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Alan Franciscus
Editor-in-Chief
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In This Issue:
• NIH
Panel Examines Conflict-of-Interest Deals, Drafts Recommendations
• HCV Superinfection Hazardous in Hepatitis
B Patients
• Organ Donations Stagnant in Canada Despite
Growing Need for Transplants
• Explores New Combination Therapy In Hepatitis
B Clinical Trial
• No 'Safe' Alcohol Intake Found with Hepatitis
C
• Results of Largest Controlled Clinical
Trial in Hepatitis B "e" Antigen-negative Patients;
Resistance Analysis and Post-Seroconversion Data Presented
• PEGASYS and COPEGUS Now Offers Benefits
in a Wider Range of Hepatitis C Patients
• The Tainted-Blood Scandal Lives On
• PEGASYS® More Effective than Lamivudine,
the Drug Most Commonly Used in Difficult-to-Treat Chronic
Hepatitis B
• Vertex Pharmaceuticals (VRTX) Reports
Data On Investigational Hepatitis C Therapies Suggesting Potential
For Novel Treatment Approaches
• Metabasis Therapeutics Reports The Earning
Of A Milestone Payment Based On Continued Development Of Remofovir
For The Treatment Of Hepatitis B
• Valeant Pharmaceuticals Presents Details
of 24-Week Data for Viramidine Phase 2 Clinical Trials
April 12th, 2004
NIH Panel Examines Conflict-of-Interest
Deals, Drafts Recommendations
Candace Hoffmann
Source: First Word
A National Institutes of Health panel looking
into alleged conflicts of interest involving its directors
and scientists has drafted a report of recommendations on
handling consulting deals with biotechnology and pharmaceutical
companies, the Los Angeles Times reports.
The NIH Blue Ribbon Committee on Conflict
of Interest Policies has stopped short of recommending a ban
on such consulting agreements but states in its report that
there should be full public disclosure on such deals and that
employees should not accept stock or stock options from the
industry. The panel "recommends that paid consulting
not exceed 500 hours a year and that 'special scrutiny be
applied' if outside compensation exceeds half of an employee's
yearly salary at NIH," the newspaper reports.
The 10-member committee was appointed by
NIH director Elias A. Zerhouni after a Los Angeles Times article
reported that two directors of NIH institutes received hundreds
of thousands of dollars in company fees or stock options and
that more than 94 percent of "top-paid NIH employees
were not filing public income-disclosure reports." Three
NIH directors contacted by the Times agreed that directors
should not accept compensation from biotechs and drugmakers
in the future, and Zerhouni said that as of January, institute
directors were no longer accepting consulting fees.
Compensation to NIH scientists would be
assessed on a case-by-case basis, he said, and an outright
ban would not be implemented. "[The agreements] are designed
to encourage government scientists to work with private sector
scientists in order to speed the translation of research findings
to the marketplace," Barbara M. McGarey, an NIH lawyer,
is quoted as telling the panel last month. "The result
is that government research doesn't sit around and never get
developed into products."
The panel will submit its final report
to Zerhouni in early May.
Back to top
April 14th, 2004
HCV
Superinfection Hazardous in Hepatitis B Patients
David Douglas
Source: Reuters Health
NEW YORK--- Acute hepatitis C virus (HCV)
superinfection may have serious consequences in patients with
chronic hepatitis B virus (HBV) infection, Taiwanese researchers
report in the April issue of Gastroenterology. The
outcome is ultimately worse than that following hepatitis
delta virus (HDV) superinfection.
In fact, as lead investigator Dr. Yun-Fan
Liaw told Reuters Health, "in view of the grave prognosis,
especially of HCV superinfection, it is very important to
prevent the transmission of these viruses to patients with
underlying liver disease."
Dr. Liaw, and colleagues at Chang Gung
University in Taipei, came to this conclusion following a
study of various groups of HBV patients. These included 93
HBV patients with HCV superinfection and 190 HBV patients
with HDV superinfection.
The acute HCV superinfection typically
occurred as acute icteric hepatitis. Hepatic decompensation
developed in 34% of these patients, hepatic failure was seen
in 11% and 10% died. The corresponding proportions in HDV
superinfection were 31%, 9% and 7%.
However, follow-up showed that in the HCV
group, the 48% cumulative incidence of cirrhosis at 10 years
was significantly higher than that in the HDV superinfection
group or in those with chronic HBV infection alone. This was
also true of hepatocellular carcinoma in the HCV group--the
incidence at 10 years was 14% and reached 32% at 20 years.
Thus, the researchers conclude that the
long-term prognosis of HCV superinfection in such patients
is "much worse than that following acute HDV superinfection
or active chronic hepatitis B."
Gastroenterology 2004;126:1024-1029.
Back to top
Organ
Donations Stagnant in Canada Despite Growing Need for Transplants
Source: Canadian Press
TORONTO (CP) --- Despite continued appeals
for Canadians to sign donor cards and for families who lose
loved ones to give "the gift of life," the rate
of organ donation for transplants has stagnated over the last
decade, new research shows.
The Canadian Institute for Health Information,
releasing its latest figures on organ procurement Wednesday,
said the rate of donations across the country is continuing
to fall far short of the need for transplants.
In 2003, 124 of every million Canadians
- or almost 4,000 people - were waiting for new organs. But
the rate of donations was a fraction of that, at just 13.5
organs per million in population, said the institute, an independent,
not-for-profit organization working to improve the health
of Canadians and the health-care system.
"The flat donor rate in Canada over
the past 10 years is in part due to socio-demographic factors
such as the aging population and fewer traumatic-injury deaths,"
Dr. John Gill, a kidney transplant specialist in Vancouver,
said in a statement Wednesday.
"Canada's aging population not only
contributes to increased demand for organ transplantation,"
but also affects donations, Gill said. "Many older donors
have health conditions that preclude their organs from being
retrieved and used for transplantation."
For the third year running, the number
of living donors - those who donate one of their kidneys or
part of their liver - was greater than the number of deceased
donors: 438 compared with 428, the CIHI said.
Provincially, organ donation from cadavers
was highest in Quebec and Saskatchewan (19 per million population)
and lowest in British Columbia (nine per million) and Manitoba
(10.3 per million). However, living organ donation rates were
highest in Alberta (19.3), Manitoba (18.1) and British Columbia
(17.8). The lowest rates were reported in Quebec (6.9) and
Saskatchewan (9.0).
While the number of Canadians on waiting
lists for organs at the end of 2003 was down slightly over
the previous two years, to 3,914 from 3,956 patients in 2002
and 3,964 in 2001, Gill said he believes the decline doesn't
"reflect a reduction in the need for organs."
"Rather, given the long waits for
a transplant, there is a growing trend among physicians in
Canada to list patients at later stages in their end-stage
organ disease," he said.
At the close of 2003, patients needing
kidney transplants made up 73 per cent of the waiting list.
Overall, 250 Canadians - about five each week - died that
year while waiting for new organs. Among them were 82 waiting
for a kidney, 100 for a liver, 30 needing a heart, 26 a lung
and 12 needing other organs or a combination transplant.
But when organs were available, each deceased
donor helped an average of three patients. Living donors provided
403 kidneys and 35 liver lobes, representing 38 per cent of
all kidney transplants and nine per cent of all liver transplants
in 2003, CIHI said.
The only bright spot on the donation front
was an increased number of lungs available: the number of
lung/heart-lung transplants averaged 127, compared with an
average of 86 during the previous four years. The CIHI attributes
the change to increased retrieval of lungs from deceased donors
in Canada and an increase in imports of lungs from the United
States. (Cross-border organ sharing occurs when there are
no matched recipients within the country of origin.)
Gill noted that next week is National Organ
and Tissue Donor Awareness Week, a good time for Canadians
to make plans for organ donation by signing donor cards and
talking to family members about their wishes.
"One donor can save up to eight lives
through organ donation and save or improve up to 50 lives
through corneal, bone, skin and other tissue transplants,"
he said.
Back to top
Explores
New Combination Therapy In Hepatitis B Clinical Trial
Trial Uses High Dose of ZADAXIN in Combination with Lamivudine
Source: Business Wire
SAN MATEO, Calif.--April 14, 2004--SciClone
Pharmaceuticals (Nasdaq:SCLN - News) today announced an ongoing
randomized placebo-controlled clinical trial in Taiwan using
a high dose of ZADAXIN® in combination with lamivudine,
the most widely used treatment for chronic hepatitis B, to
explore the possibility of increasing the efficacy of current
treatment for chronic hepatitis B patients. This SciClone
sponsored study is designed to build on both the immunomodulator
effects of ZADAXIN and the potent anti-viral capabilities
of nucleoside analog drugs such as lamivudine. SciClone holds
a granted U.S. patent for the treatment of hepatitis B using
ZADAXIN in combination with lamivudine that does not expire
until 2018. The primary objective of this study is to demonstrate
that patients receiving the ZADAXIN lamivudine combination
therapy could achieve a significantly higher sustained response
rate than patients receiving lamivudine monotherapy, while
limiting the use of lamivudine to one year. Lamivudine has
been shown to be very effective in suppressing the hepatitis
B virus. However, long-term use of lamivudine has been shown
to lead to serious HBV mutations. Viral mutations are seen
after one year of lamivudine therapy and the incidence of
mutation continues to increase with time reaching approximately
55% after three years. Associated with these mutations is
the development of viral resistance to lamivudine making therapy
more difficult. In addition, lamivudine's overall efficacy
is limited. Data show that lamivudine therapy produces a sustained
seroconversion (the disappearance of HBV e-antigen and the
detection of the antibody to the HBV e-antigen) in only 16%
of Asian patients. A separate study using the latest approved
HBV therapy, adefovir dipivoxil, a nucleotide analog with
a similar mechanism of action as lamivudine, produced a sustained
seroconversion in only 12% of patients. In comparison to these
studies, ZADAXIN as a monotherapy in a completed phase 3 clinical
trial in Japan has demonstrated a sustained seroconversion
in 19% of patients receiving low dose (0.8 mg, twice weekly)
ZADAXIN and in 22% of patients receiving standard dose (1.6
mg, twice weekly) ZADAXIN. Patients who achieve a sustained
seroconversion are widely considered to be cured of chronic
hepatitis B.
In this new combination study one group
of patients is receiving a high dose of ZADAXIN (3.2 mg, twice
weekly) for six months plus a standard dose of lamivudine
(100 mg, once a day) for 12 months. The other group of patients
is receiving the same dose of lamivudine (100 mg, once a day)
for 12 months plus a placebo. Upon completing the 12 months
of therapy, each patient will be followed for a six month
observation period. Endpoints of the study are the disappearance
of HBV DNA and the achievement of sustained seroconversion.
The study is being led by Dr. Yun-Fan Liaw at Chang Gung Memorial
Hospital in Taiwan, who plans to enroll by the end of 2004
a total of approximately 120 patients suffering from chronic
hepatitis B.
Dr. Yun-Fan Liaw, Professor of Medicine
at the Liver Research Unit, Chang Gung University and Memorial
Hospital commented, "In this study, we intend to explore
the theory that the immunomodulatory effects of ZADAXIN could
enhance the immune response of HBV patients thereby achieving
higher seroconversion rates for those patients using lamivudine
to suppress the hepatitis B virus. We expect to observe a
higher response rate from the two drugs combined than from
the separate response rates of each drug alone, therefore
demonstrating a more effective treatment option for patients
suffering from chronic hepatitis B." The hepatitis B
virus is one of the world's most prevalent blood borne chronic
infectious diseases. The World Health Organization estimates
that more than 350 million people worldwide, predominantly
in Asia, are chronically infected with the hepatitis B virus.
Combination therapy using ZADAXIN is also
being studied in clinical trials with pegylated interferon
for the treatment of hepatitis C as well as with the chemotherapy
drug decarbazine (DTIC) for the treatment of malignant melanoma.
Similar to Dr. Liaw's study, these clinical trials are using
ZADAXIN in combination with approved drugs with the objective
of achieving higher response rates compared to current therapy.
ZADAXIN is a pure synthetic preparation of thymosin alpha
1, a natural substance that circulates in the body and is
instrumental in the immune response to fight viral infections
and certain cancers. In over six years of commercial use and
over a decade of clinical development, ZADAXIN, either used
alone or in combination with anti-viral and anticancer drugs,
has not produced any reported significant side effects or
toxicities. 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 is targeting
to file a New Drug Application in Japan for ZADAXIN as a monotherapy
for the treatment of chronic hepatitis B by the end of 2004.
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 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 triple therapy
pilot clinical trial in Mexico. 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.
The information in this press release contains
forward-looking statements including expectations and beliefs
regarding the outcome of the hepatitis B study in Taiwan;
the timing, number of patients enrolled and completion of
enrollment for the study; the timing of filing of SciClone's
Japanese New Drug Application and the fact that the experimental
or clinical data described or compared may imply certain actual
results in larger patient populations. 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, goals, 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, actual results could differ materially
and adversely from those expressed in any forward-looking
statements as a result of various factors, including the progress
or failure of the hepatitis B study in Taiwan, the statistical
significance of data obtained from the study, unexpected results
from the interaction of ZADAXIN in combination with lamivudine,
the potential for receipt of data that is inconclusive or
contradictory, the speed with which patients are enrolled
in the study, competition for enrollment of patients meeting
a particular patient profile, ability to enroll a sufficient
number of eligible patients to yield statistically significant
results, maintenance of the sufficiency and eligibility of
the enrolled patient population, unexpected delays in preparation
of the Japanese New Drug Application, delays in analyzing
and synthesizing data obtained from SciClone's phase 3 hepatitis
B clinical trial in Japan, the fact that experimental data
and clinical results derived from studies with a limited group
of patients may not be predictive of the results of larger
studies and the fact that comparisons between clinical trials
or studies conducted under varying conditions cannot be relied
upon as conclusive evidence as to relative therapeutic benefit,
as well as other risks and uncertainties described in SciClone's
filings with the Securities and Exchange Commission.
Contact:
SciClone Pharmaceuticals Richard A. Waldron, 650-358-3437
Source: SciClone Pharmaceuticals
Back to top
No
'Safe' Alcohol Intake Found with Hepatitis C
Source: Reuters Health
NEW YORK--- Fibrous changes in the liver
caused by hepatitis C infection are worsened with any level
of alcohol consumption, a study shows. However, there may
be trade-off between benefits and risk with low alcohol intake,
according to the report in the journal Hepatology.
Heavy alcohol consumption may contribute
to the progression of hepatitis C-related liver disease, the
authors explain, but light alcohol intake has not been shown
to do so and may, in fact, bestow other health benefits.
To look at this issue, Dr. Alexander Monto
and colleagues from University of California at San Francisco
compared liver biopsies and detailed records of daily alcohol
intake from 800 patients with chronic hepatitis C virus infection.
The researchers found that there was a
range of liver damage severity in each category of alcohol
intake, though overall liver fibrosis was greater in patients
who drank heavily than in those who did not.
The findings were somewhat different in
women, the investigators report. Their fibrosis scores were
lower, and the association between alcohol intake and fibrosis
was less clear.
"One important question has been:
is there a 'safe' level of alcohol intake in patients with
chronic HCV infection?" Monto's team writes. "This
study does not find this to be the case."
They point out, "Light and moderate
intake exert less of an effect on fibrosis than heavy intake,
however, and may indeed have minimal or no effect."
Balancing this "small risk of liver
disease progression against potential cardiovascular benefit
may be particularly pertinent to middle-aged men, who worldwide
constitute the majority of patients with HCV, and who are
also at high risk for cardiovascular disease," the researchers
point out.
They conclude that risks and benefits should
be individually assessed for each patient.
SOURCE: Hepatology, March 2004.
Back to top
April 15th, 2004
Results
of Largest Controlled Clinical Trial in Hepatitis B "e"
Antigen-negative Patients; Resistance Analysis
and Post-Seroconversion Data Presented
Source: Business Wire
BERLIN -- Gilead Sciences today announced
144-week data from a clinical trial (Study 438) of its oral
antiviral drug Hepsera® (adefovir dipivoxil 10 mg) in
patients with hepatitis B "e" antigen-negative/anti-hepatitis
B "e" positive (HBeAg-negative/anti-HBe positive,
or precore mutant) chronic hepatitis B virus. HBeAg-negative
hepatitis B is a mutant strain of the hepatitis B virus (HBV)
that lacks the ability to produce the envelope ("e")
antigen. In this study, patients treated with Hepsera showed
progressive reductions in serum HBV DNA replication and sustained
ALT normalization through 144 weeks of treatment. The development
of Hepsera-related resistance mutations was delayed and infrequent
among patients treated for 144 weeks. Study results were presented
today at the 39th Annual Meeting of the European Association
for the Study of the Liver (EASL) in Berlin, Germany.
It is estimated that more than 400 million
people worldwide have chronic hepatitis B, which is caused
by infection with the hepatitis B virus. One quarter to one
third of these individuals develop progressive liver disease,
which can lead to cirrhosis and/or liver cancer. Approximately
one million people die annually from complications of chronic
hepatitis B, making it one of the leading causes of death
worldwide. HBeAg-negative chronic hepatitis B infects approximately
14 to 24 percent of chronic hepatitis B carriers in North
America and Europe, and is most prevalent in countries of
the Mediterranean and Southeast Asia, where between 30 and
80 percent of chronic hepatitis B patients are estimated to
be infected with this strain.
"Long-term antiviral therapy is typically
needed to control HBeAg-negative chronic hepatitis B, and
high rates of viral resistance can limit other treatment options,"
said Professor Stephanos Hadziyannis, MD, Department of Medicine,
Henry Dunant Hospital, Athens, Greece, and a lead investigator
for Study 438. "The durable antiviral efficacy, good
tolerability profile and low rate of resistance we continue
to see in this study suggest that Hepsera is a valuable treatment
option for patients with HBeAg-negative hepatitis B."
Study 438 Design
The efficacy, tolerability and safety data through 144 weeks
from Study 438 were presented today by Dr. Hadziyannis (Oral
Presentation #46). This 96-week randomized, double-blind,
placebo-controlled clinical trial was designed to evaluate
the long-term safety and efficacy of Hepsera in patients with
HBeAg-negative chronic hepatitis B and compensated liver function.
Following 96 weeks, patients treated with Hepsera during the
second year of the study were offered the drug for up to three
additional years. This study was conducted in Australia, Canada,
France, Greece, Israel, Italy and Southeast Asia. To date,
it is the largest placebo-controlled clinical trial in HBeAg-negative
patients.
Three-year Study Results
Among patients who received continuous Hepsera treatment over
144 weeks (n=70), 79 percent of patients achieved undetectable
levels of serum HBV DNA (less than 1,000 copies/mL, Roche
Amplicor Monitor(TM) PCR assay, compared with 69 percent after
96 weeks. The median reduction in serum HBV DNA levels among
Hepsera-treated patients was 3.63 log10 copies/mL at week
144.
Hepsera also provided sustained improvement
in liver function through 144 weeks, as measured by blood
levels of the liver enzyme alanine aminotransferase (ALT).
The proportion of patients with ALT levels above the upper
limit of normal at baseline whose ALT levels returned to normal
at 144 weeks was 88 percent (n=62).
The safety profile of Hepsera over 144
weeks was consistent with that seen over 48 weeks, which was
similar to placebo. The most common adverse reactions considered
at least possibly related to Hepsera treatment through the
third year of the study were headache, abdominal pain and
asthenia (weakness). Three patients had an increase in serum
creatinine of greater than or equal to 0.5 mg/dL from baseline
by week 144. All cases resolved, one while continuing Hepsera
therapy and two with discontinuation of Hepsera therapy. No
patients had a serum phosphorus level less than 1.5 mg/dL
through 144 weeks.
Probability of Resistance at 144
Weeks
Data further characterizing the long-term resistance profile
of Hepsera were also presented today at EASL by Dr. Shelly
Xiong of Gilead Sciences (Oral Presentation #57). To determine
the incidence of Hepsera resistance after 144 weeks of treatment,
data were analyzed from five clinical studies, including two
pivotal studies of the drug. This analysis included 629, 293
and 167 patients who received 48, 96 and 144 weeks of Hepsera.
Two mutations (rtN236T and rtA181V) in the viral polymerase
have been associated with resistance to the drug. The cumulative
probability of developing resistance after 144 weeks of treatment
with Hepsera across these five studies remains low (3.9 percent),
based on this analysis using the life table method. Through
48 weeks of treatment no Hepsera-related resistance mutations
were identified and among patients treated for 96 weeks, less
than 2 percent (1.6 percent) developed resistance. Resistance
surveillance will continue for up to five years in long-term
clinical efficacy and safety studies.
Durability of Seroconversion after
Hepsera Discontinuation
To evaluate the durability of hepatitis B "e" antigen
seroconversion following treatment with Hepsera, patients
with compensated liver function who had undergone seroconversion
in a prior clinical study (patients were from Studies 437
and 412) were enrolled in a long-term off-treatment follow-up
study (Study 481). Seroconversion was defined as both the
disappearance of hepatitis B "e" antigen (HBe-antigen
negative), a marker of HBV replication, and the appearance
of antibodies specific for "e" antigen (HBe-antibody
positive). Data from an interim analysis of 66 patients were
described today in a poster presentation (Presentation #424).
In this study, seroconversion was shown to be durable in 91
percent of patients following discontinuation of Hepsera.
Patients were followed for a median of 55 weeks after stopping
treatment with Hepsera.
About Hepsera
Hepsera, the first nucleotide analogue for the treatment of
chronic hepatitis B, is administered as a once-daily 10 mg
tablet and works by inhibiting HBV DNA polymerase, an enzyme
involved in the replication of the virus in the body. To date,
Hepsera has been studied in 35 clinical trials and has been
prescribed to approximately 24,000 patients. Hepsera is now
available in the United States and 13 countries in Europe.
In April 2002, Gilead signed a licensing agreement with GlaxoSmithKline
(GSK), granting to GSK rights to commercialize Hepsera in
Asia, Latin America and other territories. Hepsera has been
launched in five Asian markets to date, including Hong Kong
and Singapore.
In the United States, Hepsera is indicated
for the treatment of chronic hepatitis B in adults with evidence
of active viral replication and either evidence of persistent
elevations in serum aminotransferases (ALT or AST) or histologically
active disease.
In the European Union, Hepsera is indicated for the treatment
of chronic hepatitis B in adults with compensated liver disease
with evidence of active viral replication, persistently elevated
serum alanine aminotranseferase levels and histological evidence
of active liver inflammation and fibrosis; or decompensated
liver disease.
The adverse reactions considered at least
possibly related to treatment reported in 3 percent or greater
of patients in the first 48 weeks in Hepsera pivotal clinical
studies were asthenia, headache, abdominal pain, nausea, flatulence,
diarrhea and dyspepsia. With extended treatment, mild to moderate
increases in serum creatinine were observed uncommonly in
patients with chronic hepatitis B and compensated liver disease
treated with Hepsera for a median of 49 weeks and a maximum
of 109 weeks. Changes in serum creatinine were observed very
commonly in patients with pre- and post-transplantation lamivudine-resistant
liver disease and multiple risk factors for changes in renal
function who were treated with Hepsera for up to 129 weeks,
with a median time on treatment of 19 and 56 weeks, respectively.
Clinical and laboratory evidence of exacerbations of hepatitis
have occurred after discontinuation of treatment with antiviral
therapies for hepatitis B, including Hepsera. Special warnings
and precautions for use are included in the package insert
regarding monitoring of renal function, post-treatment exacerbations
of hepatitis, use in patients with underlying renal impairment,
patients co-infected with HIV, the occurrence of nucleoside
analogue-associated lactic acidosis and severe hepatomegaly
with steatosis.
About Gilead
Gilead Sciences is a biopharmaceutical company that discovers,
develops and commercializes therapeutics to advance the care
of patients suffering from life-threatening diseases worldwide.
The company has six marketed products and focuses its research
and clinical programs on anti-infectives. Headquartered in
Foster City, CA, Gilead has operations in the United States,
Europe and Australia.
This press release includes forward-looking
statements, within the meaning of the Private Securities Litigation
Reform Act of 1995 that are subject to risks, uncertainties
and other factors that could cause actual results to differ
materially from those referred to in the forward-looking statements.
Such risks and uncertainties include the risk that these 144-week
data will not be observed through longer treatment periods
and uncertainty regarding inclusion of these data in the Hepsera
product label. These and other risks are described in detail
in the Gilead Annual Report on Form 10-K for the year ended
December 31, 2003 and in Gilead's Quarterly Reports on Form
10-Q, all of which are on file with the U.S. Securities and
Exchange Commission. All forward-looking statements are based
on information currently available to Gilead and Gilead assumes
no obligation to update any such forward-looking statements.
Hepsera is a registered trademark of Gilead
Sciences, Inc.
For more information on Gilead, please
call the Gilead Public Affairs Department at 1-800-GILEAD-5
(1-800-445-3235) or visit www.gilead.com.
Contact:
Gilead Sciences, Inc. Susan Hubbard, 650-522-5715 (Investors)
Erin Edgley, 650-245-1886 (Media)
Source: Gilead Sciences, Inc.
Back to top
PEGASYS
and COPEGUS Now Offers Benefits in a Wider Range of Hepatitis
C Patients
Source: Roche Press Release
New Data Presented At European Liver
Meeting On Two Multinational Trials
Basel, Switzerland –– New data
from two pioneering hepatitis C (HCV) studies with PEGASYS®
plus COPEGUS® will be presented this week at the 39th
Annual Meeting of the European Association for the Study of
the Liver (EASL) in Berlin. The multinational trials –
one in patients with HIV-HCV co-infection and the other in
HCV patients with persistently normal levels of alanine aminotransferase
(ALT) –demonstrate that PEGASYS plus COPEGUS is an effective,
safe and predictable treatment option.
Final results of APRICOT report highest
ever treatment response in co-infected patients
The final results of APRICOT (AIDS PEGASYS— Ribavirin
International CO-infection Trial) – the largest and
only multinational study evaluating the efficacy and safety
of pegylated interferon combination therapy in people co-infected
with HIV and HCV – found that the combination of PEGASYS
and COPEGUS achieved a 40% sustained virological response
(SVR) – the highest ever reported in a trial of co-infected
patients.
“APRICOT provides the guidance that
we have wanted on how best to treat co-infected patients and
there is no doubt that the combination of PEGASYS and COPEGUS
represents the best we can currently offer this patient population,”
said Dr. Francesca Torriani, Associate Professor of Medicine,
Antiviral Research Centre, University of California at San
Diego and one of the APRICOT lead investigators. “What’s
more, we now have data from this trial on our ability to confidently
predict as early as week 12 of therapy which patients are
likely to achieve a sustained virological response.”
The key APRICOT findings that Dr. Torriani
will present on Sunday, April 18th are:
• 40% of patients treated with PEGASYS plus COPEGUS
achieved an SVR compared to 20% of patients treated with PEGASYS
monotherapy and 12% of patients treated with conventional
interferon/ribavirin.
• Genotype 1 patients treated with PEGASYS plus COPEGUS
achieved a four-fold increase in SVR compared to conventional
interferon/ribavirin (29% vs 7%).
• 62% of genotype 2/3 patients treated with PEGASYS
plus COPEGUS combination therapy achieved an SVR compared
to 20% with conventional interferon/ribavirin.
New APRICOT data identifies patients
most likely to respond
New data will be presented on APRICOT that will help physicians
identify those patients with the best chance of achieving
an SVR. 71% of co-infected patients achieved an EVR following
12 weeks of a fixed 180µg/week dose of PEGASYS and 800mg
daily of COPEGUS (ribavirin), and of those, more than half
(56%) achieved an SVR. Among patients with the more difficult-to-treat
HCV genotype 1, 45% who had an EVR went on to achieve a sustained
virological response. The ability to tell patients at week
12 if their treatment is likely to generate an SVR, is now
recognized as having an important role in the motivation of
patients to start with, and stay on, therapy.
Real world patient population in
APRICOT
The patients in this landmark study were predominantly male,
middle-aged with stable HIV disease. However, patients had
a wide range of HIV status; the majority were on anti-retroviral
therapy and they had very high HCV viral loads (10-15 million
copies/ml). The very low (12%) response achieved by patients
to the arm receiving conventional interferon combination therapy
is illustrative of the challenging nature of the co-infection
present in these patients.
European Union contributes nearly
half the patients
422 of the 868 patients randomized in APRICOT came from 11
European Union countries – a total of 19 countries participated.
These patients were randomized to receive either PEGASYS 180µg
once weekly plus COPEGUS 800mg daily; PEGASYS 180µg
monotherapy once weekly (plus placebo COPEGUS tablets), or
conventional interferon alfa-2a 3MIU three times a week in
combination with ribavirin 800mg daily, all for 48 weeks.
New data on quality of life from
second landmark trial in patients with normal ALT
A substantial proportion of hepatitis C patients have ‘normal’
levels of ALT (an enzyme present in the blood used historically
as a marker for liver injury and disease). Because these levels
are ‘normal’, these patients were traditionally
considered to have ‘mild’ hepatitis and therefore
did not need to be treated. More recently, however, there
has been a growing awareness that ALT is actually a poor marker
of liver disease. Indeed, all patients in this trial had evidence
of liver inflammation and nearly one third had some degree
of fibrosis.
In the only global trial in this group
of patients, 514 patients were randomized to receive either
PEGASYS 180µg once weekly plus COPEGUS 800mg daily for
either 24 or 48 weeks, followed by a 24-week treatment-free
follow-up period. A third arm was an untreated control group,
since no treatment was considered the standard of care at
the time the study was designed.
The key trial findings were:
• Overall 52% of hepatitis C patients with ‘normal’
ALT levels achieved an SVR while none in the control arm did.
These results are consistent with the excellent results seen
in other patient populations treated with PEGASYS plus COPEGUS.
• 72% of PEGASYS patients infected with genotypes 2
or 3 who were treated for 24 weeks and 40% of PEGASYS patients
infected with the ‘difficult-to-treat’ genotype
1 who were treated for 48 weeks achieved an SVR.
New data presented at EASL noted
that:
• Those who achieved an SVR reported a better QoL including
reduced fatigue than both the untreated control group and
those who failed to achieve an SVR.
• Those patients who failed to achieve an EVR following
12 weeks of therapy were highly unlikely to achieve an SVR.
As in other HCV patient groups, this provides an early and
meaningful time point for physicians and patients to discuss
the benefits of continuing with treatment if viral eradication
may not be achieved.
“The results of this trial are very
important because until now it was not clear if there were
benefits to treating these patients – which account
for about 30% of patients with chronic hepatitis C,”
said Professor Stefan Zeuzem, from Saarland University, Homburg,
Germany. “Now, we know these patients can be effectively
treated like other patients with hepatitis C and experience
improvements in their quality of life.”
New trial underway by Roche in
another difficult-to-treat group of patients
Recently Roche announced the launch of the first global trial
to study the efficacy of PEGASYS plus COPEGUS in another difficult-to-treat
patient population: hepatitis C patients who failed to respond
to peginterferon alfa-2b plus ribavirin combination therapy.
This trial is known as REPEAT, which stands for "Retreatment
with PEGASYS in patients not responding to prior peginterferon
alfa-2b/ribavirin combination therapy". The REPEAT study
will evaluate the efficacy and safety of the combination of
PEGASYS and COPEGUS given for a longer, 72-week period, as
well as examining the role of an induction regimen in this
treatment- resistant population.
Close to 1,000 patients will participate in this study from
Europe, North America and Latin America.
About PEGASYS
PEGASYS, a new generation hepatitis C therapy that is different
by design, provides significant benefit over conventional
interferon therapy in patients infected with HBV and HCV.
The benefits of PEGASYS are derived from its new generation
large 40 kilodalton (KD) branched-chain polyethylene glycol
(PEG) construction, which allows for sustained drug levels
over the course of a full week. PEGASYS also distributes more
readily to the liver (the primary site of infection) than
conventional interferon. In HCV PEGASYS provides superior
efficacy compared to conventional interferon combination therapy
in HCV patients of all genotypes. PEGASYS is the only pegylated
interferon available as a ready-to-administer solution. Each
weekly subcutaneous injection contains 180mcg of pegylated
interferon alfa-2a (40KD) which is the approved dose for all
patients, regardless of body weight.
All trademarks used or mentioned in this
release are legally protected.
Film footage is available for broadcast
journalists from The NewsMarket at www.thenewsmarket.com.
Video is compressed in MPEG2 and is available for download
to your FTP server.
REFERENCES:
•Torriani FJ, Rockstroh J, Rodriguez-Torres
M, et al. Final week-72 results of the AIDS Pegasys Ribavirin
International Co-infection Trial (APRICOT): A randomized,
partially-blinded, multinational comparative trial of peginterferon
alfa-2a (40KD) (PEGASYS®) plus ribavirin (RBV) (COPEGUS®)
vs interferon alfa-2a (IFN) plus RBV in the treatment of HCV
in HIV/HCV co-infection. EASL oral presentation, 2004.
•M. Rodriguez-Torres,
Torriani FJ, Lissen E, et al. Early Prediction of Sustained
Virological Response (SVR) During Treatment with Peginterferon
Alfa-2a (40KD) (PEGASYS) Plus Ribavirin (RBV) (COPEGUS) In
Patients With HCV/HIV Co-infection: Results From The AIDS
PEGASYS Ribavirin International Co-Infection Trial (APRICOT)
Study. EASL abstract, 2004.
•O’Brien
C, Wintfeld N, Patel KK, et al. The impact of sustained virological
response (SVR) on health-related quality of life (HRQL) in
patients with chronic hepatitis C (CHC) and persistently normal
ALT levels (PNALT) treated with peginterferon alfa-2a (PEGASYS®)
and ribavirin (COPEGUS®). EASL abstract, 2004.
•Pockros PJ,
Diago M, Gane E, et al. Early prediction of sustained virological
response (SVR) during treatment with peginterferon alfa-2a
(40KD) (PEGASYS®) plus ribavirin (RBV) (COPEGUS®)
in patients with chronic hepatitis C (CHC) and persistently
normal alanine aminotransferase (ALT) levels: Results of a
multinational trial. EASL abstract, 2004.
Back to top
The
Tainted-Blood Scandal Lives On
Andre Picard
Public Health Reporter
Source: www.theglobeandmail.com
Ten years ago, public hearings began into
the tainted-blood tragedy, one of Canada's most devastating
public-health fiascos. About 2,000 hemophiliacs and transfusion
recipients contracted HIV-AIDS and another 10,000 or so were
infected with the hepatitis C virus (HCV) from contaminated
blood and blood products.
In that decade, much has changed, thanks,
in large part, to Mr. Justice Horace Krever's searing dissection
of what went wrong and his pointed recommendations on how
to make amends.
Canada has a new, better blood system.
Health Canada takes its regulatory function more seriously.
The Canadian Patient Safety Institute has been created. The
Canadian Public Health Agency is under construction.
But, for the victims of tainted blood,
has justice been done?
One of Judge Krever's central recommendations
was that everyone who suffers "serious adverse consequences
from the administration of blood components or blood products"
-- past, present and future -- should receive financial compensation.
This no-fault approach, he said, was the surest, most cost-efficient
way to provide help to those who were harmed.
The veteran judge cautioned that the alternative
-- using litigation to determine who was wronged and to what
degree, or creating compensation programs for specific groups
in a piecemeal fashion -- was a recipe for disaster.
Yet this is precisely what happened. Compensation
programs were created for those infected with HIV-AIDS, and
they were modified when there was too much media attention
or a worrisome lawsuit.
Then the forgotten victims -- those with
HCV -- came along. This was the group Judge Krever had in
mind when he said no-fault was the way to go. But governments
were terrified by the number of potential claimants with HCV
-- by some estimates at the time as many as 60,000.
Governments ignored Judge Krever's sage
counsel and decided to compensate people infected between
1986, when many U.S. blood banks started testing for HCV,
and 1990, when Canada actually began testing. This, despite
the fact that it became increasingly obvious that the cutoff
dates were arbitrary: A surrogate test for HCV was available
as early as 1981 and there were still some infections after
testing was implemented in 1990.
It was a short-sighted, money-driven decision,
eerily similar to the kind of decisions that caused so many
people to be infected by tainted blood in the first place.
With much fanfare, and no small measure
of hypocrisy, $1.1-billion was set aside to settle lawsuits
from 1986-90 victims. It was believed by then that there were
about 22,000 potential claimants, but that number is now thought
to be still lower.
Today, most of that money is sitting in
a trust fund. So far, $265- million in payments have been
approved to claimants. The fund has probably generated more
than that from its investments, but we can only guess because
even basic information about how $1-billion in tax dollars
is being disbursed is a tightly guarded secret. Without a
doubt, the biggest beneficiaries have been lawyers, actuaries
and accountants. In the first year of the program, lawyers
were paid $53- million, and administration fees topped $9-million.
There have been 8,851 applications for
compensation approved, but probably only a fraction of those
are from victims infected by tainted blood, the rest being
family members and others. Again, the fund administrators
refuse to say for sure. Regardless, only a fraction of the
expected 22,000 claimants in the 1986-90 period have come
forward.
That tells us two things: There are likely
only a few thousand other potential claimants in the pre-1986/post-90
group, and there is plenty of money available to compensate
them.
What possible justification can there be
to not do so? To date, Ontario, Quebec, Manitoba and B.C.
have come around and provided some compensation to the HCV
sufferers excluded from the settlement. But the inequities
are glaring. Why are Ontarians eligible for help, but not
Nova Scotians?
Judge Krever made clear that the tainted-blood
scandal had its roots in prevarication, misplaced penny-pinching
and a patronizing, secretive attitude toward the public --
the victims in particular.
Sadly, those characteristics remain in
the handling of the more than $1-billion in blood money and,
as a result, the tainted-blood scandal lives on.
Back to top
April 16th, 2004
PEGASYS®
More Effective than Lamivudine, the Drug Most Commonly Used
in Difficult-to-Treat Chronic Hepatitis B
Source: Roche Press Release
HBeAg-negative HBV accounts for over 80
per cent of patients in Southern Europe
Basel, Switzerland –– A landmark
international trial in patients with HBeAg-negative chronic
hepatitis B, the most difficult-to-treat form of hepatitis
B, has concluded that PEGASYS monotherapy is more effective
than lamivudine, the current standard treatment for this condition.
Moreover the data showed that the combination of lamivudine
to PEGASYS did not improve response rates over PEGASYS alone.
These results will be presented at the 39th Annual Meeting
of the European Association for the Study of Liver Disease
(EASL) in Berlin.
The efficacy of PEGASYS is further reinforced
by new data showing that PEGASYS monotherapy produced a beneficial
histological response (improvement in the health of the liver)
in nearly half (47%) of the patients. Also in a small group
of patients, PEGASYS monotherapy achieved the rare occurrence
of HBV surface antigen loss and/or seroconversion to anti-HBs
– the most complete response possible to treatment and
indicative of complete remission.
“These results are extremely encouraging
for patients with this form of chronic hepatitis B,”
said Professor Patrick Marcellin, Hepatologist at the Hôpital
Beaujon, Clichy, France and the lead investigator for the
study. “Until now, conventional interferon or lamivudine
have been the first-line treatments for chronic hepatitis
B. However this trial indicates that 24 weeks after cessation
of treatment, PEGASYS had superior efficacy to lamivudine,
which has been the most commonly used therapy for chronic
hepatitis B. This points to there being a strong role for
this particular pegylated interferon in the treatment in chronic
hepatitis B,” added Professor Marcellin.
This Phase III study, the largest and only
multinational study of pegylated interferon in patients with
HBeAg-negative chronic hepatitis B, is also the first large-scale
head-to-head study to compare Roche’s PEGASYS against
lamivudine.
About the study
A total of 537 patients from 13 countries were enrolled in
the study. Almost 40% were Caucasian and all had HBeAg-negative
chronic hepatitis B and raised blood levels of ALT, a specific
liver enzyme serving as a marker for liver inflammation. Patients
were treated for 48 weeks with either PEGASYS 180µg
once weekly plus placebo, lamivudine 100mg once daily, or
a combination of PEGASYS and lamivudine. Treatment response
was assessed following a 24-week treatment-free follow-up
period.
The study examined the effect of treatment
on ALT and HBV DNA levels (primary endpoints), the condition
of the liver (liver histology) and HBsAg response. HBsAg response
(loss of the HBV HBsAg and the development of antibodies to
HBsAg) is a very rare event indicative of a complete remission.
Key findings
At the end of the treatment-free follow-up period, it was
found that:
• 43% of patients treated with PEGASYS monotherapy reduced
their hepatitis B viral DNA to less than 20,000 copies per/ml
compared to only 29% of those treated with lamivudine. This
result is highly statistically significant. The combination
of PEGASYS and lamivudine yielded a reduction in hepatitis
B viral DNA in 44% of patients, demonstrating that the addition
of lamivudine to PEGASYS does not improve the treatment outcome.
• PEGASYS had a better impact on normalisation of liver
transaminases than lamivudine: 59% of patients treated with
PEGASYS had their elevated ALT levels return to normal; compared
to only 44% of lamivudine-treated patients. The combination
of PEGASYS and lamivudine (60%) was not statistically different
to PEGASYS alone.
• HBsAg response – an extremely rare finding –
was reported in 12 patients treated with PEGASYS (with or
without lamivudine) and none of the patients treated with
lamivudine alone. Although the numbers are low, clinically
this is a very significant result as it is indicative of complete
remission.
• Patients who showed a reduction in hepatitis B viral
DNA levels to less than 20,000 copies/ml, or whose ALT levels
returned to normal, showed an improvement in their liver histology.
About Hepatitis B
Hepatitis B is a blood-born virus that attacks the liver and
is the most common serious liver infection in the world.
Despite a highly effective vaccine, more
than two billion people have been infected with hepatitis
B and 350 million people have chronic infection, which can
be easily transmitted by blood-to-blood contact, during birth,
sex, and by sharing needles. Hepatitis B and C rank among
the top four causes of cancer deaths in most countries in
Asia and the Western Pacific rim. For those chronically infected
with hepatitis B, treatment is the only option.
About HBeAg-negative HBV
HBeAg-negative chronic hepatitis B, also known as ‘variant’
or ‘pre-core mutant’ hepatitis B, is caused by
a genetic mutation to the virus. Patients infected with HBeAg-negative
chronic hepatitis B are more likely to have severe destructive
inflammatory changes to their liver and fibrosis when they
first see their physician than those infected with the HBeAg-positive
disease. Patients typically relapse after treatment is stopped.
HBeAg-negative chronic hepatitis B accounts for approximately
40% of cases in the US and over 80% of cases in Southern Europe.
About PEGASYS
PEGASYS, a new generation hepatitis therapy that is different
by design, provides significant benefit over conventional
interferon therapy in patients infected with chronic hepatitis
B and C. The benefits of PEGASYS are derived from its new
generation large 40 kilodalton branched-chain polyethylene
glycol (PEG) construction, which provides sustained drug levels
over the course of a full week. PEGASYS also distributes more
readily to the liver (the primary site of infection) than
conventional interferon. In chronic hepatitis C, PEGASYS provides
superior efficacy compared to conventional interferon combination
therapy in HCV patients of all genotypes. PEGASYS is the only
pegylated interferon available as a ready-to-administer solution.
Each weekly subcutaneous injection contains 180µg of
pegylated interferon alfa-2a which is the approved dose for
all patients, regardless of body weight. In a Phase II trial
in HBeAg-positive chronic hepatitis B, PEGASYS has proven
more effective than conventional interferon. A larger scale
Phase III trial in patients with HBeAg-positive chronic hepatitis
B is currently underway.
Roche in hepatitis
Roche is committed to the viral hepatitis disease area, having
introduced Roferon-A for hepatitis B and C, followed by PEGASYS
in hepatitis C and now PEGASYS also demonstrates superior
efficacy over current treatments: conventional interferon
and lamivudine in hepatitis B. Roche has also launched its
own brand of ribavirin, COPEGUS®, to be used in conjunction
with Roferon A or PEGASYS for HCV. Roche also manufactures
HBV and HCV diagnostic and monitoring systems: The COBAS AMPLICOR™
Test, and the AMPLICOR™ MONITOR Test, two testing systems
used to detect the presence of, and quantity of, HBV DNA or
HCV RNA in a person’s blood.
All trademarks used or mentioned in this
release are legally protected.
NOTES TO THE EDITOR:
• This trial was conducted in the following countries:
o Europe: France, Germany, Greece, Italy, Poland, Spain, Switzerland,
Turkey, North America: Canada
o Asia: China, Hong Kong, Taiwan, Thailand
o Australasia: New Zealand
New guidelines on HBV were recently developed by the European
Association for the Study of Liver (EASL). Conventional interferon
monotherapy was recommended as the first therapeutic approach
when treating these patients. The EASL Jury noted, however,
that the optimal treatment of hepatitis B will require regular
revision in light of new data.
REFERENCES:
i Marcellin P, Lau G, Bonino F,
et al. Peginterferon alfa-2a (40KD) (PEGASYS®) monotherapy
is more effective than lamivudine monotherapy in the treatment
of HBeAg-negative chronic hepatitis B: 72-week results from
a phase III, partially double blind study of PEGASYS®
alone vs PEGASYS® plus lamivudine vs lamivudine. Presented
at the 39th Annual Meeting of the European Association for
the Study of the Liver (EASL). 14th-18th April 2004, Berlin.
ii Chu, CM. Natural History of Chronic Hepatitis B Virus
Infection in Adults with Emphasis on the Occurrence of Cirrhosis
and Hepatocellular Carcinoma. J Gastroenterol. Hepatol. 2000;15
(suppl.):E25-30.
iii EASL International Consensus Conference on Hepatitis
B. 13-14 September, 2002: Geneva, Switzerland. Consensus statement
(short version). J Hepatol, 2003.38:533-40.
Back to top
Vertex
Pharmaceuticals (VRTX) Reports Data on Investigational Hepatitis
C Therapies Suggesting Potential For Novel Treatment Approaches
Source: PRNewswire
BERLIN, -- New data for proprietary investigational
antiviral therapies for hepatitis C virus (HCV) infection
being developed by Vertex Pharmaceuticals Incorporated were
presented today at the Annual Meeting for the European Association
for the Study of the Liver (EASL) in Berlin, Germany. The
clinical and preclinical data presented highlight the potential
of these therapies to address significant unmet medical needs
in the treatment of HCV.
Vertex's extensive drug development portfolio
includes two different approaches for advancing the future
standard-of-care in HCV. Merimepodib, Vertex's lead oral therapy
targeting HCV, is being developed in combination with the
current therapeutic standard, pegylated interferon alpha (peg-IFN)
and ribavirin, with the goal of enhancing antiviral efficacy
and increasing the proportion of patients who achieve a sustained
response to treatment. Vertex is also developing VX-950, an
investigational HCV protease inhibitor and one of the most
advanced of a new class of direct antiviral agents for the
treatment of chronic HCV infection. Vertex owns worldwide
development and commercialization rights for both merimepodib
and VX-950.
In a poster session at EASL today, clinical
investigators presented results for patients enrolled in the
extension phase of a pilot Phase IIa study designed to evaluate
the safety and tolerability of merimepodib in combination
with peg-IFN and ribavirin in a treatment-refractory population.
Additionally, in oral presentations at EASL, Vertex scientists
reported preclinical data highlighting the promising antiviral
profile of VX-950, including in vitro data assessing the antiviral
activity of VX-950 in combination with interferon alpha.
"The results presented at EASL provide
strong support for initiating late- stage clinical development
of merimepodib, as well as the first clinical studies of VX-950,"
stated John Alam, M.D., Senior Vice President for Drug Evaluation
and Approval at Vertex. "These are key milestones for
Vertex and its interest in providing new therapies in HCV,
and are anticipated in 2004. Vertex's goal is to commercialize
innovative therapies that will provide additional options
for patients and enhance HCV clinical care."
Merimepodib Results and Clinical Plans
In 2003, Vertex completed the treatment arms of a placebo-controlled
triple combination Phase II study of merimepodib (MMPD) in
combination with peg-IFN and ribavirin. This trial was designed
to evaluate the safety of the triple combination in 31 patients
with genotype 1 infection who did not respond to a previous
course of interferon alpha in combination with ribavirin.
The study provided for six months of treatment, with an optional
six-month extension phase for patients who responded to therapy.
Data presented by clinical investigators in 2003 demonstrated
that the triple combination of MMPD + peg-IFN + ribavirin
was well-tolerated and did not appear to exacerbate the incidence
of hematological toxicities associated with peg-IFN and ribavirin
treatment. Study results also indicated that the addition
of merimepodib enhanced the antiviral activity of the peg-IFN
+ ribavirin combination at 24 weeks.
In a poster presented at EASL today, clinical
investigators presented data on 11 patients (three subjects
receiving placebo + peg-IFN + ribavirin and eight subjects
receiving MMPD + peg-IFN + ribavirin) who were eligible to
continue into the extension phase of the study. Ten patients
completed 48 weeks of treatment. At the end of 48 weeks of
treatment, the safety profile of MMPD was similar to the core
24-week study, and the majority of adverse events reported
were consistent with the known side effect profile of peg-IFN
and ribavirin. One of three patients in the placebo group
and three of seven patients receiving MMPD who completed the
extension phase achieved a sustained viral response at week
72 (24 weeks post-treatment). Based on the Phase IIa results,
Vertex is planning to initiate larger studies to evaluate
the ability of merimepodib to increase sustained viral response
rates (SVR) in HCV- infected patients. These larger studies
may involve, as before, an initial treatment period with MMPD
in combination with peg-IFN and ribavirin, but followed by
continued treatment with peg-IFN and ribavirin alone, a clinical
approach suggested by the clinical and preclinical data to
optimize the SVR.
"Merimepodib demonstrated a good tolerability
profile and showed important signs of antiviral activity in
this study," stated Dr. Patrick Marcellin, Professor
of Medicine at University of Paris VII, and the lead investigator
for the study. "Genotype 1 HCV is associated with the
lowest response to therapy, and patients who are non-responsive
to prior combination therapy have very limited treatment options
available. These results support larger well- controlled studies
in treatment-refractory patients to evaluate the ability of
merimepodib to effect an increase in sustained viral response
in combination with peg-IFN and ribavirin."
Vertex anticipates initiating in 2004 a
Phase IIb clinical study of merimepodib in patients who are
non-responsive to prior treatment with peg-IFN + ribavirin.
The primary goal of this placebo-controlled study will be
to evaluate the antiviral activity of a triple combination
regimen and to perform an assessment of sustained virologic
response (SVR) rates. SVR is defined as an HCV-undetectable
value at the end of a 24-week post-treatment follow-up period
(week 72).
VX-950 Results and Clinical Plans
In oral presentations at EASL on Thursday and Friday, Vertex
researchers presented a variety of preclinical results highlighting
the emerging profile of VX-950. Vertex researchers demonstrated
that treatment of HCV replicon cells with VX-950 decreased
viral replication by 10,000-fold to undetectable levels; when
the drug was subsequently removed, no rebound of viral replication
was observed, suggesting that the HCV replicon had been eradicated
from the treated cells. A second line of experiments showed
that combination of interferon alpha with VX-950 in the HCV
replicon system allowed scientists to reduce the level of
VX-950 and still obtain the same degree of antiviral potency
obtained with a 5-fold higher concentration of VX-950 alone.
Data presented last year at the AASLD and
International HCV meetings showed that the dominant mutation(s)
selected in the laboratory against VX-950 remained sensitive
to BILN 2061, a protease inhibitor developed by another company
which has shown antiviral activity in HCV patients, and BILN
2061 resistant mutants remained sensitive to VX-950. In the
studies presented at EASL, researchers analyzed minor mutations
that were cross-resistant to VX-950 and BILN 2061 in the laboratory
and found that enzymatic activity of the cross-resistant HCV
protease was reduced approximately 4 to 7-fold, a condition
which could impair the ability of the virus to grow.
"Vertex's leadership position in the
discovery of novel approaches to HCV treatment has been enhanced
by the development of new technologies and approaches for
evaluating the clinical potential of experimental compounds,"
commented Dr. Alam. "The results we have seen with VX-950
confirm our selection of HCV protease as an excellent target
for the development of powerful antiviral therapies and that
VX-950 has the potential of becoming a highly valuable therapeutic
agent for the treatment of HCV patients."
Vertex anticipates that it will initiate
a Phase I clinical trial of VX- 950 in healthy volunteers
in 2004. Positive results from this first Phase I study will
pave the way for the first evaluation of VX-950's antiviral
activity in HCV-infected patients.
Clinical Need and Market Opportunity
in HCV Infection
HCV infection is a serious disease that causes inflammation
of the liver, which may lead to fibrosis and cirrhosis, liver
cancer, and ultimately, liver failure. Chronic hepatitis C
infection afflicts approximately 2.7 million people in the
U.S., many of whom are unaware of their infected status. Current
treatments provide a sustained viral response for only 40
to 50 percent of patients chronically infected with genotype
1 HCV, the most difficult viral strain to treat and the most
common form in the U.S. Patients who are non-responsive to
current HCV therapy have limited treatment options, and clinical
experience suggests that only a very low proportion of such
patients achieve a sustained viral response with subsequent
treatment regimens. HCV may go 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. Vertex co-promotes
the new HIV protease inhibitor, Lexiva(TM), with GlaxoSmithKline.
This press release may contain forward-looking
statements, including statements that (i) Vertex anticipates
commercializing new therapies, including merimepodib and VX-950,
for the treatment of hepatitis C and that merimepodib and
VX-950 each have the potential to address significant unmet
needs in HCV treatment; (ii) merimepodib and VX-950 each hold
promise as part of combination therapy for HCV patients who
have limited treatment options and represents an attractive
commercial opportunity for Vertex; (iii) further clinical
study of merimepodib will be initiated in 2004; and (iv) clinical
study of VX-950 will be initiated in 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 or VX-950 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 either merimepodib
or VX- 950 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
http://www.vrtx.com/.
Vertex Pharmaceuticals Incorporated will
host a conference call on Monday, April 26, 2004 at 5:00 pm
(EDT) to discuss its first quarter 2004 financial results,
at which time it will review and update its HCV product development
programs. The conference call also will be webcast, and the
webcast will be available to all interested parties through
Vertex's website, http://www.vrtx.com/.
To access the webcast, go to the investor center and select
"conference calls." To ensure a timely connection
to the webcast, it is recommended that users register at least
15 minutes prior to the scheduled webcast.
Vertex Contacts: Michael Partridge, Director,
Corporate Communications (617) 444-6108 Lora Pike, Manager,
Investor Relations (617) 444-6755
Vertex Pharmaceuticals Incorporated
CONTACT: Michael Partridge, Director, Corporate Communications,
+1-617-444-6108, or Lora Pike, Manager, Investor Relations,
+1-617-444-6755, both of Vertex Pharmaceuticals Incorporated
Web site: http://www.vrtx.com/
Company News On-Call: http://www.prnewswire.com/comp
/938395.html
Back to top
Metabasis
Therapeutics Reports The Earning Of A Milestone Payment Based
On Continued Development Of Remofovir For The Treatment Of
Hepatitis B
Source: PRNewswire
SAN DIEGO-- Metabasis Therapeutics, Inc.
(Metabasis) announced today that Valeant Pharmaceuticals International
has agreed to pay a $1 million milestone payment to Metabasis
in recognition of a decision to initiate a Phase II clinical
evaluation of remofovir (formerly known as Hepavir B) in patients
with chronic hepatitis B infection. Valeant licensed remofovir,
an orally active prodrug of the proven antiviral agent adefovir,
from Metabasis in October 2001 and is primarily responsible
for the clinical development of the drug. The decision to
proceed with development was based on results recently obtained
from the first clinical evaluation of remofovir in patients
infected with the hepatitis B virus.
About Metabasis
Metabasis Therapeutics, Inc. (http://www.mbasis.com/)
is a biopharmaceutical company focused on the discovery, development
and commercialization of novel small molecule drugs principally
to treat liver diseases and metabolic diseases linked to pathways
in the liver. The company has established a broad product
pipeline targeting large markets with significant unmet medical
needs. Metabasis currently has three internally discovered
product candidates in clinical trials indicated for the treatment
of type 2 diabetes, hepatitis B and primary liver cancer.
Metabasis Therapeutics, Inc.
CONTACT: Paul Laikind, Ph.D., of Metabasis Therapeutics, Inc.,+1-858-622-5550
Web site: http://www.mbasis.com/
Gilead Sciences (GILD) Release: New
Data Support Hepsera's Long-Term Efficacy Against Chronic
Hepatitis B
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April 17th, 2004
Valeant
Pharmaceuticals Presents Details of 24-Week Data for Viramidine
Phase 2 Clinical Trials
Source: PRNewswire
Data Shows a Sustained Reduction in
Viral Titre for All Three Doses of Viramidine, Comparable
to Ribavirin
COSTA MESA, California Valeant Pharmaceuticals
(NYSE: VRX) today presented 24-week data from Phase 2 clinical
trials of Viramidine, a nucleoside (guanosine) analog Valeant
is developing in oral form for the treatment of chronic hepatitis
C (HCV) in conjunction with a pegylated interferon. Valeant
presented its data at the European Association for the Study
of the Liver (EASL) Conference in Berlin, Germany.
The Viramidine Phase 2 study consists of
180 treatment-naïve subjects with chronic HCV. The on-going
study was an open-label, randomized, active control trial,
being conducted at multiple centers in the United States and
with patients stratified by genotype. The study consists of
four demographically comparable treatment groups: Viramidine
400 mg BID, Viramidine 600 mg BID, Viramidine 800 mg BID and
ribavirin 1000/1200 mg daily all in combination with peginterferon
alfa-2a. Treatment duration was based on genotype, with genotypes
two and three receiving 24 weeks of treatment and genotype
one receiving 48 weeks of treatment, each with a post-treatment
follow-up period of 24 weeks.
The interim 24-week data shows that Viramidine
demonstrates antiviral activity comparable to that of ribavirin,
when used in combination with peginterferon alfa-2a in treatment
naïve patients, but with a lower incidence of anemia.
The data demonstrates a sustained reduction
in HCV RNA of approximately two-and-a-half log(10) for all
three doses of Viramidine, comparable to the ribavirin group
in the same study. The proportion of patients with greater
than or equal to 2 log(10) reduction or non-detectable HCV
RNA was 83 percent for both Viramidine (800-1600 mg/day) and
ribavirin at 24 weeks. The results also show the percent of
patients with non-detectable HCV RNA at 12 weeks and 24 weeks
were similar between all treatment groups.
There were also fewer patients in the Viramidine
groups with anemia (defined as hemoglobin < 10g/dL) when
compared with the ribavirin arm (2 percent versus 24 percent;
p < 0.001). In the Viramidine 400 mg BID and 600 mg BID
dosage groups, defined anemia (hemoglobin < 10g/dL) did
not occur, while there were only two occurrences of anemia
in the 800 mg BID group. Other adverse events were similar
among treatment groups.
Data was presented by Robert Gish, M.D.,
the lead investigator on the Viramidine Phase 2 study and
Medical Director of the Liver Transplant Program at California
Pacific Medical Center in San Francisco.
A Phase 3 clinical trial of Viramidine
compared to ribavirin in combination with pegylated interferon
was initiated in the fourth quarter of 2003 and is ongoing.
The Phase 3 trial compares the 600 mg BID dose of Viramidine
to ribavirin, each in conjunction with pegylated interferon
alpha 2b.
About Valeant
Valeant Pharmaceuticals International (NYSE: VRX) is a global,
publicly traded, research-based specialty pharmaceutical company
that discovers, develops, manufactures and markets a broad
range of pharmaceutical products. More information about Valeant
can be found at www.valeant.com.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements within
the meaning of the federal securities laws relating to expectations,
plans or prospects for Valeant Pharmaceuticals, including
funding and conducting clinical trials and expected research
and development expenses. These statements are based upon
the current expectations and beliefs of Valeant Pharmaceuticals'
management and are subject to certain risks and uncertainties
that could cause actual results to differ materially from
those described in the forward- looking statements. These
risks and uncertainties include market conditions and other
factors beyond Valeant Pharmaceuticals' control, the company's
success in identifying and enrolling patients in the clinical
trials program, the absence of adverse events that would require
the clinical trials to be prematurely terminated, clinical
results that indicate continuing clinical and commercial pursuit
of Viramidine is advisable, and the risk factors and other
cautionary statements discussed in Valeant Pharmaceuticals'
filings with the U.S. Securities and Exchange Commission.
For further information, please contact: Jeff Misakian of
Valeant Pharmaceuticals, +1-714-545-0100, ext. 3309.
Web site: http://www.valeant.com
Source: Valeant Pharmaceuticals International
CONTACT: Jeff Misakian of Valeant Pharmaceuticals, +1-714-545-0100,
ext. 3309, FCMN Contact:
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