Research at Duke Clinical Research Institute. “These interim results
are encouraging and suggest that high sustained viral response (SVR) rates may
be achieved with regimens that are 24 weeks in total duration. We look forward
to 24 week follow-up data from the initial group of patients who stopped
treatment at 12 weeks, and follow-up data from patients in the study who
received 24 weeks of treatment.”
PROVE 1 Summary
- 88% and 79% of
patients receiving telaprevir achieved a rapid viral response (RVR) as
measured by plasma HCV RNA <30 IU/mL and <10 IU/mL, respectively, at
4 weeks.
- Six of 9 patients
in one treatment arm who completed 12 weeks of treatment, and who had
achieved an RVR as defined by the study protocol (<10 IU/mL), continued
to have undetectable HCV RNA 20 weeks after stopping all treatment
(“SVR20”).
- The treatment discontinuation
rate due to adverse events through 12 weeks was 11% in telaprevir arms and
3% in the control arm. Rash, gastrointestinal events and anemia were the
most common events leading to discontinuation in the telaprevir arms.
“These interim results support our
approach to evaluating telaprevir-based regimens of differing durations in our
Phase 2 program. The results of the 12-week duration regimen provide a level of
confidence in the shorter duration approach, and we look forward to safety and
antiviral data, including SVR data, from the 24-week telaprevir-based
regimens,” said John Alam, M.D., Executive Vice President, Medicines
Development, and Chief Medical Officer of Vertex. “The information from PROVE 1
and PROVE 2 should allow us to design optimized durations and regimens for
Phase 3 development.”
PROVE 1 and PROVE 2 represent two
of three large, ongoing clinical studies of telaprevir. In aggregrate, the
three studies are designed in part to evaluate the safety and antiviral
activity of different durations of telaprevir-based therapy in genotype-1
infected HCV treatment-naïve and treatment-failure patients, both with and
without ribavirin. Taken together, the PROVE studies are expected to provide
information to optimize the treatment duration and treatment regimen for
telaprevir-based therapy.
PROVE 1: Implications
for Clinical Development and Registration Path
Vertex today discussed the potential implications that the new information from
PROVE 1 has for future clinical development of telaprevir. Vertex stated its
intention to consider evaluation of treatment regimens that would include
telaprevir in combination with peg-IFN and RBV, and depending on PROVE 2 data,
regimens that may exclude RBV. Vertex expects to focus on treatment durations
of no more than 24 weeks. Vertex and Tibotec are planning to meet with
regulatory authorities to discuss the Phase 3 design in mid-2007 and are
planning to initiate Phase 3 clinical development in the fourth quarter of
2007. The registration strategy and timing of an NDA filing will be dependent
on discussions with regulatory authorities.
PROVE 1 Results at EASL
Interim 12-week antiviral analysis of
PROVE 1
A total of 250 patients were enrolled in PROVE 1 and received at least one dose
of telaprevir or placebo in addition to Peg-interferon alfa-2a (peg-IFN) +
ribavirin (RBV) in the study. A total of 175 patients received at least one
dose of telaprevir in 1 of 3 arms (treatment arms B, C and D) and 75 patients
received at least one dose of placebo (arm A). Treatment with telaprevir
resulted in a high proportion of patients achieving a rapid viral response at 4
weeks. At the time of the interim analysis, all patients had either completed
12 weeks or discontinued from the study prior to week 12. Available 4-week and
12-week results are detailed in the following table:
In PROVE 1, a low rate of viral
breakthrough was observed. Viral breakthrough occurred in 12 patients receiving
telaprevir (7%), all but one of which occurred in the first 4 weeks of
treatment.
Analysis of PROVE 1 Patients who
Finished All Treatment at 12 Weeks
Seventeen of 175 patients received at least one dose of telaprevir in “Arm D”
of the PROVE 1 study (telaprevir + peg-IFN + RBV). According to the study
protocol, patients in Arm D were eligible to stop all treatment at week 12 if
they met on-treatment criteria, including the achievement of RVR (<10 IU/mL
at week 4) and maintenance of this viral response (<10 IU/mL) at week 10 of
treatment. Nine of 17 patients met these criteria and stopped therapy at 12
weeks, and 6 of these patients continued to have undetectable HCV RNA at week
20 of post-treatment follow-up. Of the remaining 8 patients enrolled in Arm D,
4 discontinued due to adverse events prior to week 12, and 4 did not achieve
RVR.
Interim 12-Week Safety Analysis of
PROVE 1
In PROVE 1, the types of adverse events that have been commonly observed with
interferon and ribavirin were seen across all treatment arms. The most common
adverse events, regardless of treatment assignment, were fatigue, rash,
headache and nausea. Gastrointestinal disorders, rash and anemia were more
common in the telaprevir arms.
In the telaprevir dosing arms, the
incidence of treatment discontinuations due to adverse events through 12 weeks
was 11% (19 of 175 patients), compared to 3% (2 of 75 patients) in the control
arm. The difference between the two groups is due to the greater number of
discontinuations due to rash, gastrointestinal disorders and anemia in the
telaprevir arms compared to the control arm. The most common reason for
treatment discontinuation in the telaprevir arms was rash (7 patients), and the
median time to discontinuation in these patients was 64 days.
Webcast of Investor
Presentation
Vertex intends to provide a live webcast of its investor presentation from
Barcelona beginning at 7:30 p.m. CEST (1:30 p.m. EDT) on Saturday, April 14.
The presentation may be accessed from the ‘Events Calendar’ on the homepage of
Vertex’s website at www.vrtx.com. A replay of the webcast will also be
available on the Company’s website until April 27, 2007. To ensure a timely
connection, it is recommended that users register at least 15 minutes prior to
the scheduled webcast.
About Telaprevir
(VX-950)
Telaprevir (VX-950) is an investigational oral inhibitor of HCV protease, an
enzyme essential for viral replication, and is one of the most advanced
investigational agents in development that specifically targets HCV. Vertex is
conducting a global Phase 2b clinical development program for telaprevir
consisting of three large clinical trials that are expected to enroll
approximately 1,000 patients with genotype-1 HCV at clinical centers in the
United States, Canada and Europe. In these clinical trials, telaprevir is being
dosed as 750 mg every eight hours in combination with pegylated interferon
alfa-2a (Pegasys®), both with and without ribavirin (Copegus®).
Vertex retains commercial rights
to telaprevir in North America. Vertex and Tibotec are collaborating to develop
and commercialize telaprevir in Europe, South America, Australia, the Middle
East, and other countries. Vertex is collaborating with Mitsubishi Pharma to
develop and commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by infection with hepatitis C virus
(HCV), which is found in the blood of people with the disease. HCV, a serious
public health concern affecting 170 million people worldwide, is spread through
direct contact with the blood of an infected person. Though many people with
hepatitis C may not experience symptoms, others may have symptoms such as
jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly
increases a person’s risk of developing chronic liver disease, cirrhosis, liver
cancer and early death.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed
to the discovery and development of breakthrough small molecule drugs for
serious diseases. The Company’s strategy is to commercialize its products both
independently and in collaboration with major pharmaceutical companies.
Vertex’s product pipeline is focused on viral diseases, inflammation,
autoimmune diseases, cancer, pain and bacterial infection. Vertex co-discovered
the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
About Tibotec
Tibotec Pharmaceuticals, Ltd., based in Cork, Ireland, is a pharmaceutical
research and development company. Tibotec is dedicated to the discovery and
development of innovative HIV/AIDS drugs and anti-infectives for diseases of
high unmet medical need. The Company’s main research and development facilities
are in Mechelen, Belgium with offices in Yardley, PA.
For further information on Tibotec, please visit www.tibotec.com
Safe Harbor Statement
This press release my contain forward-looking statements, including statements
that (i) PROVE 1 data support potential to shorten treatment duration and
increase SVR rates in patients with genotype 1 HCV infection; (ii) 12 weeks of
telaprevir-based therapy enabled some patients to clear the virus; (iii) high
SVR rates with telaprevir may be achieved with regimens that are no longer than
24 weeks in duration; (iv) interim results support our approach to evaluating
telaprevir-based regimens of differing durations in our Phase 2 program; (v)
the information from PROVE 1 and PROVE 2 will allow us to design optimized
durations and regimens for Phase 3 development; (vi) the PROVE studies are
expected to provide information to optimize treatment duration and treatment
regimen for telaprevir-based therapy; (vii) Vertex will consider evaluation of
treatment regimens that would include telaprevir in combination with peg-IFN
and RBV, and depending on PROVE 2 data, regimens that may exclude RBV; (viii)
Vertex expects to focus on treatment durations of no more than 24 weeks; and
(ix) Vertex and Tibotec are planning to meet with regulatory authorities to
discuss the Phase 3 design in mid-2007 and are planning to initiate Phase 3
clinical development in the fourth quarter of 2007. While management makes its
best efforts to be accurate in making forward-looking statements, such
statements are subject to risks and uncertainties that could cause the actual
results of studies to vary materially. Those risks and uncertainties include,
among other things, the risk that observed outcomes in clinical investigations
of small numbers of patients will not be reflected in clinical trials involving
larger numbers of patients, that unexpected and adverse outcomes in other
ongoing clinical and nonclinical studies will occur, that the FDA or other
regulatory authorities will require additional and unanticipated studies or
clinical trial outcomes before granting regulatory approval, and other risks
listed under Risk Factors in Vertex’s Form 10-K filed with the Securities and
Exchange Commission on March 1, 2007. Vertex disclaims any obligation to update
the information contained in this press release as new data become available.
Vertex Contacts:
Lynne H. Brum, VP, Strategic Communications (617) 444-6614
Michael Partridge, Director, Corporate Communications, (617) 444-6108
Patricia Farrell, Director, Public Relations, (617) 444-6533
Lora Pike, Manager, Investor Relations, (617) 444-6755
Zachry Barber, Senior Media Relations Specialist, (617) 444-6470
Tibotec Contact:
Karen Manson, VP Communications and Public Affairs
Mobile: +32 479 894 799
Office: +32 15 461 019
Human Genome Sciences Reports Positive Interim Results of Phase 2b Trial of Albuferon(R)
ROCKVILLE, Md., April 14
/PRNewswire-FirstCall/ -- Human Genome Sciences, Inc. today reported results at
Week 12 following the completion of therapy (SVR12) in a Phase 2b clinical trial of Albuferon(R)
(albinterferon alfa-2b) in combination with ribavirin in patients with genotype
1 chronic hepatitis C who are naive to interferon alpha-based treatment
regimens. The results were presented over the weekend in Barcelona at the 42nd
Annual Meeting of the European Association for the Study of the Liver (EASL).
"The interim data presented
at EASL suggest that Albuferon may offer efficacy at least comparable to
peginterferon alfa-2a, with half the injections and the potential for less
impairment of quality of life," said Stefan Zeuzem, M.D., Professor of
Medicine and Chief, Department of Medicine, J.W. Goethe University
Hospital (Frankfurt, Germany), and a clinical investigator in
the Phase 2b trial. "We look forward to continuing the evaluation of
Albuferon in larger populations in Phase 3 trials."
The interim results of
the Phase 2b trial demonstrated that Albuferon provided at least comparable
efficacy vs. Pegasys. The treatment group receiving Albuferon 900-mcg doses
every two weeks achieved a 59% rate of sustained virologic response at 12 weeks
following completion of therapy (SVR12), vs. 54% for Pegasys administered once
every week (ITT analysis). This Albuferon treatment group also had more
favorable health-related
quality- of-life scores than the Pegasys treatment group. All Albuferon doses
provided efficacy at least comparable to Pegasys. Among treatment-adherent
patients, 73% of those in the combined groups receiving Albuferon every two
weeks achieved SVR12, versus 63% for patients receiving Pegasys once a week.
Interim Results by Treatment Group
The interim results of
the Phase 2b trial at Week 12 following the completion of therapy include the
following virologic response rates (SVR12) and other findings:
Albuferon 900-mcg Every Two Weeks(Albuferon 900 Q2) -- Based on an
intention-to-treat (ITT) analysis, 59% of patients in the Albuferon 900 Q2
treatment group achieved SVR12, vs. 54% for Pegasys administered every week. --
Among treatment-adherent patients, 74% of those in the Albuferon 900 Q2
treatment group achieved SVR12, versus 63% for Pegasys. -- In heavier patients
(greater than or equal to 75 kg) who were treatment-adherent, 81% of those in
the Albuferon 900 Q2 treatment group achieved SVR12, versus 57% for Pegasys. --
Based on the SF-36 Heath Survey,
patients in the Albuferon 900 Q2 treatment group reported less impairment of
health-related quality of life, compared with patients in the Pegasys treatment
group, as measured by both physical component and mental component SF-36
summary measures at all time-points throughout the 48-week treatment period. --
At Weeks 12 and 24, fewer working patients in the Albuferon 900 Q2 treatment
group reported missing 7 days or more of work during the previous month, vs.
the Pegasys group (Week 12: 4% for Albuferon 900 Q2 vs. 17% for Pegasys; Week
24: 5% for Albuferon 900 Q2, vs. 22% for Pegasys). -- The rate of
discontinuations due to adverse events was 9% in the Albuferon 900 Q2 treatment
group, vs. 6% in the Pegasys group.
"The 900-mcg
Albuferon dose has the potential to offer patients an attractive therapeutic
option, given the favorable antiviral response data, more favorable quality of
life effects, and half as many injections," said David C. Stump, M.D.,
Executive Vice President, Research and Development, HGS.
Albuferon 1200-mcg Every Two Weeks (Albuferon 1200 Q2) -- ITT
analysis shows that 56% of patients in the Albuferon 1200 Q2 treatment group
achieved SVR12, vs. 54% for Pegasys administered every week. -- Among
treatment-adherent patients, 72% of those in the Albuferon 1200 Q2 treatment
group achieved SVR12, versus 63% for Pegasys. -- In heavier patients (greater
than or equal to 75 kg) who were treatment-adherent, 70% of those in the
Albuferon 1200 Q2 treatment group achieved SVR12, versus 57% for Pegasys every
week. -- ITT analysis shows that the Albuferon 1200 Q2 treatment group
exhibited a robust early antiviral response (reduction in hepatitis C
RNA viral load to below the level of quantitation): 75% for Albuferon 1200 Q2
at Week 12, vs. 66% for Pegasys. The Albuferon 1200 Q2 treatment group also had
the most rapid time to HCV
RNA negativity. -- The rate of discontinuations due to adverse events was 19%
in the Albuferon 1200 Q2 treatment group, vs. 6% in the Pegasys group. Adverse
events observed were those typically expected with interferon therapy. Dose reductions
were attempted in only 29% of subjects prior to discontinuation, versus 43% for
Pegasys.
"In the Albuferon
Phase 3 trials, we will strongly encourage titration of dose where necessary to
ensure tolerability and maximize the therapeutic benefit of the robust early
antiviral response offered by the 1200-microgram dose
on a two-week administration schedule," said Dr. Stump.
Albuferon 1200-mcg Every Four Weeks (Albuferon 1200 Q4) -- ITT
analysis shows that 53% of patients in the Albuferon 1200 Q4 treatment group
achieved SVR12, vs. 54% for Pegasys administered every week. -- Among
treatment-adherent patients, 68% of those in the Albuferon 1200 Q4 treatment
group achieved SVR12, versus 63% for Pegasys. -- In heavier patients (greater
than or equal to 75 kg) who were treatment-adherent, 67% of those in the
Albuferon 1200 Q4 treatment group achieved SVR12, versus 57% for Pegasys
administered once every week. -- The rate of discontinuations due to adverse
events was 12% in the Albuferon 1200 Q4 treatment group, vs. 6% in the Pegasys
group. Dose reductions due to hematologic adverse events were lowest in the
group receiving 1200-mcg Albuferon every four weeks (6% vs. 23% for Pegasys).
"We are encouraged
that Albuferon 1200-mcg dosed monthly achieved comparable efficacy vs. Pegasys
despite lower early virologic response," said
Dr. Stump. "We and
our collaborator, Novartis,
are currently planning an additional study to identify the optimal dose for
Albuferon dosed monthly."
The interim Phase 2b
results presented at EASL on Saturday, April 14 (Zeuzem S, Benhamou Y, Bain V,
McHutchison J, et al), include data available through Week 12 following
completion of 48 weeks of therapy for 458 patients who were enrolled in the
randomized, open-label, multi-center, active- controlled, dose-ranging trial.
The study was conducted in Australia, Canada, Czech Republic, France, Germany,
Israel, Poland and Romania. Patients were randomized into four treatment
groups, three of which received subcutaneously administered Albuferon (900 mcg
every two weeks, 1200 mcg every two weeks, and 1200 mcg every four weeks). The
fourth treatment group serves as the active control group and received 180-mcg
doses of subcutaneously administered peginterferon alfa-2a (Pegasys) once a
week. All patients received weight- based oral ribavirin daily. The primary
efficacy endpoint is sustained virologic response (SVR), defined as
undetectable viral load (HCV RNA < 10 IU/mL) at 24 weeks following
completion of therapy. Interim results at Week 12 following completion of
therapy are regarded as highly predictive of SVR.
Interim
Results of Phase 2 Trial in Genotype 2 or 3 Chronic Hepatitis C
An additional presentation at EASL
reported the interim results at Week 12 following the completion of therapy
(SVR12) in a randomized Phase 2 trial of Albuferon in combination with
ribavirin in 43 treatment-naive patients with genotype 2 or 3 chronic hepatitis
C (CHC). The interim results demonstrated that Albuferon dosed at 1500 mcg
every four weeks was well tolerated and exhibited robust antiviral activity in
these patients. Dose reductions due to hematologic adverse events stabilized by
Week 8 and recovered upon completion of therapy. These results support
additional evaluation of Albuferon in combination with ribavirin in a Phase 3
trial in patients with genotypes 2 and 3 CHC. The results also support further
evaluation of Albuferon at higher doses with monthly administration.
About
Albuferon
Albuferon is a novel long-acting
form of interferon alpha created by HGS using its proprietary albumin fusion technology.
Albuferon results from the genetic fusion of human albumin and interferon
alpha. Human albumin is the most prevalent naturally occurring blood protein in
the human circulatory system, persisting in circulation in the body for over
twenty days. Research has shown that genetic fusion of therapeutic proteins to
human albumin decreases clearance and prolongs the half-life of the proteins.
Recombinant interferon alpha is approved for the treatment of hepatitis C,
hepatitis B and a broad range of cancers.
Albuferon is being developed by
HGS and Novartis under an exclusive worldwide development and commercialization
agreement entered into in June 2006. Under the agreement, HGS and Novartis will
co-commercialize Albuferon in the United States, and will share clinical
development costs, U.S. commercialization costs and U.S. profits equally.
Novartis will be responsible for commercialization in the rest of the world and
will pay HGS a royalty on those sales. Clinical development, commercial
milestone and other payments to HGS could total as much as $507.5 million,
including $92.5 million received to date.
About
Hepatitis C
Hepatitis C is an inflammation of
the liver caused by the hepatitis C virus. It is estimated that as many as 170
million people worldwide are infected with hepatitis C virus. This includes
nearly four million people in the United States. When detectable levels of the
hepatitis C virus in the blood persist for at least six months, a person is
diagnosed as having chronic hepatitis C. The hepatitis C virus can cause
serious liver disease in a significant proportion of infected individuals,
leading to cirrhosis, primary liver cancer, and even death.
About
Human Genome Sciences
The mission of HGS is to apply
great science and great medicine to bring innovative drugs to patients with
unmet medical needs.
The HGS clinical development
pipeline includes novel drugs to treat hepatitis C, lupus, anthrax disease,
cancer, rheumatoid arthritis and HIV/AIDS. The Company's primary focus is rapid
progress toward the commercialization of its two lead compounds, Albuferon(R)
for hepatitis C, and LymphoStat-B(R) for lupus. Phase 3 clinical trials of both
compounds are now underway.
In June 2006, HGS announced that the
U.S. Government exercised its option under an existing contract to purchase
20,000 doses of ABthrax(TM) for the treatment of anthrax disease. Other HGS
drugs in clinical development include two TRAIL receptor antibodies for the
treatment of hematopoietic and solid malignancies, in addition to an antibody
to the CCR5 receptor for the treatment of HIV/AIDS.
For more information about HGS,
please visit the Company's web site at http://www.hgsi.com/
. For more information about Albuferon or to download copies of the EASL
presentations, please visit http://www.hgsi.com/products/albuferon.html
. To view the presentation of interim results of the Phase 2b trial of Albuferon
in treatment-naive genotype 1 hepatitis C patients, click here. To view the
presentation of interim results of the Phase 2 trial of Albuferon in
treatment-naïve genotype 2 or 3 hepatitis C patients, click here. Health
professionals or patients interested in Albuferon clinical trials or other
studies involving HGS products may inquire via the Contact Us section of the
Company's web site, http://www.hgsi.com/products/request.html
, or by calling us at (301) 610-5790, extension 3550.
HGS, Human Genome Sciences,
ABthrax, Albuferon and LymphoStat-B are trademarks of Human Genome Sciences,
Inc.
Safe
Harbor Statement
This
announcement contains forward-looking statements within the meaning of Section
27A of the Securities Act of 1933, as amended, and Section 21E of the
Securities Exchange Act of 1934, as amended. The forward-looking statements are
based on Human Genome Sciences' current intent, belief and expectations. These
statements are not guarantees of future performance and are subject to certain
risks and uncertainties that are difficult to predict. Actual results may
differ materially from these forward-looking statements because of the
Company's unproven business model, its dependence on new technologies, the
uncertainty and timing of clinical trials, the Company's ability to develop and
commercialize products, its dependence on collaborators for services and
revenue, its substantial indebtedness and lease obligations, its changing
requirements and costs associated with planned facilities and clinical trials,
intense competition, the uncertainty of patent and intellectual property
protection, the Company's dependence on key management and key suppliers, the
uncertainty of regulation of products, the impact of future alliances or
transactions and other risks described in the Company's filings with the
Securities and Exchange Commission. In addition, the Company will continue to
face risks related to animal and human testing, to the manufacture of ABthrax
and to FDA concurrence that ABthrax meets the requirements of the ABthrax
contract. If the Company is unable to meet the product requirements associated
with the ABthrax contract, the U.S. Government will not be required to
reimburse the Company for the costs incurred or to purchase any ABthrax doses.
Existing and prospective investors are cautioned not to place undue reliance on
these forward-looking statements, which speak only as of today's date. Human
Genome Sciences undertakes no obligation to update or revise the information
contained in this announcement whether as a result of new information, future
events or circumstances or otherwise.
http://www.newscom.com/cgi-bin/prnh/20010612/HGSLOGO
AP Archive:
http://photoarchive.ap.org/
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Desk,
Source:
Human Genome Sciences, Inc.
BARACLUDE(R) (entecavir) Therapy Resulted In
Undetectable Levels Of Hepatitis B Virus In Cohort Of Patients Who Re-Started
Treatment
Bristol-Myers Squibb Company (NYSE:
BMY) today announced data from a cohort of nucleoside-naive HBeAg-negative
chronic hepatitis B patients (ETV-027/901, n=99). These data showed that
patients who experienced recurrent levels of hepatitis B virus in the blood
after interruption of treatment with BARACLUDE(R) (entecavir) achieved viral
suppression and liver enzyme (ALT) normalization when re- treated for 48 weeks
with BARACLUDE. The study results were presented at the 42nd Annual Meeting of
the European Association for the Study of Liver Diseases (EASL) in Barcelona,
Spain.
In this cohort, 93 percent of patients who were re-treated with BARACLUDE had
undetectable viral load - the level of the hepatitis B virus in the blood -
(HBV DNA <300 copies/mL, measured by a common assay - polymerase chain
reaction or PCR) and 83 percent achieved liver enzyme normalization (ALT less
than or equal to 1xULN) after 48 weeks of therapy.
"This study showed that when treated again with BARACLUDE for 48 weeks,
patients achieved responses similar to those seen prior to treatment
interruption, with safety results consistent with previously reported
experience," said Hakan Senturk, MD, of the Ist.Univ.Cerrahpasa Tip Fak,
Istanbul, Turkey.
No deaths or treatment discontinuations due to adverse events were reported in
this cohort. The most common adverse events occurring in greater than 10
percent of patients were abdominal pain, fatigue, upper respiratory tract
infection, nasopharyngitis, increased ALT, arthralgia, and headache.
About the Nucleoside-Naive HBeAg-Negative BARACLUDE(R) (entecavir) Re-
Treatment Cohort
This analysis evaluated BARACLUDE(R) (entecavir) in nucleoside-naive chronic
HBeAg-negative patients who discontinued study therapy in ETV-027, and
subsequently restarted treatment in rollover study ETV-901, with a greater than
60 day gap between end of treatment in study ETV-027 and start of treatment in
study ETV-901.
-- ETV-027 compared 0.5 mg of BARACLUDE vs. 100 mg of lamivudine in
nucleoside-naive chronic HBeAg-negative chronic hepatitis B patients.
-- Rollover study ETV-901 was established as an open-label, follow-up protocol
for patients in phase II and III studies of BARACLUDE.
-- Due to ongoing blinding of study ETV-027, most patients retreated in ETV-901
initially received a combination of 1 mg of BARACLUDE plus 100 mg of
lamivudine, and were subsequently switched to 1 mg of BARACLUDE monotherapy.
The analysis cohort was defined regardless of treatment response at the end of
dosing in study ETV-027, and independent of virologic or ALT measurements at
the start of dosing in study ETV-901. During off-treatment follow-up, the
majority of patients had recurrent levels of hepatitis B virus in the blood
(viremia) and increases in ALT.
Data Results
At the end of dosing for study ETV-027:
-- 94 percent (n=93/99) of the re-treatment cohort had undetectable viral load
-- 78 percent (n=77/99) had ALT normalization
At entry into ETV-901:
-- Four percent (n=4/99) of patients had undetectable viral load
-- Eight percent (n=8/97) of patients had ALT normalization
Following re-treatment in study ETV-901:
-- 93 percent (n=82/88) of patients had undetectable viral load (HBV DNA
<300 copies/mL) by week 48 of re-treatment with BARACLUDE
-- 83 percent (n=79/95) of patients had ALT normalization (ALT less than or
equal to 1 times the upper limit of normal) by week 48 of re- treatment
BARACLUDE
Adverse events in study ETV-027/901 re-treatment cohort:
-- 67 percent (n=66/99) of patients experienced an adverse event. The most
common adverse events occurring in greater than ten percent of patients were
abdominal pain, fatigue, upper respiratory tract infection, nasopharyngitis,
increased ALT, arthralgia, and headache.
-- There were no deaths or treatment discontinuations due to adverse events.
-- Nine percent (n=9/99) of patients experienced a serious adverse event.
Serious adverse events included ALT elevation or hepatitis exacerbation (4),
bilirubin elevation (1), inguinal hernia (1), sialoadenitis (1),
thrombocytopenic purpura (1), groin pain (1), macular edema (1), urinary
incontinence (1) and cholelithiasis (1). Two of these events, hepatitis
exacerbation (1) and thrombocytopenia (1), were considered possibly related to
treatment by the investigator.
-- Five percent (n=5/99) of patients experienced an ALT flare on treatment (ALT
> 2 times baseline and >10 times the upper level of normal)
About BARACLUDE(R) (entecavir)
Discovered at Bristol-Myers Squibb, BARACLUDE(R) (entecavir) is a nucleoside
analogue indicated for the treatment of chronic hepatitis B virus infection in
adults with evidence of active viral replication with either evidence of
persistent elevations in serum aminotransferases (ALT or AST) or histologically
active disease. BARACLUDE has been approved in more than 60 countries and
regions around the world.
Important Information About BARACLUDE(R) (entecavir) 0.5mg/1mg Tablets
BARACLUDE(R) (entecavir) is a prescription medicine used for chronic infection
with hepatitis B virus (HBV) in adults where the virus is multiplying and
damaging the liver. BARACLUDE does not cure HBV or stop the spread of HBV to
others.
People should not take BARACLUDE if they are allergic to it or any of its
ingredients. BARACLUDE has not been studied in children and is not recommended
for anyone less than 16 years of age.
People taking BARACLUDE(R) (entecavir) should tell their healthcare provider
right away if they feel very weak or tired, have unusual muscle pain, have
trouble breathing, have stomach pain with nausea and vomiting, feel cold -
especially in their arms and legs, feel dizzy or lightheaded, or have a fast or
irregular heartbeat, as they may be signs of a serious condition called lactic
acidosis (buildup of an acid in the blood).
Lactic acidosis is a medical emergency and must be treated in the hospital.
Some people who have taken medicines like BARACLUDE have developed serious
liver problems called hepatotoxicity. This may occur with liver enlargement
(hepatomegaly) and fat in the liver (steatosis).
People should call their healthcare provider right away if they get any of the
following signs of liver problems: yellowing (jaundice) of the skin or the
white part of the eyes, darkening of the urine, lightening in the color of
bowel movements (stools), not feeling like eating food for several days or
longer, feeling sick to the stomach (nausea), or having lower stomach pain.
Lactic acidosis and hepatotoxicity have happened in some people taking
medicines like BARACLUDE.
In some people, hepatitis B symptoms may get worse or become very serious when
they stop taking BARACLUDE. People should not stop BARACLUDE without talking to
their healthcare provider. Healthcare providers will need to follow their
patients and do blood tests to check the liver when BARACLUDE is stopped.
People should tell their healthcare provider if they have or develop kidney
problems because their healthcare provider may want to do tests to see if a
lower dose is needed or a different dose schedule.
Because BARACLUDE is removed from the body through the kidneys, a lower dose or
a different dose schedule may be required. Healthcare providers may want to
perform tests to determine whether a patient needs a lower dose or should take
BARACLUDE less often than once a day.
It is not known if BARACLUDE is safe to use during pregnancy. It is not known
if BARACLUDE helps to prevent a pregnant mother from passing HBV to her baby. A
pregnant woman and her healthcare provider will need to decide if BARACLUDE is
right for her. A woman should not breastfeed if she is taking BARACLUDE.
People should discuss with their healthcare provider all prescription and
non-prescription medicines, vitamins, herbal supplements, and other health
preparations they are taking or plan to take. BARACLUDE(R) (entecavir) may
interact with medicines that leave the body through the kidneys. The most
common side effects of BARACLUDE in clinical studies were headache, tiredness,
dizziness, and nausea.
This list of side effects is not complete at this time because BARACLUDE is
still under study. People should report any new or continuing symptom to their
healthcare provider. BARACLUDE should be taken once daily on an empty stomach
(at least two hours after a meal and two hours before the next meal). To learn
more about BARACLUDE and for Full Prescribing Information, including boxed
WARNINGS, please visit http://www.bms.com.
Bristol-Myers Squibb is a global pharmaceutical and related health care
products company whose mission is to extend and enhance human life.
BARACLUDE(R) (entecavir) is a trademark of Bristol-Myers Squibb Company.
Bristol-Myers Squibb
http://www.bms.com
ViroPharma
Announces Presentation of Additional HCV-796 Data at Meeting of The European
Association for the Study of the Liver
- Phase 1b
Combination Data Highlight Favorable Tolerability and Additive Antiviral
Activity of HCV-796 -
EXTON, Pa., April 13 /PRNewswire-FirstCall/ -- ViroPharma Incorporated
(Nasdaq: VPHM)
today announced additional data from a Phase 1b study of HCV- 796, a unique,
orally dosed hepatitis C virus (HCV) polymerase inhibitor at the 42nd Annual
Meeting of the European Association for the Study of the Liver (EASL). This
meeting is being held in Barcelona, Spain. These data on the antiviral activity
and tolerability of twice daily HCV-796 in combination with pegylated
interferon alfa-2b (peg-IFN) elaborate on previously presented data. HCV-796 is
currently undergoing Phase 2 evaluation and is being co-developed with Wyeth
Pharmaceuticals, a division of Wyeth (NYSE: WYE).
These Phase 1b combination data demonstrate the additive antiviral
effects of HCV-796 across multiple genotypes of hepatitis C virus, in treatment-naive adult subjects with chronic hepatitis C
infection. HCV-796 dosed twice daily plus peg-IFN
displays clinical antiviral activity that is greater than that of HCV-796 or
peg-IFN alone across all dose cohorts and tested HCV genotypes. Final safety
and tolerability data show that HCV-796 is generally well tolerated when added
to peg-IFN. Adverse events were generally consistent with known effects of
interferons. No dose-limiting toxicities were observed across the range of
HCV-796 study doses.
Phase 1b Clinical Trial Design
This 14 day randomized, double-blind, placebo-controlled,
sequential-group study of ascending multiple doses enrolled subjects with
chronic HCV infection who were naive to treatment. Subjects were enrolled in
sequential, ascending dose cohorts with a target of 16 subjects (12 subjects
receiving HCV-796 BID and 4 receiving placebo in each cohort). The first
cohorts assessed the effect of HCV-796 as monotherapy compared to placebo (data
from which were released on November 10, 2005). Subsequent cohorts were
comprised of subjects who received peg-IFN (PEG-Intron; 1.5 ug/kg/dose) on days
-1 and 7 in combination with either placebo or HCV-796 (100 mg, 250 mg, 500 mg
or 1000 mg) every 12 hours, from days 1 to 14.Antiviral Activity Results
Data are available through treatment day 14 from subjects in four
combination treatment groups (n= 10 to 12 subjects per group) and on 19
subjects who received peg-IFN alone.
-- For genotype 1, mean reduction from baseline ranged from 1.5 to 2.3
log10 on day 7 and from 2.6 to 3.2 log10 on day 14 in the combination therapy
groups compared to 0.9 log10 on day 7 and 1.3 log10 on day 14 for peg-IFN
alone.
-- For non-genotype 1, mean reduction from baseline ranged from 2.8 to
3.5 log10 on day 7 and from 3.5 to 4.8 log10 on day 14 in the combination
therapy groups compared to 1.5 log10 on day 7 and 2.6 log10 on day 14 for
peg-IFN alone.
-- Viral reduction greater or equal to 2.0 log10 at day 14 was achieved
in 70 to 92 percent of subjects in all combination groups compared to 40
percent on peg-IFN alone.
-- At day 14, 30 to 33 percent of patients in the combination groups
receiving greater than or equal to 250 mg BID of HCV-796 achieved viral levels
below the quantification limit of 50 IU/mL HCV RNA.
Safety and
Tolerability Results
A safety review of HCV-796 in combination
with peg-IFN has been completed. Combination therapy including HCV-796 was
found to be generally well tolerated. The observed safety profile supports the
evaluation of HCV-796 in studies of longer duration.
-- Adverse events across all dose cohorts were generally mild to
moderate in severity and were characteristic of the known side effects of
interferons.
-- Adverse events that occurred at a frequency of greater than 15
percent across all dose cohorts of HCV-796 plus peg-IFN and peg-IFN alone
included headache, chills, myalgias, fever, pain, arthralgia and rash.
-- There were two reports of serious adverse events: one in the placebo
arm (pneumonia), and one in the 1000 mg combination cohort (seizure and
rhabdomyolysis in a subject receiving high dose methadone chronically).
-- The rate of discontinuation due to adverse events was low across the
study. No patient discontinued due to adverse events in the 100, 250, or 500 mg
dose cohorts. In the peg-IFN alone group, one patient discontinued due to
hypertension; of those that received 1000 mg HCV-796 plus peg-IFN, three
patients discontinued due to either vasovagal syncope after a blood draw, rash,
or seizure and rhabdomyolysis (in a subject receiving high dose methadone
chronically).
-- No dose-limiting toxicities were identified across the range of study
doses.
Genetic Sequencing
NS5B sequencing was performed on 36 subjects
(11 on peg-IFN alone; 25 HCV- 796 and peg-IFN). Consistent with data from the
Phase 1b study of HCV-796 as monotherapy, the only variant of importance
detected in patients receiving HCV-796 was a C316Y variant known to have
reduced susceptibility to HCV-796. Baseline sequencing did not find any
variation from wild type at this position. The C316Y variant was observed in 7
(28 percent) of patients on HCV- 796 plus peg-IFN, occurring less frequently
than previously seen in patients receiving HCV-796 as monotherapy, and was not
clearly associated with virologic response pattern. The clinical implication of
this mutation, if any, will be evaluated in ongoing and future long-term
studies.
About Hepatitis C
Hepatitis C is a blood-borne virus recognized as a major cause of
chronic hepatitis worldwide. The World Health Organization estimates that 170
million persons worldwide are chronically infected with HCV, and three to four
million persons are newly infected globally each year. According to the U.S.
Centers for Disease Control and Prevention (CDC), about four million people in
the U.S., or 1.8 percent of the population, are infected with HCV.
Currently, there is no specific antiviral agent directed against HCV
that is commercially available, and no vaccine for prevention of HCV infection.
Several interferon (IFN) products are available worldwide, but there are
substantial limitations to the use of these products when given as monotherapy
or in conjunction with ribavirin in the treatment of chronic HCV infection. In
addition to the relatively poor treatment response in patients infected with
genotype 1 HCV, the most common strain in the U.S., Western Europe and Japan,
the considerable side effects frequently associated with the use of IFN can
lead to discontinuation of therapy in approximately 20 percent of patients.
About ViroPharma Incorporated
ViroPharma Incorporated is committed to the development and
commercialization of products that address serious diseases treated by
physician specialists and in hospital settings. ViroPharma commercializes
Vancocin(R), approved for oral administration for treatment of
antibiotic-associated pseudomembranous colitis caused by Clostridium difficile
and enterocolitis caused by Staphylococcus aureus, including
methicillin-resistant strains (for prescribing information, please download the
package insert at http://www.viropharma.com/docs/pulvules_pi.pdf ).
ViroPharma currently focuses its drug development activities in viral
diseases including cytomegalovirus (CMV) and hepatitis C (HCV). For more
information on ViroPharma, visit the company's website at http://www.viropharma.com .SOURCE
ViroPharma Incorporated