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Alan Franciscus
Editor-in-Chief
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In This Issue:
• Rigel
Initiates Phase I/II Trial of R803 For The Treatment Of Hepatitis
C Virus
• Hepatitis B Antenatal Screening Program
in Amsterdam
• Vertex Pharmaceuticals Announces Plans
for the METRO Study: Triple Combination of Merimepodib, Pegasys(R)
and Copegus(R) in Hepatitis C Patients
• Newly Published Study Investigates Pegasys
(peginterferon alfa-2a) and Copegus (ribavirin, USP) for the
Treatment of Chronic Hepatitis C In Black Americans
• African-Americans Respond Poorly to Hepatitis
C Treatment
• Anadys Pharmaceuticals Announces Selection
of ANA975 As A Development Candidate For Front-Line Treatment
Of Chronic Hepatitis C
• SciClone Announces Collaboration To Develop
Pegylated Zadaxin
• Human Genome Sciences Initiates Phase
2 Clinical Trial Of Albuferon(TM) For The Treatment Of Chronic
Hepatitis C
• Characteristics and Survival in Hepatocellular
Carcinoma
May 24th, 2004
Rigel Initiates Phase I/II Trial of R803
For The Treatment Of Hepatitis C Virus
Source: PRNewswire
Hepatitis C Virus Affects an Estimated
170 Million People Worldwide, with Three to Four Million New
Infections Every Year
SOUTH SAN FRANCISCO, Calif. -- Rigel Pharmaceuticals,
Inc. (Nasdaq: RIGL) today announced the initiation of a multi-dose
Phase I/II clinical trial for R803, an experimental drug to
treat the blood-borne liver disease Hepatitis C Virus (HCV).
The goals of this trial are to assess safety, tolerability
and pharmacokinetics of multiple dose administrations of R803
in patients with HCV. The trial will also explore the effectiveness
of various dosing regimens of R803 in reducing viral levels.
Results of this trial are expected by the fourth quarter of
2004 and will allow Rigel to enter into the broader, longer-term
trials, which are necessary for FDA approval.
The Phase I/II multi-dose clinical trial
is a double-blind, placebo- controlled, dose-ascending study
in subjects with diagnosed HCV. There will be eight groups
of subjects, with each subsequent group receiving an increasing
dose or increasing number of days of treatment. Subjects will
be dosed for two to four days, plus the morning dose on the
following day. In January, Rigel released the results of a
Phase I clinical trial, which evaluated the safety of R803
in healthy volunteers. No clinically adverse effects were
attributed to R803 during this trial at relevant dose levels.
"HCV is a serious global epidemic,
and since the current therapies have significant limitations,
new therapies are needed to treat this infection," commented
Elliott B. Grossbard, M.D., Senior Vice President, Medical
Development of Rigel. "Rigel's R803 represents a novel
approach in the treatment of HCV, and is one of the first
direct antiviral agents to reach human clinical trials."
"Because of its unique mechanism of
action, Rigel's R803 has great promise as a potential therapeutic
in the fight against HCV," noted Donald G. Payan, M.D.,
Chief Scientific Officer and Executive Vice President of Rigel.
"Rigel is committed to the development of this compound
and to furthering treatment options for those affected by
HCV."
Rigel's R803, a non-nucleoside HCV polymerase
inhibitor, is an oral, small-molecule compound. To date, R803
has demonstrated potent efficacy in inhibiting viral replication
in cell-based assay systems and in live virus assays. In these
models, R803 has been shown to be active against various genotypes
of HCV, including genotype 1, the most common in North America
and Europe. In various assays, R803 appears to act within
days to reduce viral levels significantly. In addition, as
a result of R803's novel viral binding site, resistance may
be slow to develop. In cell-based systems, R803 has demonstrated
synergy when used with interferon alpha (IFN). This observation
may allow the use of a reduced dose of IFN, potentially minimizing
the significant side effects of that drug.
HCV: Current Treatments and Market
Opportunity
Hepatitis C is an inflammation of the liver caused by HCV.
As the most common blood-borne infection in the U.S., HCV
affects approximately 4 million Americans and 170 million
individuals worldwide. Approximately 80 percent of those with
acute illness will go on to develop chronic hepatitis, a condition
that has been linked to cirrhosis, hepatocellular carcinoma
(liver cancer) and liver failure. HCV accounts for 30 percent
of end-stage liver disease and liver cancer and is the leading
cause of liver failure, which can result in the need for liver
transplantation. Public health officials in the U.S. and abroad
have mobilized to address this medical crisis by identifying
detection guidelines for HCV and implementing therapies to
eradicate chronic infection.
Currently available HCV therapies are only
modestly effective at treating the disease. The most prevalent
treatment regimen utilizes IFN, usually in combination with
ribavirin. IFN shows only a 20 to 40 percent success rate
in patients who complete therapy, with significant side effects
resulting in up to half the patients either quitting treatment
or moving to a lower dose regimen. Moreover, IFN is least
effective against HCV genotype 1, the strain responsible for
70 percent of chronic HCV infection cases in the U.S. Rigel
believes that its approach is substantially different from
that of IFN; instead of working to boost the immune system,
experiments indicate that R803 directly, rapidly, selectively
and potently targets HCV by interfering with a viral polymerase
protein that is needed for replication.
With the current high prevalence and projected
increase in cases of HCV and related diseases, and with the
limited success of currently available therapies, Rigel believes
that the potential for new direct HCV therapeutics is large
and that R803 has the potential to be at the forefront of
this opportunity.
About Rigel
Rigel's mission is to become a source of novel, small-molecule
drugs to address large, unmet medical needs. We have initiated
three development programs: asthma/allergy, hepatitis C and
rheumatoid arthritis. Rigel has begun clinical testing of
its first two product candidates, R112 for allergic rhinitis
and R803 for hepatitis C, and expects to begin clinical trials
of R406 for the treatment of rheumatoid arthritis by the end
of 2004, to be followed by clinical trials for drug candidates
in asthma and oncology (www.rigel.com).
This press release contains "forward-looking"
statements, including statements related to Rigel's plans
to pursue clinical development of product candidates and the
timing thereof and the potential efficacy of product candidates.
Any statements contained in this press release that are not
statements of historical fact may be deemed to be forward-looking
statements. Words such as "plans," "intends,"
"expects" and similar expressions are intended to
identify these forward-looking statements. There are a number
of important factors that could cause Rigel's results to differ
materially from those indicated by these forward-looking statements,
including risks associated with the timing and success of
clinical trials and the commercialization of product candidates,
as well as other risks detailed from time to time in Rigel's
SEC reports, including its Annual Report on Form 10-K for
the year ended December 31, 2003, and its Quarterly Report
on Form 10-Q for the quarter ended March 31, 2004. Rigel does
not undertake any obligation to update forward-looking statements.
Back to top
May 25th, 2004
Hepatitis
B Antenatal Screening Program in Amsterdam
Source: www.gastrohep.com
Tracing and immunizing susceptible contacts
of women screened for hepatitis B virus, should be an integral
part of a control program, find researchers in the June issue
of the Journal of Hepatology.
Hepatitis B control in Europe concentrates
on antenatal screening to reduce vertical transmission.
In an attempt to reduce horizontal transmission
and the pool of infectious individuals, the health authorities
in Amsterdam integrated the tracing and immunizing of contacts
in the antenatal screening program.
In this study, researchers from the Netherlands
evaluated this public health program between 1992 and 1999.
In the program, all contacts are tested
for serological markers of previous infection. Vaccination
is offered to susceptible contacts.
In addition, chronically infected contacts
are counseled and referred for treatment if justified. 94%
of contacts completed the vaccination series.
Journal of Hepatology
Overall, the researchers found that for
738 women testing positive for the hepatitis B surface antigen,
1219 contacts were reported.
Of the 1219 contacts, 90% participated.
The team found that 43% had serological markers of previous
infection and of these, 25% were infectious.
There were 603 eligible contacts. Of these,
94% completed the vaccination series.
The research team determined that country
of origin was an independent predictor of contact participation
and compliance with completion of the vaccination series.
They found that postvaccination titers
for antibodies against the surface antigen were below 10IU/L
in 5% of contacts under 30 and in 12% of those over 30.
Dr Jim van Steenbergen and colleagues concluded,
"Tracing and immunizing susceptible contacts of women
screened as HBsAg-positive, should be an integral component
of any country's HBV control program".
J Hepatol 2004; 40(6): 979-85
Back to top
Vertex
Pharmaceuticals Announces Plans for the METRO Study: Triple
Combination of Merimepodib, Pegasys(R) and Copegus(R) in Hepatitis
C Patients
Source: PRNewswire
-- Roche Agrees to Provide Pegasys
and Copegus for Phase IIb Clinical Trial --
Cambridge, Mass.-- Vertex Pharmaceuticals
Incorporated (Nasdaq: VRTX) announced today the design of
a Phase IIb clinical study that it plans to conduct with merimepodib,
an investigational oral therapy for the treatment of hepatitis
C virus (HCV) infection, in patients who are non-responders
to prior treatment with pegylated interferon (peg-IFN) and
ribavirin. The clinical trial will be conducted at centers
in the United
States and is expected to enroll approximately
315 patients who will receive merimepodib or placebo in combination
with Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin).
Roche will provide Pegasys and Copegus to Vertex for use in
this study, providing support for the clinical development
of merimepodib as an investigational agent that may enhance
the antiviral activity of Pegasys and Copegus, which is the
most frequently prescribed treatment combination for HCV infection
in the United States. As part of the supply agreement with
Roche, Vertex will share data and data analysis with Roche
at predetermined intervals during the course of the study.
Vertex owns worldwide development and commercialization rights
to merimepodib.
"HCV-infected patients who do not
respond to initial combination therapy with pegylated interferon
plus ribavirin face limited treatment options and the prospect
of worsening liver disease," stated John J. Alam, M.D.,
Senior Vice President of Drug Evaluation and Approval at Vertex.
"Preclinical and clinical data reported to date for merimepodib,
Vertex's lead oral therapy for HCV infection, have highlighted
the potential for this drug candidate to enhance the standard
of care in hepatitis C. In this Phase IIb clinical trial,
we will seek to evaluate the ability of a triple combination
of merimepodib plus peginterferon alfa-2a and ribavirin to
increase viral clearance in patients who are refractory to
prior combination treatment."
Merimepodib Triple Combination Study (The METRO Study)
The MErimepodib TRiple cOmbination study (the METRO study)
has been designed as a double-blind, placebo-controlled, randomized
Phase IIb study, with a goal of evaluating the antiviral activity
of two doses of merimepodib (MMPD) in combination with Pegasys
and Copegus. Vertex anticipates that the trial will enroll
approximately 315 patients who were previously non-responders
to combination therapy, defined as at least 12 weeks of prior
pegylated interferon-alfa and ribavirin treatment without
having achieved undetectable HCV-RNA (< 50 I.U.) at any
timepoint. The trial is designed so that patients will be
treated with 50 mg MMPD, 100 mg MMPD, or placebo twice daily
in combination with standard doses of Pegasys and Copegus
for an initial period of 24 weeks. At the end of 24 weeks,
patients with undetectable HCV-RNA will receive combination
therapy with Pegasys and Copegus, only, for an additional
24 weeks. Patients completing the 48-week treatment period
will be followed for an additional 24-week treatment-free
period. The study is expected to involve more than 40 clinical
centers and will be conducted in the United States. Study
site selection is underway, and the first centers are expected
to begin enrolling patients in the third quarter of 2004.
The goal of the METRO study will be to
evaluate the safety, pharmacokinetics and efficacy of MMPD
in combination with pegylated interferon. The primary endpoint
of the study is to evaluate the antiviral activity of MMPD
and perform an assessment of the proportion of MMPD-treated
patients who achieved a sustained virologic response (SVR)
compared to placebo at week 72 (end of follow-up). Secondary
endpoints include evaluation of the antiviral activity of
MMPD-treated patients at 12, 24, and 48 weeks. The doses and
duration of MMPD treatment in this study have been selected
based on comprehensive analysis of the relationship between
plasma exposure and antiviral effect in previous clinical
studies of merimepodib, as well observations from previous
clinical studies that suggest that merimepodib enhances the
antiviral activity of combination therapy primarily in the
first 24 weeks of treatment.
About Merimepodib and HCV
Merimepodib is a small molecule, orally administered inhibitor
of the enzyme inosine monophosphate dehydrogenase (IMPDH).
IMPDH inhibition leads to a reduction in intracellular guanosine
triphosphate (GTP), a molecule required for DNA and RNA synthesis.
Six-month results from a Phase II study presented at the Annual
Meeting for the European Association for the Study of the
Liver (EASL) demonstrated that relative to placebo treatment,
merimepodib treatment produced a statistically significant,
dose-dependent increase in the percentage of treatment-refractory
patients with HCV genotype 1 who achieved undetectable levels
of HCV-RNA at six months. Recent reports in the medical literature
suggest that IMPDH inhibitors such as merimepodib may enhance
the antiviral activity of ribavirin in vitro by depleting
GTP and increasing the rate of incorporation of ribavirin
into viral RNA, rendering the virus nonfunctional. The antiviral
activity observed clinically when merimepodib is added to
ribavirin-containing HCV therapies is consistent with these
preclinical findings. In combination with the standard of
care, MMPD may help to increase the sustained viral response
rate in HCV patients, the principal goal of treatment.
Chronic hepatitis C virus (HCV) infection
is a serious public health concern affecting approximately
2.7 million people in the United States. HCV causes inflammation
of the liver, which may lead to fibrosis and cirrhosis, liver
cancer, and ultimately, liver failure. Cirrhosis of the liver
resulting from chronic HCV infection is the leading indication
for liver transplantation in the U.S. Due to the asymptomatic
nature of HCV infection, it often goes undetected for up to
20 years following initial infection. Worldwide, the disease
strikes as many as 185 million people. Each year, 8,000 to
10,000 people in the U.S. die from complications of HCV.
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 partners. Vertex's
product pipeline is principally focused on viral diseases,
inflammation, autoimmune diseases and cancer.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's
leading innovation-driven healthcare groups. Its core businesses
are pharmaceuticals and diagnostics. Roche is number one in
the global diagnostics market, the leading supplier of pharmaceuticals
for cancer and a leader in virology and transplantation. As
a supplier of products and services for the prevention, diagnosis
and treatment of disease, the Group contributes on a broad
range of fronts to improving people's health and quality of
life. Roche employs roughly 62,000 people in 150 countries.
The Group has alliances and research and development agreements
with numerous partners, including majority ownership interests
in Genentech and Chugai.
This press release may contain forward-looking
statements, including statements that (i) merimepodib holds
promise as part of combination therapy for HCV patients who
have limited treatment options and represents an attractive
commercial opportunity for Vertex; and (ii) a Phase IIb clinical
study of merimepodib will be initiated in the second half
of 2004. 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 Vertex's
actual results to vary materially. These risks and uncertainties
include, among other things, the risks that clinical trials
for merimepodib may not be initiated or, if initiated, may
not proceed as planned due to technical, scientific, or patient
enrollment issues, that results from planned clinical trials
with merimepodib will not reflect the positive results from
earlier trials, that positive nonclinical study results for
merimepodib will not be duplicated in future nonclinical or
clinical studies and other risks listed under Risk Factors
in Vertex's form 10-K filed with the Securities and Exchange
Commission on March 15, 2004.
Lexiva(TM) is a registered trademark of the GlaxoSmithKline
group of companies.
Vertex's press releases are available at
www.vrtx.com.
Vertex Contacts:
Lynne Brum, VP, Corporate Communications and Financial Planning
(617) 444-6614
Michael Partridge, Director, Corporate Communications (617)
444-6108
Lora Pike, Manager, Investor Relations (617) 444-6755
SOURCE Vertex Pharmaceuticals Incorporated
CONTACT: Lynne Brum, VP, Corporate Communications
and Financial
Planning, +1-617-444-6614, or Michael Partridge, Director,
Corporate
Communications, +1-617-444-6108, or Lora Pike, Manager, Investor
Relations,
+1-617-444-6755 all of Vertex
First Call Analyst:
FCMN Contact: marion_marks@vrtx.com
Company News On-Call: http://www.prnewswire.com/comp
/938395.html/
Web site: http://www.vrtx.com/
(VRTX)
Back to top
Newly
Published Study Investigates Pegasys (peginterferon alfa-2a)
and Copegus (ribavirin, USP) for the Treatment of Chronic
Hepatitis C In Black Americans
Source: Company Press Release
Authors state: “To date, this
is the highest response rate to treatment observed in a black
population” -
New York, NY – A study published
in the June issue of Hepatology showed that 26 percent
of black Americans with chronic hepatitis C treated with the
most prescribed hepatitis C therapy in the U.S., a combination
of Pegasys (peginterferon alfa-2a), a pegylated interferon,
and Copegus (ribavirin, USP), an anti-viral medication, achieved
a sustained virological response (SVR).
Sustained virological response refers to
a patient’s continued undetectable serum hepatitis C
RNA levels 24 weeks after finishing a course of treatment.
The primary objective of the study was to investigate the
efficacy, safety and tolerability of Pegasys combination therapy
in non-Hispanic black Americans with genotype 1 hepatitis
C virus (HCV), the strain of the virus that is most difficult
to treat. In the article, the authors of the study state:
“In summary, we have shown that 48 weeks of therapy
with peginterferon alfa-2a and ribavirin results in an SVR
in 26 percent of blacks chronically infected with HCV genotype
1. To date, this is the highest response rate to treatment
observed in a black population.” In black patients who
completed 48 weeks of treatment, 32 percent achieved an SVR.
“Historically, black Americans infected
with hepatitis C have been underrepresented in clinical trials,”
said Lennox Jeffers, MD, professor of medicine at the University
of Miami School of Medicine and chief of Hepatology at the
Miami VA Medical Center. “These results are very encouraging
and have already led to a large National Institutes of Health
(NIH) study involving 400 patients in eight centers throughout
the United States to examine viral hepatitis C resistance
in the black American population.”
Hepatitis C is a blood-borne virus that
chronically infects an estimated 2.7 million Americans. It
can cause progressive liver injury and lead to fibrosis and
eventually cirrhosis. Black Americans have the highest prevalence
rates for hepatitis C among all racial and ethnic groups in
the U.S. and hepatitis C treatment has historically been less
effective in this population.
“The results of this study provide
promising information for black Americans infected with hepatitis
C,” said Charles Howell, MD, associate professor in
the Department of Medicine and director of Hepatology Research
at the University of Maryland School of Medicine, and one
of the lead investigators in the study. “Until now,
the efficacy of peginterferon plus ribavirin for hepatitis
C treatment in black Americans was unclear. This new data
establishes the efficacy and safety of peginterferon alfa-2a
(Pegasys) and ribavirin for African Americans infected with
genotype 1, the most common variant of hepatitis C in the
United States.”
Study Design
The open-label noncomparative study was conducted at eleven
sites in the United States and included 78 black patients
and 28 white patients.
All patients were interferon-naïve
with chronic hepatitis C genotype 1 and elevated ALT levels.
Patients received 180 mcg subcutaneously of Pegasys, once
weekly, along with either 1000 or 1200 mg/day of Copegus,
depending on their weight, for 48 weeks, with 24 weeks of
treatment-free follow-up. Early virological response (EVR)
was assessed at 12 weeks of therapy and SVR at week 72.
This trial included a relatively small
cohort of patients receiving treatment. Studies with larger
patient populations are currently underway to confirm the
findings from this study.
The SVR rate in white patients in the study
was 39 percent, with a confidence interval of 21 to 57 percent.
Conclusions should not be drawn in the white patient population
because of the small number (n=28) in the study. In previous
studies, more than half of patients with genotype 1 hepatitis
C achieved a sustained virological response after 48 weeks
of treatment with Pegasys combination therapy.
Histological Response
Paired liver biopsies were obtained from 53 of the black patients
and 16 of the white patients. In these patients, more than
90 percent in both groups showed either improvement or stabilization
of fibrosis (scar tissue in the liver). Improvements in fibrosis
score occurred in 25 percent of all patients (13 of 53 patients).
Adverse Events
Adverse events were similar to those seen in Pegasys and Copegus
registration trials. Incidence rates for AEs among the white
patient and black patient groups included: fatigue (71 percent
vs. 60 percent), headache (82 percent vs. 54 percent), rigors
(35 percent vs. 32 percent), insomnia (50 percent vs. 27 percent),
rash (26 percent vs. 18 percent), and nausea (54 percent vs.
23 percent). Five percent of black patients and fourteen percent
of white patients withdrew prematurely due to adverse events
or laboratory abnormalities. Black patients had lower baseline
absolute neutrophil counts compared to white patients. Dose
modifications of Pegasys (withheld or reduced) occurred among
46 percent of black patients and 29 percent of white patients;
the most common cause was neutropenia (37 percent among black
patients and 18 percent among white patients).
About Pegasys
Pegasys, a pegylated alpha interferon, and Copegus, an oral
antiviral, were approved by the FDA in December 2002 for use
in combination for the treatment of adults with chronic hepatitis
C who have compensated liver disease and have not previously
been treated with interferon alpha. Patients in whom efficacy
was demonstrated included patients with compensated liver
disease and histological evidence of cirrhosis.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is
the U.S. prescription drug unit of the Roche Group, a leading
research-based health care enterprise that ranks among the
world’s leaders in pharmaceuticals, diagnostics and
vitamins. Roche discovers, develops, manufactures and markets
numerous important prescription drugs that enhance people's
health, well-being and quality of life. Among the company’s
areas of therapeutic interest are: dermatology; genitourinary
disease; infectious diseases, including influenza; inflammation,
including arthritis and osteoporosis; metabolic diseases,
including obesity and diabetes; neurology; oncology; transplantation;
vascular diseases; and virology, including HIV/AIDS and hepatitis
C.
For more information on the Roche pharmaceuticals business
in the United States, visit the company’s web site at:
http://www.rocheusa.com
Back to top
African-Americans
Respond Poorly to Hepatitis C Treatment
Duke University Medical Center
Durham, N.C. - African-Americans have a
significantly lower response rate to treatment for chronic
hepatitis C than non-Hispanic whites, according to a new study
led by Duke University Medical Center researchers.
Some African-Americans - 19 percent - did
respond to the drug combination of peginterferon alfa-2b and
ribavirin. But in non-Hispanic whites with the same disease,
the hepatitis C genotype 1 virus strain, 52 percent had no
evidence of the virus in their blood six months after completing
the drug therapy - one of the highest response rates ever
reported for this therapy.
The study showed the difference in infection
rates between the two groups is not responsible for the low
response rate to treatment in African-Americans.
"This study definitively proves that
the difference in response rate is not due to the higher rate
of genotype 1 infection in African-Americans," said Andrew
Muir, M.D., lead author of the study and an assistant professor
of medicine at Duke University Medical Center. The results
were published May 27, 2004, in the New England Journal
of Medicine.
Muir recommends African-Americans consult
their physicians about the decision to receive treatment for
hepatitis C.
"These results should be discussed
with African-American patients with hepatitis C. However,
we must also let patients know that some African-Americans
did respond to therapy, and African-American patients should
continue to be considered for treatment," said Muir,
a gastroenterologist.
The prospective study followed 100 African-American
and 100 non-Hispanic white chronic hepatitis C patients during
48 weeks of drug treatment. The majority of both patient groups,
98 percent, had hepatitis C genotype 1, which has a lower
response rate to treatment than other hepatitis C genotypes.
This virus strain is the most common form of the hepatitis
C in the United States and is the most difficult to treat,
Muir said. An estimated 4 million people in the United States
are infected with hepatitis C.
African-Americans have a higher rate of
genotype 1 infection than non-Hispanic whites. Earlier studies
had suggested the prevalence of genotype 1 infection in African-Americans
was responsible for their lower response rate to treatment,
because the virus strain is difficult to treat.
By comparing similar patient groups, the
researchers determined that the difference in infection rates
does not explain the lower response rate to treatment among
African-Americans.
Statistical analyses of characteristics
such as sex, age, weight, level of education, duration of
infection and other medical conditions showed race was the
only variable associated with a significant difference in
response to treatment. In addition, side effects and tolerance
of the medications were similar in both groups.
"The reasons for the lower response
in African Americans are still unclear. We need further research
to better understand the reason for the lower response rate,"
Muir said.
Patients were drawn from the community
and seen in clinical practice by members of the Atlantic Coast
Hepatitis Treatment Group, which includes 16 centers in North
Carolina, South Carolina, Virginia and Tennessee. The baseline
characteristics of both groups were similar. The study was
supported by Schering-Plough, manufacturer of the drug combination
therapy.
The drug treatment goal was a sustained
virologic response, which means the patient has no detectable
hepatitis C virus in blood tests six months after treatment
ends. Both groups were treated with peginterferon alfa-2b
and ribavirin. Peginterferon is an injectable, long-acting
form of interferon, a synthetic version of immune system substance
produced by the body to help fight infections. Patients received
a dose of peginterferon alfa-2b every week. Ribavirin is an
oral antiviral drug; patients took the drug every day in pill
form.
Muir has received an American Association
for the Study of Liver Diseases/Schering-Plough Advanced Hepatology
Fellowship. He has also received grant support from Schering-Plough
and has served as a paid speaker for Schering-Plough.
Back to top
May 26th, 2004
Anadys
Pharmaceuticals Announces Selection of ANA975 As A Development
Candidate For Front-Line Treatment Of Chronic Hepatitis C
Source: Business Wire
Anadys Designates ANA975, an Oral Prodrug
of Isatoribine
San Diego-- Anadys Pharmaceuticals, Inc.
(Nasdaq:ANDS) today announced it has selected ANA975, an oral
prodrug of isatoribine (ANA245), to be its development candidate
for front-line treatment of chronic hepatitis C virus (HCV)
infection. ANA975 builds from Anadys' clinical experience
with isatoribine, including knowledge of isatoribine doses
that have been shown to be well-tolerated in Phase 1A and
Phase 1B trials and that demonstrated a statistically significant
reduction of HCV viral load. Anadys expects that this knowledge
will facilitate an accelerated and efficient clinical development
program for ANA975.
"ANA975 was selected from the ANA97X
family of isatoribine prodrug compounds based upon its favorable
pharmaceutical properties, which we believe should allow it
to become an orally administered front-line treatment for
chronic HCV," said Devron Averett, Ph.D., Senior Vice
President of Drug Development for Anadys.
ANA975 is an oral prodrug of isatoribine.
Prodrugs are distinct chemical entities that are administered
as a precursor of the active drug and then are converted into
the active drug in the body. Isatoribine and its prodrugs
are a new class of drugs being developed by Anadys to regulate
innate immunity, the body's first line of defense against
viruses and other foreign organisms. Anadys believes that
isatoribine interacts with a specific receptor on certain
immune system cells named TLR-7, which assists in regulating
innate immune responses against viruses.
Interim results from a Phase IB clinical
trial showed isatoribine to be safe and well-tolerated at
all doses tested. Although long term therapeutic utility was
not a stated objective of the Phase IB clinical trial, at
the 800 mg dose level the viral load difference between the
beginning and end of treatment was statistically significant
(p=0.03), with a median change in viral load from baseline
of -0.94 log10 units. Anadys is encouraged by these early
results, and believes they provide proof of concept that a
compound interacting with TLR-7 can reduce viral load in HCV
infected patients.
"We are very pleased in achieving
one of our goals for the second quarter of 2004, by selecting
a front-line clinical candidate for the treatment of chronic
hepatitis C virus infection," said Kleanthis G. Xanthopoulos,
Ph.D., President and CEO of Anadys.
"ANA975 broadens our existing pipeline
of anti-infective drug candidates, which includes isatoribine
and ANA971 for the treatment of HCV, ANA380 for the treatment
of hepatitis B virus, and preclinical candidates to treat
bacterial infections. We look forward to advancing ANA975
into the clinic."
About isatoribine (ANA245)
Isatoribine is a nucleoside analog Anadys is evaluating in
ongoing clinical trials for the treatment of HCV infections.
Isatoribine represents one of a new class of drugs being developed
by Anadys to regulate innate immunity, combat HCV infection,
and overcome limitations of current anti-HCV therapies. Anadys
believes isatoribine interacts with a specific receptor, Toll-like
receptor 7, or TLR-7, that is present on certain immune system
cells. Although results of initial clinical trials may not
be predictive of future results, interim results of the Phase
1B clinical trial show that isatoribine is biologically active
in adults with chronic HCV infection and results from dosing
a cohort of six HCV infected patients with 800mg of isatoribine
showed a statistically significant reduction of viral load
(p=0.03) at the end of one week, with a median change in viral
load from baseline of -0.94 log10 units. Anadys is currently
recruiting patients for an isatoribine Phase I/II study.
About hepatitis C
Hepatitis C virus, the most common chronic blood-borne infection
in the United States, causes inflammation of the liver and
may progress to more serious complications such as cirrhosis
of the liver, liver cancer and death. Approximately 2.7 million
people in the United States are chronically infected with
HCV, and the Centers for Disease Control (CDC) estimates that
by the year 2010, the number of deaths attributed annually
to HCV could surpass that due to HIV/AIDS. Worldwide sales
for anti-infective products were $40 billion in 2002, yet
current treatments for HCV may be ineffective in up to 50%
of patients due to the development of drug-resistant viral
strains, and many treatments are associated with serious side
effects.
About Anadys Pharmaceuticals, Inc.
Anadys Pharmaceuticals, Inc. (www.anadyspharma.com)
is a biopharmaceutical company committed to advancing patient
care by discovering, developing and commercializing novel
small molecule, anti-infective medicines for the treatment
of hepatitis C virus, hepatitis B virus and bacterial infections.
Anadys is advancing its anti-infective portfolio through the
development of its two clinical programs, the isatoribine
family of compounds and ANA380. In addition, Anadys' anti-infective
therapeutic platform is designed to advance a strong and continual
pipeline of drug candidates into the clinic.
Safe Harbor Statement
Statements in this press release that are not strictly historical
in nature constitute "forward-looking statements."
Such statements include, but are not limited to, references
to the biological activity of isatoribine in HCV infected
patients, viral load reduction resulting from administration
of isatoribine to HCV infected patients, the believed mechanism
of action of isatoribine and its effect on a patient's immune
system, the favorable pharmaceutical properties of ANA975,
the potential for ANA975 to become an orally administered
front-line treatment for chronic HCV and expectations regarding
the timing and duration of further clinical trials of isatoribine
and ANA975. Such forward-looking statements involve known
and unknown risks, uncertainties and other factors which may
cause the actual results of Anadys Pharmaceuticals to be materially
different from historical results or from any results expressed
or implied by such forward-looking statements. In particular,
the results of initial clinical trials are not necessarily
predictive of future results, and Anadys can provide no assurances
that isatoribine or ANA975 will have favorable safety, tolerability
or efficacy results in later clinical trials, or receive regulatory
approval. In addition, Anadys' results may be affected by
competition from other biotechnology and pharmaceutical companies,
its effectiveness at managing its financial resources, its
ability to successfully develop and market products, difficulties
or delays in its clinical trials, difficulties or delays in
manufacturing its clinical trials materials, the scope and
validity of patent protection for its products, regulatory
developments involving future products and its ability to
obtain additional funding to support its operations. These
and other factors that may cause actual results to differ
are more fully discussed in the "Risk Factors" section
of Anadys' Form 10-Q for the quarter ended March 31, 2004.
All forward-looking statements are qualified in their entirety
by this cautionary statement. Anadys is providing this information
as of this date and does not undertake any obligation to update
any forward-looking statements contained in this document
as a result of new information, future events or otherwise.
Back to top
SciClone
Announces Collaboration To Develop Pegylated Zadaxin
Source: Business Wire
San Mateo, CA --SciClone Pharmaceuticals,
Inc. (Nasdaq:SCLN) today announced that it has entered into
a collaborative agreement with Nektar Therapeutics' (Nasdaq:NKTR)
subsidiary, Nektar Therapeutics, AL Corporation to develop
a pegylated formulation of ZADAXIN(R). Nektar will apply its
Advanced PEGylation technology to ZADAXIN with the objective
of improving the therapeutic use and potential efficacy of
the compound. SciClone has filed for worldwide patent protection
for the composition-of-matter of pegylated ZADAXIN.
Dr. Cynthia Tuthill, Vice President of
Scientific Affairs at SciClone commented, "We are very
pleased to be working with Nektar, a recognized leader in
the field of pegylation technology, on this significant initiative."
If the formulation is successful, pegylated ZADAXIN could
lead to improved patient compliance due to less frequent dosing
and would allow the drug to remain in the body at a higher
concentration level for a longer period of time. In addition
to potentially enhancing the use of ZADAXIN in the treatment
of hepatitis C and hepatitis B, SciClone believes that a pegylated
formulation also could broaden the potential application of
ZADAXIN in cancer therapy.
About Nektar Advanced PEGylation
Nektar Advanced PEGylation, developed by Shearwater, now part
of Nektar, is based on the use of non-toxic polyethylene glycol
(PEG) polymers, which can be attached to most major drug classes,
including proteins, peptides, antibody fragments, small molecules,
and other drugs. Nektar Advanced PEGylation has the potential
to improve the safety and efficacy of therapeutic agents by
increasing drug circulation time in the bloodstream, increasing
bioavailability, decreasing immunogenicity, decreasing dosing
frequency, and improving drug solubility and stability.
About SciClone
SciClone Pharmaceuticals is a biopharmaceutical company engaged
in the development of therapeutics to treat life-threatening
diseases. SciClone is currently evaluating its lead product
ZADAXIN in several clinical trials, including two phase 3
hepatitis C clinical trials in the U.S., a completed phase
3 hepatitis B clinical trial in Japan, a phase 2 malignant
melanoma clinical trial in Europe, two phase 2 liver cancer
pilot studies in the U.S., a hepatitis C triple therapy open-label
clinical trial in Mexico, and a hepatitis B combination therapy
trial in Taiwan. SciClone recently announced plans for a ZADAXIN
phase 3 hepatitis C triple therapy clinical trial in Europe.
The Company's other principal drug development candidate is
SCV-07, a potentially orally available therapeutic to treat
viral and infectious diseases. For more information about
SciClone, visit www.sciclone.com.
About Nektar Therapeutics
Nektar Therapeutics provides industry-leading drug delivery
technologies, expertise and manufacturing to enable the development
of high-value, differentiated therapeutics. Nektar's advanced
drug delivery capabilities are designed to enable the company's
biotechnology and pharmaceutical partners to solve drug development
challenges and realize the full potential of their therapeutics,
from developing new molecular entities to managing the life
cycles of established products.
Back to top
Human
Genome Sciences Initiates Phase 2 Clinical Trial Of Albuferon(TM)
For The Treatment Of Chronic Hepatitis C
Source: PRNewswire
Rockville, MD -- Human Genome Sciences,
Inc. (Nasdaq: HGSI) announced today that it has begun dosing
patients in a Phase 2 clinical trial of Albuferon(TM) (albumin-interferon
alpha) in patients with chronic hepatitis C who are naive
to interferon-alpha treatments.
The Phase 2 trial is a randomized, open-label,
multi-center, parallel- design dose-ranging study to evaluate
the safety, tolerability, pharmacology, and optimal dosing
of Albuferon.
The Phase 2 clinical trial will be conducted
in Canada, and will enroll approximately forty patients with
hepatitis C virus (HCV) genotype 1. Genotype 1 accounts for
nearly seventy percent of all HCV infections in North America
and is generally regarded as the most difficult HCV genotype
to treat. A minimum of ten patients will be randomized to
each of three dose groups, which will be given two doses of
Albuferon administered subcutaneously fourteen days apart.
The pharmacodynamic activity of Albuferon will be evaluated
based on HCV RNA viral load reductions over a 28-day period
of exposure and early virologic response at Day 28. One of
the study objectives is to identify a range of active doses
that Human Genome Sciences plans to evaluate in a larger 48-week
study of Albuferon in combination with ribavirin in patients
with HCV genotype 1 who are naive to interferon treatments.
Interim results of an ongoing Phase 1/2
clinical trial of Albuferon in interferon-experienced adults
with chronic hepatitis C were presented at the April 2004
Annual Meeting of the European Association for the Study of
the Liver (EASL) in Berlin.(1) Interim results demonstrate
that Albuferon is well tolerated, has a prolonged half-life,
and is biologically active. On average, patients participating
in the ongoing clinical trial had been treated previously
for approximately 68 weeks with regimens containing interferon
alpha or pegylated interferon. Data were presented at the
EASL meeting on fifty-one patients who were enrolled under
an amendment to the original protocol and were treated with
single doses of Albuferon administered subcutaneously at 120
micrograms (mcg), 180 mcg, 240 mcg, 320 mcg, 400 mcg, 500
mcg, or 600 mcg -- or with two doses of Albuferon administered
subcutaneously fourteen days apart at 400 mcg or 500 mcg.
All cohorts treated under the amended protocol showed evidence
of biological activity. Viral load levels represent the quantity
of hepatitis C virus in the blood, and reductions in viral
load are a surrogate marker for clinical benefit. Fifty- five
percent (28/51) of Albuferon-treated patients in the combined
single- injection and double-injection cohorts experienced
an antiviral response, as demonstrated by reductions in their
viral load of 0.5 log or greater at two consecutive time points.
Of those experiencing an antiviral response, seventy-nine
percent (22/28) experienced reductions of at least 0.9 log
units.
Vijayan Balan, M.D., a lead investigator
and Director, Hepatobiliary Clinic, Division of Transplant
Medicine and Division of Gastroenterology and Hepatology,
Mayo Clinic Hospital, Phoenix, AZ, said, "Hepatitis C
is the most common chronic blood-borne infection in the developed
world. It afflicts approximately four million people in the
United States alone, about four times the number afflicted
by HIV, the virus that causes AIDS. There is a significant
need to provide hepatitis C patients with additional treatment
options, and Albuferon has looked promising in our initial
studies. Further development in interferon-naive patients
is warranted."
David C. Stump, M.D., Executive Vice President,
Drug Development, said, "Based on the positive interim
clinical results that continue to emerge from our ongoing
Phase 1/2 clinical trial of Albuferon in patients with chronic
hepatitis C, we are pleased to advance Albuferon to a Phase
2 study in patients who are naove to treatments with interferon
alpha.(1)(2) We believe that the Phase 2 study will yield
important additional information about Albuferon's safety,
pharmacology, and biological activity, and also should enable
us to identify an optimal range of doses to evaluate in a
larger 48- week combination study of Albuferon that we plan
to conduct in treatment-naive patients."
Albuferon is a novel, long-acting form
of interferon alpha. Recombinant interferon alpha is approved
for the treatment of hepatitis C, hepatitis B, and a broad
range of cancers. Human Genome Sciences modified interferon
alpha to improve its pharmacological properties by using the
company's proprietary albumin fusion technology. Human Genome
Sciences is developing Albuferon for use in the treatment
of chronic hepatitis C.
Hepatitis C infection is an inflammation
of the liver caused by the hepatitis C virus. The hepatitis
C virus is transmitted primarily through significant or repeated
exposures to infected blood. In the United States, intravenous
drug use and sexual contact with infected persons account
for the majority of new hepatitis C infections. 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 current standard of care for treating chronic
hepatitis C is combination therapy consisting of pegylated
interferon and ribavirin, an antiviral drug.(3)
Health professionals interested in more
information about trials involving HGSI products are encouraged
to inquire via the Contact Us section of the Human Genome
Sciences web site, http://www.hgsi.com/products/request.html,
or by calling (301) 610-5790, extension 3550.
Human Genome Sciences is a company with
the mission to treat and cure disease by bringing new gene-based
protein and antibody drugs to patients.
HGS, Human Genome Sciences and Albuferon
are trademarks of Human Genome Sciences, Inc.
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, 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.
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.
Footnotes:
(1) Balan V, et al. Safety, Pharmacokinetics and Pharmacodynamic
Results of Higher Doses of Albuferon(TM) in a Phase 1/2 Single
and Double Dose-Escalation Study in Treatment Experienced
Subjects with Chronic Hepatitis C. 39th Annual Meeting of
the European Association for the Study of the Liver, Berlin.
April 15, 2004.
(2) Balan V, et al. A Phase 1/2 Study
to Evaluate the Pharmacokinetics, Safety, Tolerability, Immunogenicity,
and Pharmacodynamics of Albuferon(TM)-alpha in Treatment Experienced
Subjects with Chronic Hepatitis C. 54th Annual Meeting of the American Association
for the Study of Liver Diseases, Boston. October 25, 2003.
(3) Strader DB, Wright T, Thomas DL, and
Seeff, LB. AASLD Practice Guideline: Diagnosis, Management,
and Treatment of Hepatitis C. Hepatology 2004 April; 39 (4):
1147-1171.
SOURCE Human Genome Sciences, Inc.
CONTACT: David C. Stump, M.D., Executive Vice President,
Drug Development, +1-240-314-4400, Jerry Parrott, Vice President,
Corporate Communications, +1-301-315-2777, or Kate de Santis,
Director, Investor Relations, +1-301-251-6003, all of Human
Genome Sciences, Inc./
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May 28, 2004
Characteristics
and Survival in Hepatocellular Carcinoma
Source: www.gastrohep.com
The characteristics of patients with hepatocellular
carcinoma have changed dramatically between 1976 and 1995,
find doctors in the latest issue of Cancer.
In this study, doctors from Japan analyzed
changes in the characteristics and survival rate of patients
with hepatocellular carcinoma in the past 25 years.
The team retrospectively evaluated data
from 1365 patients with hepatocellular carcinoma who were
diagnosed, treated, and followed between 1976 and 2000.
They recorded trends in clinical characteristics
and survival rate.
The doctors found that, between 1976 and
1995, the number of patients with smaller tumors, a less advanced
tumor stage, and with a lower Child-Pugh class increased.
There were no differences were observed
in the distributions of these factors between the periods
1991 and 1995, and 1996 and 2000.
Year of diagnosis contributed independently
to improved survival rates.
Cancer
In addition, year of diagnosis, tumor size,
tumor stage, Child-Pugh class, and type of initial treatment
correlated significantly with patient survival rates.
The year of hepatocellular carcinoma diagnosis
was found to contribute to the improvement in patient survival
rates.
Dr Hidenori Toyoda and colleagues concluded,
"The characteristics of patients with hepatocellular
carcinoma changed dramatically from 1976 to 1995 toward the
earlier detection of hepatocellular carcinoma".
"This contributed to the improvement
noted in patient survival rates during this period".
"The year of hepatocellular carcinoma
diagnosis was found to be an independent factor for the improved
survival rates by multivariate analysis".
"This indicated that the progress
of treatment and care for patients with hepatocellular carcinoma
contributed to the annual improvement in patient survival
rates".
Cancer 2004; 100(11): 2415-21
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