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Alan Franciscus
Editor-in-Chief
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In This Issue:
Age at Infection, Degree
of Inflammation Play Role in Rate of Progression of Hepatitis
C
Report Identifies Transplant Trends; Published
in CD-ROM Format for First Time
Hepatocellular Carcinoma in Anti-HCV Positive
Cirrhotic Patients
Hepatitis Drug Researched Here as Anthrax Treatment
Schering-Plough Announces Availability of Peg-Intron
Redipen, Providing The Proven Efficacy of Peg-Intron in an
Easy-to-Use Pen
Mild Hepatitis C Infection Will Rapidly Worsen
in 1 in 3 People Affected
NP/PA Clinical Hepatology Fellowship- Application
Deadline March 15, 2004
SciClone Pharmaceuticals (SCLN) Reports Data:
41% Of Hepatitis C Non-Responder Patients Test HCV RNA Negative
After 24 Weeks Of ZADAXIN Triple Therapy
Anadys Pharmaceuticals Announces Initiation Of
Clinical Trial Of ANA971, An Orally Administered Prodrug Of
Isatoribine
Complementary and Alternative Therapies for
Chronic Hepatitis C
February 16th, 2004
Age
at Infection, Degree of Inflammation Play Role in Rate of
Progression of Hepatitis C
Source:Gut
Harvey McConnell
A large scale British study finds that
among patients with mild hepatitis C (HCV), the infection
will rapidly worsen among 33%, particularly among those who
are older when first infected and those who already have a
degree of inflammation and fibrosis in the liver at diagnosis.
Dr Stephen Ryder, Queen's Medical Centre,
University Hospital, Nottingham, and colleagues in The Trent
HCV Study Group carried out a prospective repeat liver biopsy
study among 214 patients HCV (126 men and 88 women) and their
rate of progression of fibrosis without intervening treatment.
The cohort had a mean age of 36, and their
disease was predominantly mild. Overall, 52% of the patients
admitted to injection drug use and 23% received blood components
prior to 1991 when screening for HCV was introduced in Britain.
There was a median interval of 2.5 years
between biopsies. At first biopsy, the average Ishak (fibrosis)
score was 3, with most patients having scores of 6 or less,
considered to denote mild disease. However, within 30 months,
clinicians found the Ishak score increased by 1 or more points
in 33% of patients, and by 2 or more points in 10%.
Independent predictors of progression were
age at first biopsy and the presence of any fibrosis on first
biopsy. Factors not associated with progression included necroinflammation,
duration of infection, alcohol consumption, alanine aminotransferase
levels, current or past hepatitis B virus infection, ferritin,
HCV genotype, and steatosis or iron deposition in the initial
biopsy.
These findings suggest that hepatitis C
infection may somehow become more fibrogenic with advancing
host age, the clinicians note. This may be one explanation
for the apparent lack of fibrotic liver disease progression
in young women who are infected with hepatitis C via immunoglobulin
anti-D.14.
"Our study avoided the pitfall of
estimated duration of infection by prospectively following
a relatively large group of patients selected to have mild
or moderate liver disease," the clinicians say.
They conclude "that histologically
mild hepatitis C is a progressive disease. The overall rate
of fibrosis progression is low but increased in patients who
are older or have fibrosis on their index biopsy. These data
suggest that HCV infection will place an increasing burden
on health care services in the next 20 years as the population
infected with HCV ages."
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Report Identifies
Transplant Trends; Published in CD-ROM Format for First Time
Source: UNOS News Bureau
newsroom@unos.org
Richmond, Va. -- A newly released report
documents key data and trends regarding organ donation and
transplantation in the United States. For the first time the
PTN/SRTR Annual Report, published since 1990, will be published
exclusively in CD format in addition to being accessible on
the World-Wide Web.
Early Effects of Revised Liver
Policy
This is the first report to include a chapter of data about
a significant change to liver policy adopted in February 2002.
The policy assesses the medical urgency of most liver transplant
candidates based on two formulas, one for adults known as
the Model for End-Stage Liver Disease (MELD) and one for children
known as the Pediatric End-Stage Liver Disease model (PELD).
While the report can only address early effects of the policy,
it notes that higher MELD scores (and thus more priority for
a transplant) are associated with a higher risk of death awaiting
a transplant, suggesting that the system is accurately prioritizing
transplant candidates. The report also notes a decrease in
liver transplant wait list registrations in 2002, which may
be due in part to the new policy's de-emphasis on waiting
time as a factor in liver allocation.
Waiting List Continues to Grow
The increasing need for more donor organs appears as a common
theme in many chapters in this report, more so for pancreas,
liver and kidney transplants. The organ transplant waiting
list saw an increase in the decade of 150 percent in patients
added from 31,694 in 1993 to 79,387 at the end of 2002. Long
wait times for transplant candidates and/or the continued
growth in the waiting list size underscores the continued
problem of the supply of organs not meeting the demand.
Living Donation More Common
Over the decade from 1993 to 2002, living donation has become
much more common, with living donor kidney transplants increasing
from 28 percent of the total kidney transplants performed
in 1993 to 43 percent in 2002. The success of kidney transplantation
prior to starting dialysis on patients with end-stage renal
disease is well recognized and is being touted favorably,
especially by living donor kidney recipients. Kidney transplantation
continues to be recognized as the treatment of choice for
medically suitable patients with end-stage renal disease,
increasing the waiting list for a kidney transplant. The number
of patients waiting for a kidney transplant continues to rise,
from 47,830 in 2001 to 50,855 in 2002, well exceeding the
number of donated kidneys.
Electronic Version Now Available
Over the past few years, the report was published in both
print and electronic forms. With an increasing number of report
users relying primarily on the electronic version, accessed
via the Internet, the 2003 annual report eliminates paper
copy and is being distributed in a new CD-ROM version. Advantages
of the electronic version are clear: greater ease of navigation,
portability, saving resources and rapid table or figure extraction
for individual use.
The 13th Annual Report was produced by
the Scientific Registry of Transplant Recipients (SRTR) contractor,
University Renal Research and Education Association (URREA),
in collaboration with the Organ Procurement and Transplantation
Network (OPTN) contractor, United Network for Organ Sharing
(UNOS), under contract with the Health Resources and Services
Administration (HRSA) of the Department of Health and Human
Services (HHS).
CDs may be ordered by calling 804-782-4841.
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Hepatocellular
Carcinoma in Anti-HCV Positive Cirrhotic Patients
Source: www.gastrohep.com
Doctors, in the latest issue of the Journal
of Internal Medicine, compare prognostic systems in anti-HCV
positive cirrhotic patients with hepatocellular carcinoma.
In this study, doctors from Italy investigated
the usefulness of newly proposed hepatocellular carcinoma
(HCC) prognostic systems in anti-HCV positive cirrhotic patients
with HCC:
• The Cancer of the Liver Italian Program (CLIP) score
• The Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire
(GRETCH) model
• The Barcelona Clinic Liver Cancer (BCLC) staging classification
The team compared these with the known
Okuda staging system. All staging systems were able to identify
the various patient subgroups. Journal of Internal Medicine
The doctors retrospectively applied the
Okuda stage, CLIP score, GRETCH model and BCLC stages in 81
anti-HCV positive cirrhotic patients with HCC.
They compared the ability of these methods
to assess survival prognosis.
Overall, 51 patients died and median survival
was 18 months.
The team found that all staging systems
were able to identify the various patient subgroups with differing
survival.
They determined that the CLIP score, the
GRETCH model and the BCLC staging classification were better
at characterizing 1-year prognosis, compared to the Okuda
staging system.
Dr Giannini's team concluded, "The
prognostic value and usefulness of the CLIP score, the GRETCH
model and the BCLC staging classification was reproduced in
a single-centre analysis of anti-HCV positive HCC cirrhotic
patients".
"These scores provided a prognostic
assessment of our patients which is superior to what was obtained
by the Okuda staging system".
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Hepatitis
Drug Researched Here as Anthrax Treatment
JIM RITTER Health Reporter
Chicago Sun Times
University of Chicago biochemist Wei-Jen
Tang was researching antidotes to anthrax poisoning when out
of the blue he received a call from a researcher working for
a drug company.
The researcher had read about Tang's work
and suggested Tang try his company's hepatitis drug, Hepsera.
Tang was skeptical, but the researcher's
hunch turned out to be a good one. In test tubes, Hepsera
blocks the action of a deadly poison produced by anthrax bacteria.
"This is a classic example of serendipity
in science," said Paula Flicker of the National Institute
of General Medical Sciences, which is helping fund Tang's
work. The study by Tang and colleagues is published in the
online edition of the Proceedings of the National Academy
of Sciences.
Anthrax is one of the most feared weapons
of biological terrorism. In 2001, someone sent anthrax letters
to politicians and journalists, and several people died. In
1993, Congress' Office of Technology Assessment said that
spraying 221 pounds of anthrax above Washington could kill
between 130,000 and 3 million people. However, such an attack
would require access to advanced biotechnology.
Anthrax infection resembles a cold at first,
then progresses to severe breathing problems and shock, and
often is fatal. There are three weapons against anthrax: vaccines,
including new ones under development; antibiotics, which work
only if taken early in the disease, and antidotes against
the poisons produced by anthrax bacteria.
Hepsera is one of several antidotes under
study. The drug, approved for chronic hepatitis B, blocks
the effects of edema factor, an anthrax poison that causes
massive tissue damage.
In 2002, Tang and colleagues published a paper on the toxin.
After reading the paper, Craig Gibbs, a researcher for Hepsera
maker Gilead Sciences, contacted Tang. Gibbs told Tang about
Hepsera and later sent him samples.
Hepsera might block similar toxins produced
by bacteria that cause whooping cough, plague and hospital
infections, Tang said. Hepsera's side effects include weakness,
headache, stomach pain and nausea.
Tang is testing Hepsera on mice infected
with anthrax, and if he gets funding, would like to do tests
on rabbits and monkeys.
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February 17th, 2004
Schering-Plough
Announces Availability of Peg-Intron Redipen, Providing The
Proven Efficacy of Peg-Intron in an Easy-to-Use Pen
FIRST AND ONLY PRECISION DOSING PEN FOR ADMINISTERING PEGINTERFERON
THERAPY FOR CHRONIC HEPATITIS C
Source: Company Press Release
Schering-Plough Corporation (NYSE: SGP)
today announced the U.S. launch of PEG-INTRON REDIPEN™,
which provides the proven efficacy of PEG-INTRON® (peginterferon
alfa-2b) Powder for Injection in an easy-to-use pen. The PEG-INTRON
REDIPEN is the first and only pen delivery system approved
for administering pegylated interferon therapy for chronic
hepatitis C, a potentially lethal virus that has overtaken
HIV as the most common blood-borne infectious disease in the
United States. An estimated 2.7 million Americans are chronically
infected with hepatitis C.
PEG-INTRON REDIPEN is designed to be patient-friendly
with features such as an easy-to-read dial-up dosing button
for precise, individualized weight-based dosing of PEG-INTRON,
a self-priming action that automatically removes air bubbles
from the pen prior to patient self-administration and a small
needle size (30-gauge) to minimize patient discomfort.
“For successful treatment of patients
with hepatitis C, it is important that they take their medicine
consistently and get the appropriate dose for their individualized
therapy,” said Bruce R. Bacon, M.D., professor of internal
medicine, director, division of gastroenterology and hepatology,
Saint Louis University School of Medicine. “With the
small needle, self-priming feature and large, easy-to-read
dosing knob, PEG-INTRON REDIPEN is designed to help patients
feel confident that they are getting an accurate dose and
offers an easy-to-use alternative for people who may be intimidated
by a traditional needle and syringe system.”
PEG-INTRON used in combination with REBETOL®
(ribavirin, USP) has proven effective in treating patients
with chronic HCV infection, including American patients infected
with genotype 1 virus, the most common and difficult to treat
form of the disease.
The PEG-INTRON REDIPEN is a disposable,
one-time use precision dosing system that allows patients
to administer PEG-INTRON in three easy steps: Mix, Dial and
Deliver. Mixing occurs by simply pushing down on the pen to
combine the PEG-INTRON powder with sterile water, both of
which are stored in the body of the pen; Dialing allows patients
to accurately select their predetermined individualized dose;
and Delivery allows patients to inject their individualized
dose of the medication. The PEG-INTRON REDIPEN is available
in four different strengths (50, 80, 120 and 150 mcg), each
indicated by a color-coded label and dosing button. An instructional
videotape and brochure are available for use by patients and
healthcare professionals.
“Schering-Plough is committed to
providing innovative products and patient services to people
with chronic hepatitis C,” said Robert J. Spiegel, M.D.,
senior vice president of medical affairs and chief medical
officer, Schering-Plough Research Institute. “We are
pleased to introduce PEG-INTRON REDIPEN to further help meet
the needs of the hepatitis C patient community,” he
said.
Since the introduction of PEG-INTRON and
REBETOL combination therapy in 2001, more than 300,000 hepatitis
C patients worldwide have received this treatment, including
more than 200,000 U.S. patients.
Commitment to Hepatitis C Patients
As the leading innovator of interferon-based treatments for
hepatitis C, Schering-Plough on Sept. 23, 2003, announced
plans to initiate the IDEAL trial (Individualized Dosing Efficacy
vs. flat dosing to Assess optimaL pegylated interferon therapy),
a major clinical study involving 2,880 patients that for the
first time will directly compare the two approved forms of
pegylated interferon therapy for chronic hepatitis C: PEG-INTRON
versus PEGASYS (peginterferon alfa-2a/Hoffmann-La Roche, Inc.),
both used in combination with ribavirin. Schering-Plough Research
Institute, in collaboration with leading medical centers,
will conduct the comparative study in response to requests
by the hepatitis C medical and patient communities, and to
clear up misperceptions in the marketplace about these two
treatments.
In addition to its ongoing commitment to
research and development, Schering-Plough is committed to
supporting hepatitis C patients with education and service
programs as well as to help locate financial assistance for
patients in need. The company’s programs for patients
in the United States are among the most comprehensive in the
industry, providing support and guidance to patients, and
ensuring that all eligible patients have access to the company’s
hepatitis C products.
Schering-Plough’s Be In Charge hepatitis
C patient-support program has enrolled approximately 95,000
U.S. patients since its inception in 1997. This U.S. program
is designed to support patients treated with Schering-Plough
hepatitis C products through the use of educational materials
and telephone contact with personal nurse counselors skilled
in the management of hepatitis C.
The company’s Commitment to Care
program is designed to ensure that eligible U.S. patients
have access to Schering-Plough’s hepatitis products,
either by assisting patients in obtaining the reimbursement
or assistance for which they qualify, or by providing products
free of charge to eligible patients. The market value of treatment
provided to hepatitis C patients through this program exceeded
$150 million in 2003.
PEG-INTRON and REBETOL combination therapy
is indicated for the treatment of chronic hepatitis C in patients
with compensated liver disease who have not been previously
treated with interferon alpha and are at least 18 years of
age.
PEG-INTRON is a longer-acting form of INTRON® A (interferon
alfa-2b, recombinant) Injection that uses proprietary PEG
technology developed by Enzon, Inc. (NASDAQ: ENZN) of Bridgewater,
N.J.
PEG-INTRON, recombinant interferon alfa-2b
linked to a 12,000 dalton polyethylene glycol (PEG) molecule,
is a once-weekly therapy that is designed to achieve an effective
balance between antiviral activity and elimination half-life.
Schering-Plough holds an exclusive worldwide license to PEG-INTRON.
INTRON A is a recombinant version of naturally
occurring alpha interferon, which has been shown to exert
both antiviral and immunomodulatory effects. Schering-Plough
markets INTRON A for 16 major antiviral and anticancer indications
worldwide.
REBETOL is an oral formulation of ribavirin,
a synthetic nucleoside analog. Schering-Plough has worldwide
rights to market oral ribavirin for hepatitis C through a
licensing agreement with Valeant Pharmaceuticals International
(NYSE: VRX), formally ICN Pharmaceuticals, of Costa Mesa,
Calif.
WARNING
REBETOL monotherapy is not effective for the treatment of
chronic hepatitis C virus infection and should not be used
alone for this indication. (See WARNINGS.)
•The primary toxicity of ribavirin is hemolytic anemia.
The anemia associated with REBETOL therapy may result in worsening
of cardiac disease that has led to fatal and nonfatal myocardial
infarctions. Patients with a history of significant or unstable
cardiac disease should not be treated with REBETOL. (See WARNINGS,
ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION.)
•Significant teratogenic and/or embryocidal effects
have been demonstrated in all animal species exposed to ribavirin.
In addition, ribavirin has a multiple-dose half-life of 12
days, and so it may persist in nonplasma compartments for
as long as 6 months. Therefore, REBETOL therapy is contraindicated
in women who are pregnant and in the male partners of women
who are pregnant. Extreme care must be taken to avoid pregnancy
during therapy and for 6 months after completion of treatment
in both female patients and in female partners of male patients
who are taking REBETOL therapy. At least two reliable forms
of effective contraception must be utilized during treatment
and during the 6-month post-treatment follow-up period. (See
CONTRAINDICATIONS, WARNINGS, PRECAUTIONS-Information for Patients
and Pregnancy Category X.)
•Alpha interferons, including PEG-INTRON and INTRON
A, may cause or aggravate fatal or life-threatening neuropsychiatric,
autoimmune, ischemic and infectious disorders. Patients should
be monitored closely with periodic clinical and laboratory
evaluations. Patients with persistently severe or worsening
signs or symptoms of these conditions should be withdrawn
from therapy. In many but not all cases these disorders resolve
after stopping therapy with PEG-INTRON or INTRON A. (See WARNINGS,
ADVERSE REACTIONS.)
PEG-INTRON
There are no new adverse events specific to PEG-INTRON as
compared to INTRON A, however, the incidence of some (e.g.,
injection site reactions, fever, rigors, nausea) were higher.
The most common adverse events associated with PEG-INTRON
were “flu-like” symptoms, occurring in approximately
50% of patients, which may decrease in severity as treatment
continues. Application site disorders were common (47%), but
all were mild (44%) or moderate (4%) and no patient discontinued,
and included injection site inflammation and reaction (i.e.,
bruise, itchiness, irritation). Injection site pain was reported
in 2% of patients receiving PEG-INTRON. Alopecia (thinning
of the hair) is also often associated with alpha interferons
including PEG-INTRON.
Psychiatric adverse events, which include
insomnia, were common (57%) with PEG-INTRON, but similar to
INTRON A (58%). Depression was most common at 29%. Suicidal
behavior including ideation, suicidal attempts, and completed
suicides occurred in 1% of patients during or shortly after
completing treatment with PEG-INTRON. PEG-INTRON is contraindicated
in patients with autoimmune hepatitis and decompensated liver
disease.
The following serious or clinically significant
adverse events have been reported at a frequency <1% with
PEG-INTRON or interferon alpha: Severe decreases in neutrophil
or platelet counts, hypothyroidism, hyperglycemia, hypotension,
arrhythmia, ulcerative and hemorrhagic colitis, development
or exacerbation of autoimmune disorders including thyroiditis,
RA, systemic lupus erythematosus, psoriasis, pulmonary disorders
(dyspnea, pulmonary infiltrates, pneumonitis and pneumonia,
some resulting in patient deaths), urticaria, angioedema,
bronchoconstriction, anaphylaxis, retinal hemorrhages and
cotton wool spots.
Renal failure patients should be closely
monitored for signs and symptoms of interferon toxicity and
PEG-INTRON should be used with caution in patients with creatinine
clearance <50 mL/min. Patients on PEG-INTRON therapy should
have hematology and blood chemistry testing before the start
of treatment and then periodically thereafter.
INTRON A
All patients receiving INTRON A therapy experienced mild-to-moderate
side effects. Some patients experienced more severe side effects,
including neutropenia, fatigue, myalgia, headache, fever,
chills and increased SGOT. Other frequently occurring side
effects were nausea, vomiting, depression, alopecia, diarrhea
and thrombocytopenia. DEPRESSION AND SUICIDAL BEHAVIOR, INCLUDING
SUICIDAL IDEATION, SUICIDAL ATTEMPTS, AND COMPLETED SUICIDES,
HAVE BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALFA
INTERFERONS, INCLUDING INTRON A THERAPY.
DISCLOSURE NOTICE: The information
in this press release includes certain “forward-looking”
statements concerning PEG-INTRON REDIPEN in the United States,
the market for drugs to treat hepatitis C and Schering-Plough’s
products. Forward-looking statements are subject to risks
and uncertainties, which may cause actual results to differ
materially. These risks and uncertainties include product
availability, current and future branded, generic and OTC
competition, market acceptance of new products, timing of
trade buying, and patent positions. For further details and
a discussion of these and other risks and uncertainties, see
the company’s Securities and Exchange Commission filings,
including the third quarter 2003 Form 10-Q.
Schering-Plough is a research-based company
engaged in the discovery, development, manufacturing and marketing
of pharmaceutical products worldwide.
For more information about Schering-Plough,
visit the company’s website at www.schering-plough.com.
For information about hepatitis and for full prescribing information
regarding PEG-INTRON and REBETOL, visit www.hepatitisinnovations.com.
PEGASYS is a trademark of Hoffmann-La Roche
Inc. See the PEGASYS product insert for information on this
product.
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Mild Hepatitis
C Infection Will Rapidly Worsen in 1 in 3 People Affected
Newswise -- Mild hepatitis C infection will rapidly worsen
in one in three of those affected, suggests new research published
in the medical journal Gut. This is particularly
likely in those who are older when first infected, and those
who already have a degree of inflammation and fibrosis in
their liver at diagnosis.
The viral liver infection hepatitis C (HCV)
is mainly passed on through injecting drug use and blood transfusions
before 1991, when the screening of blood products for the
virus was introduced. HCV is an important cause of chronic
liver disease, eventually leading to liver cancer. But treatment
with interferon is complicated and expensive, and only works
in around one in two of those treated.
The authors base their conclusions on 214
patients with HCV whose average age was 36; 126 of them were
men and their liver disease was mostly mild. None of the patients
was given any treatment, and they were monitored by tissue
sampling of their liver every 2.5 years.
One in two of the patients admitted to
having used intravenous drugs in the past; almost one in four
had been transfused with infected blood products.
At the first biopsy, the average fibrosis
score (Ishak score) was 3. Most patients had scores of 6 or
less; scores of up to 6 are considered to denote mild disease.
Within 30 months, when the next tissue sample was taken, the
Ishak score had increased by one or more points in a third
(70) of the patients, and by two or more points in one in
10 of them.
The factors influencing progression of
the disease were older age at infection, rather than the length
of infection, and degree of inflammation and scarring at the
first biopsy.
Unlike the results of previous research,
gender, alcohol consumption, virus type and other indicators
of poor liver function did not seem to have any effect on
the rate of progression, although the authors point out that
it is important to reduce alcohol consumption once infected.
The authors conclude that even mild HCV
is a progressive disease, and those patients affected are
likely to require a considerable degree of health care as
they age over the next 20 years.
To read the entire paper, go to: http://press.psprings.co.uk/gut/
march/451_gt21691.pdf
Source: British Medical Journal
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February 18th, 2004
NP/PA Clinical
Hepatology Fellowship - Application Deadline March 15, 2004
Source: AASLD E-News
AASLD has established a Clinical Hepatology
Fellowship Program for NP's/PA's which provides one-year salary
and benefit support for certified and licensed physician assistants
or nurse practitioners and is designed to:
• Increase the number of trained
nurses/mid-level practitioners in clinical hepatology.
• Facilitate the transition (or shift in emphasis) into
clinical hepatology for nurses/mid-level practitioners.
• Increase access for liver disease patients to adequately
trained clinicians.
In order to be eligible for this award,
the applicant must meet the following criteria:
• The applicant's training will be
sponsored by a Clinical Hepatologist, practicing in an environment
conducive to training in hepatology.
• The mentor must be a member of
AASLD and must dedicate at least 50% of his/her time to the
care of patients with liver diseases.
• The applicant must be a citizen
or permanent resident of the U.S.
• The majority of the applicant's
time (greater than 80%) will be focused on clinical care in
hepatology.
• The applicant will not hold other,
similar research awards during the fellowship period (July
1, 2004 - June 30, 2005).
Contact Lee Claassen (lclaassen@aasld.org)
or Denise Davis (ddavis@aasld.org)
at 703-299-9766.
Support of this award by Roche Laboratories Inc. and Schering
Hepatitis Innovations is gratefully acknowledged.
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SciClone
Pharmaceuticals (SCLN) Reports Data: 41% Of Hepatitis C Non-Responder
Patients Test HCV RNA Negative After 24 Weeks Of ZADAXIN Triple
Therapy
Pilot Trial Treating Patients Not Responding to Prior
Therapy Continues to Show Positive Results SciClone Pharmaceuticals,
Inc.
SAN MATEO, Calif.--SciClone Pharmaceuticals,
Inc. today reported positive data from a pilot clinical trial
in hepatitis C patients who have not responded to previous
therapy. 41% of the non-responder patients tested HCV RNA
negative and 50% showed a virologic response after 24 weeks
of a new triple therapy of ZADAXIN® in combination with
pegylated interferon alpha and ribavirin. By comparison, separate
recent studies show that after 24 weeks of double therapy
with pegylated interferon alpha plus ribavirin, approximately
30% of hepatitis C non-responder patients tested HCV RNA negative.
Dr. Eduardo Martins, Vice President of
Medical Affairs of SciClone Pharmaceuticals, commented, "As
we continue to explore ways to further improve therapy options
for the nearly half of hepatitis C patients that do not respond
to the current standard of care, we are pleased to see ZADAXIN
used in combination with standard dose pegylated interferon
and low dose ribavirin has improved response rates in this
patient group without adding toxicity. Building on these positive
interim data, we are closely monitoring the progress of this
trial and are considering future triple therapy studies. Our
primary focus remains our two ongoing U.S. phase 3 clinical
trials targeting ZADAXIN in combination with pegylated interferon
alpha to be the first FDA approved therapy to specifically
address the needs of non-responders."
About the Triple Therapy Trial
This ongoing open label clinical trial plans to enroll a total
of 50 hepatitis C non-responder patients, none of which have
responded to prior therapy of at least six months of interferon
alpha in combination with ribavirin. During the course of
this study, patients will receive 12 months of triple therapy
and will be observed for six months after completing therapy
to measure sustained response, defined as negative HCV RNA
by PCR test measured at week 72.
Of the 22 patients who had completed 24
weeks of triple therapy of ZADAXIN in combination with pegylated
interferon alpha and ribavirin, 41% (9/22) tested negative
for HCV RNA by PCR test and 50% (11/22) showed a virologic
response to therapy, defined as a 2 log or greater reduction
in the level of HCV RNA. Of the 19 patients infected with
the difficult to treat HCV genotype 1, 42% (8/19) tested negative
for HCV RNA and 58% (11/19) showed a virologic response to
therapy. As in all previous ZADAXIN studies, the safety profile
was excellent without significant ZADAXIN related side effects
or toxicities.
In October 2003, SciClone reported 12 week
interim data from this trial. After 12 weeks of triple therapy,
61% (14/23) of hepatitis C non-responder patients reported
an early virologic response, or EVR, defined as a 2 log or
greater reduction in the level of HCV RNA, and 48% (11/23)
tested negative for HCV RNA. Of the 20 patients infected with
the difficult to treat HCV genotype 1, 60% (12/20) reported
an EVR and 50% (10/20) tested negative for HCV RNA.
During the course of this pilot clinical
trial, patients will receive 12 months of triple therapy of
a standard dose of ZADAXIN (1.6 mg/bi-weekly) plus a standard
dose of pegylated interferon alfa-2a (180 mcg/week) and a
low dose of ribavirin (800-1,000 mg/day) and will be observed
for six months after completing therapy to measure sustained
response. The primary endpoint of the study is negative HCV
RNA by PCR test measured at weeks 48 and 72. The secondary
endpoints are normalization of ALT (a liver enzyme) measured
at weeks 48 and 72 and reduction in HCV load measured at weeks
12, 24, 48, and 72.
This multicenter study is being conducted
by a team lead by Dr. Jorge L. Poo, Chief Scientific Officer
of CIF-Biotech at the Medica Sur hospital in Mexico City (www.cifbiotec.org.mx).
The triple therapy study is being funded and conducted by
Laboratorios Colombia in Mexico with ZADAXIN provided free
of charge by SciClone and PEGASYS® brand pegylated interferon
alpha provided free of charge by F. Hoffman La-Roche. ZADAXIN,
PEGASYS and ribavirin are approved in Mexico for the treatment
of hepatitis C.
About ZADAXIN
ZADAXIN is a pure synthetic preparation of thymosin alpha
1, a substance which circulates in the blood naturally and
is instrumental in the body's immune response to fight viral
infections and certain cancers. ZADAXIN is easily and safely
administered just under the skin twice a week. After administration,
thymosin alpha 1 circulates at 50 to 100 times its normal
level in the body. ZADAXIN has been approved for sale by the
ministries of health in over 30 countries and is marketed
in China and selected other countries outside the U.S. SciClone
estimates that over 10,000 patients have used ZADAXIN in both
clinical and commercial use, alone and in combination with
anti-viral and anticancer drugs, without any reported significant
ZADAXIN-specific side effects or toxicities.
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 late stage clinical trials, including two
phase 3 hepatitis C clinical trials in the U.S., a recently
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., and a hepatitis C
pilot clinical trial in Mexico. Other drug development candidates
include SCV-07, a potentially orally available therapeutic
to treat viral and infectious diseases, and other products
to treat cystic fibrosis. For more information about SciClone,
visit www.sciclone.com.
The information in this press release contains
forward-looking statements including the prospective development,
commercialization and regulatory approval of ZADAXIN in the
U.S. Words such as "expects," "plans,"
"believe," "may," "will," "anticipated,"
"intended" and variations of these words or similar
expressions are intended to identify forward-looking statements.
In addition, any statements that refer to expectations, projections
or other characterizations of future events or circumstances,
including any underlying assumptions, are forward-looking
statements. These statements are not guarantees of future
performance and are subject to risks, uncertainties and assumptions
that are difficult to predict. Therefore, our actual results
could differ materially and adversely from those expressed
in any forward-looking statements as a result of various factors,
including the fact that results from studies with a limited
group of patients may not be predictive of the results of
larger studies, 24-week results are not always predictive
of the achievement of a sustained viral response which is
the endpoint of the hepatitis C clinical trial, the speed
with which patients are enrolled in the hepatitis C clinical
trial, maintenance of the sufficiency and eligibility of the
enrolled patient population, unexpected adverse results to
patients and other events that could prolong the clinical
trial or result in unanticipated expense, we may not receive
hepatitis C approval for ZADAXIN in the U.S., future actions
that may be taken by regulatory agencies, as well as other
risks and uncertainties described in SciClone's filings with
the Securities and Exchange Commission.
Contact:
SciClone Pharmaceuticals, Inc. Richard A. Waldron, 650-358-3437
Source: SciClone Pharmaceuticals, Inc.
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February 19th, 2004
Anadys Pharmaceuticals
Announces Initiation Of Clinical Trial Of ANA971, An Orally
Administered Prodrug Of Isatoribine
Anadys Pharmaceuticals initiates Phase I clinical trial
of isatoribine prodrug for study as a hepatitis C therapy
SAN DIEGO--(BUSINESS WIRE)--Anadys Pharmaceuticals,
Inc. ("Anadys") announced today that it has initiated
a clinical trial of ANA971, an orally administered prodrug
of isatoribine. Isatoribine is a nucleoside analog in development
for the treatment of chronic hepatitis C virus (HCV) infection.
To date, isatoribine has been administered to 48 subjects,
including 28 patients chronically infected with HCV. A recent
clinical study showed that intravenous administration of isatoribine
was well tolerated and safe at all doses tested. Interim results
from that study have also shown preliminary biological activity
and viral load reduction in the patient populations whose
clinical data has been completed and analyzed. ANA971, which
was discovered by Anadys, is a prodrug designed to improve
the oral bioavailability of isatoribine. Anadys has exclusive
rights to market and commercialize isatoribine and ANA971
worldwide.
In preclinical animal studies, oral administration
of ANA971 resulted in higher levels of isatoribine in the
blood than were present after oral administration of isatoribine
itself. The objectives of this clinical trial are to assess
safety and pharmacokinetics in healthy volunteers following
oral administration of ANA971.
"Initiation of this clinical trial
represents another important step toward our goal of improvement
of HCV patient care, and builds on the results of clinical
work we have conducted with isatoribine," said Devron
Averett, Ph.D., Senior Vice President of Drug Development
for Anadys.
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 TLR7, 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(a). Anadys is currently
enrolling patients for an isatoribine Phase I/II study.
About hepatitis C
HCV causes inflammation of the liver and degradation of liver
function. HCV infection is currently the most common chronic
blood-borne infection in the United States. Approximately
2.7 million people in the United States are chronically infected
with HCV, and it causes 10,000 to 12,000 deaths a year in
the United States. The Centers for Disease Control and Prevention,
or CDC, estimates the annual mortality rate in the United
States could increase to 38,000 by the year 2010, surpassing
the number of deaths attributed annually to HIV/AIDS. HCV
is transmitted primarily through significant or repeated exposures
to infected blood. Approximately two thirds of new infections
progress to chronic infection. Chronic HCV infection may also
progress to more serious complications such as cirrhosis of
the liver, liver cancer, and death.
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
and powerful small molecule, anti-infective medicines for
the treatment of chronic viral hepatitis, including HCV and
HBV, and bacterial infections. Anadys integrates biology and
chemistry into a seamless, feedback-based, iterative process
to facilitate rapid and successful drug discovery. The approach
is designed to advance a strong and continual pipeline of
drug candidates into the clinic and ultimately the market.
For more information, please visit
www.anadyspharma.com
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, the trend toward viral load reduction
resulting from administration of isatoribine in those patients,
the believed mechanism of action of isatoribine and its effect
on a patient's immune system, and expectations regarding further
clinical trials of isatoribine and ANA971. 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 may not be predictive of future results, and Anadys
can provide no assurances that ANA971 will have favorable
results in clinical trials, that isatoribine will have favorable
results in later clinical trials, or that either isatoribine
or ANA971 will receive regulatory approval. This and other
factors that may cause actual results to differ are more fully
discussed in the "Risk Factors" section of Anadys'
Registration Statement on Form S-1 on file with the SEC. 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.
(a) Note to editors: In the value -0.94 log10 units, the 10
in log10 should be subscript.
Contact: Anadys Pharmaceuticals, Inc. Vice-President, Corporate
Development and Strategy Michael Kamdar, 858-530-3667 cc@anadyspharma.com
or Atkins & Associates Sr. Vice President Carin Canale,
858-527-3498 ccanale@irpr.com
Source: Anadys Pharmaceuticals,
Inc.
Source: BioSpace
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February 20th, 2004
Complementary
and Alternative Therapies for Chronic Hepatitis C
Source: www.gastrohep.com
Doctors, in the March issue of the Journal
of Hepatology, identify several promising complimentary
therapies for the treatment of chronic hepatitis C.
Complementary therapies are widely used
by patients with hepatitis C.
In this study, doctors from England assessed
the efficacy of complementary therapies in treating chronic
hepatitis C.
The team conducted systematic searches
of 6 databases. The reference lists of all identified papers
were checked for further relevant publications and information
was requested from experts. No language restrictions were
imposed.
The team identified 27 eligible randomized
clinical trials were located involving herbal products and
supplements. No trials were identified for any other complementary
therapy.
In 14 of the trials, patients received
interferon-alpha in combination with the complementary therapy.
The team determined that less than half
the trials were of good methodological quality.
They found that significant improvements
in virological and/or biochemical response were seen in trials
of vitamin E, thymic extract, zinc, traditional Chinese medicine,
Glycyrrhiza glabra and oxymatrine.
Drs Joanna Thompson Coon and Edzard Ernst
concluded, "We identified several promising complementary
therapies, although extrapolation of the results is difficult
due to methodological limitations".
"More research is warranted to establish
the role of these and other therapies in the treatment of
hepatitis C".
J Hepatol 2004; 40(3): 491-500
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