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Alan Franciscus
Editor-in-Chief
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In This Issue:
Estrogen's Beneficial Role
in Liver Cancer
Vertex Hepatitis C Drug To Enter Phase IIb In
’04; NDA Filing As Early As ’06
Maxim Pharmaceuticals Awarded Most Innovative
Product Award by UCSD Connect
Roche Reports on Two Major Achievements in Japan,
the World's Second Largest Pharmaceuticals Market
InterMune Announces Presentation of Interim Findings
of the First Clinical Experience of Infergen Plus Actimmune
Combination Therapy in Hepatitis C Nonresponders
XTLbio R&D and Business Development Update
ViroLogic Presents Data Using New Hepatitis C
Virus Drug Resistance Assay
Chiron Grants Nonexclusive HCV License To Boehringer
Ingelheim
Drug Makers Target Hepatitis C Market
December 15th, 2003
Estrogen's Beneficial
Role in Liver Cancer
John C. Martin, Hepatitis Neighborhood
It appears that increased exposure to estrogen
may play a protective role in your risk of developing hepatocellular
carcinoma (HCC), the most common form of liver cancer. That's
the conclusion of a Taiwanese study that looked at how pregnancy
and exposure to estrogen affects liver cancer risk.1
A Common Liver Cancer
Hepatocellular carcinoma can often be the end result of chronic
liver disease caused by hepatitis. This is especially true
if a person is infected with hepatitis in combination with
cirrhosis, a condition in which the liver tissue becomes deformed
as a result of scar tissue.
Hepatocellular carcinoma is a highly malignant
tumor that is difficult to treat, and often can have a negative
outcome. In the U.S., hepatocellular carcinoma accounts for
about 1 percent of all cancers. But it is much more prevalent
elsewhere in the world, accounting for up to 50 percent of
cancer cases. The differences are believed to be due to the
much higher percentage of people who have hepatitis B, which
predisposes the patient to the development of this type of
liver cancer.2
Liver Cancer Therapy
Treatment options for hepatocellular carcinoma vary. When
the tumor is small, and limited to one lobe of the liver,
surgical removal may be an effective option. But when the
tumor is larger or involves more than one lobe of the liver,
a liver transplant may be the only alternative. The cure rate
in either case is about 20-30%.2
According to the study authors, hepatocellular
carcinoma is more common in men than in women, and the theory
is that that is due to women's exposure to estrogen during
their lives.
"It has long been known that there
is a striking male-to-female ratio in the incidence of HCC
throughout the world," said Ming-Whei Yu, Ph.D., director
of the department of Public Health at National Taiwan University
and the study's lead author, in an interview with Priority
Healthcare. "This difference between sexes suggests that
sex steroid hormones may play some role in the development
of HCC."
Evaluating Estrogen's Impact
To determine how increased estrogen levels may lower the risk
of developing liver cancer, Yu and her colleagues assessed
how being pregnant, as well as menopause, may alter the risk.
They enrolled 218 women with hepatocellular
carcinoma, comparing their risk of developing cancer with
729 women without the disease.
In most cases, the investigators found
that exposure to estrogen lowered the risk. "The risk
of HCC was inversely related to the number of full-term pregnancies,
and age at natural menopause," they wrote.
In other words, women who had been pregnant
more often faced a lower risk of developing liver cancer.
The older a woman was when she started menopause, the lower
the risk, as well.
A surgical procedure known as oophorectomy
in younger women, in which one or more ovaries are removed,
was also a risk factor, Yu and her co-investigators found.
Women with a history of hormone replacement
therapy (HRT) use also faced a lower risk of developing liver
cancer in the study. In fact, Yu and her team found an increasingly
lower risk with increasing use of the therapy. But they cautioned
that they were not able to collect more thorough information
about HRT use in this study.
"In conclusion, increased exposure
to estrogen during adulthood may provide a protective effect
against HCC," Yu and her colleagues wrote. That was the
case irregardless of whether the woman had hepatitis or not.
The only exception was in women with hepatitis
who had entered puberty at an earlier age, which exposed them
to estrogen levels earlier. In those cases, the researchers
found that estrogen exposure did not lower the risk of developing
cancer, and in fact was linked with "an elevated disease
risk". Why that is, isn't known, Yu told Priority Healthcare.
By contrast, women without hepatitis who had begun puberty
earlier had no increased risk, Yu and her colleagues found.
So, why does estrogen provide this protection?
Other studies have suggested that the hormone calls up certain
tumor-suppressing genes in the body, Yu said.
Conflicting Research
Other study's findings, however, have been conflicting. Like
the Taiwanese study, doctors in Singapore found estrogen exposure
generally lowers the risk of contracting liver cancer, specifically,
that the breast cancer drug tamoxifen, which blocks the activity
of estrogen, increases the risk.3
The researchers recruited 329 patients
with inoperable liver cancer, dividing them into three groups.
Two groups were given two varying doses of tamoxifen, and
the third group was given a placebo—an ineffective medication—as
a comparison. Neither the researchers nor the patients knew
which medication was being given.
The investigators found that there was
a "significantly higher risk of death" among patients
given higher doses of tamoxifen compared to those given a
placebo.
However, in a Greek study published in
2001, researchers studied how hormone exposure—estrogens
in particular—affected the risk of developing hepatocellular
carcinoma.4 They compared a group of 50 female liver cancer
patients with 62 women who did not have cancer.
The researchers found that women with liver
cancer had generally entered puberty at a younger age and
were significantly older by the time they reached menopause.
"Age at menopause remained an important and significant
predictor, increasing the risk of hepatocellular carcinoma
24% for each later year of menopause," the investigators
wrote. "For each year that menarche [start of menstruation]
was delayed, risk of hepatocellular carcinoma declined 21%."
Study Weaknesses
Yu admits some limitations with her study, including the fact
that women provided information on their estrogen use and
reproductive history through questionnaires, increasing the
possibility that their answers may not have been precise.
Because of that, Yu says while the findings
are "intriguing, more studies are needed to confirm these
results."
In the meantime, she and her colleagues
are conducting a new study to determine what causes this prophylactic
effect of estrogen.
1. Yu MW et al. Role of reproductive factors
in hepatocellular carcinoma: Impact on hepatitis B- and C-related
risk. Hepatology 2003 Dec 38(6):1393-1400.
2. American Liver Foundation.
3. Chow PK et al. High-dose tamoxifen in the treatment of
inoperable hepatocellular carcinoma: A multicenter randomized
controlled trial. Hepatology 2002 Nov;36(5):1221-6.
4. Mucci LA et al. Age at menarche and age at menopause in
relation to hepatocellular carcinoma in women. BJOG 2001 Mar;108(3):291-4.
John Martin is a long-time health journalist
and an editor for Priority Healthcare. His credits include
coverage of health news for the website of Fox Television's
The Health Network, and articles for the New York Post and
other consumer and trade publications.
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Vertex Hepatitis
C Drug To Enter Phase IIb In ’04; NDA Filing As Early
As ’06
Pivotal trials for Vertex’ Hepatitis
C treatment merimepodib could begin in 2004, CEO Joshua Boger,
PhD, said.
Merimepodib Phase IIb trial for the treatment
of Hepatitis C in treatment refractory patients is slated
to begin in the second half of 2004; whether or not the trial
could be the basis for an accelerated approval will be decided
in first quarter discussions with FDA, Boger said during an
analyst presentation Dec. 3.
“A patient population such as treatment
refractory patients in Hepatitis C...is almost a tailored
made definition for accelerated approval,” Boger stated.
“Accelerated approval for HIV took
place off Phase IIb studies, so the assumption that before
you’re in pivotal studies you have to call a trial Phase
III simply isn’t the way HIV drugs were developed,”
he added.
“It looks to us that there’s
a possibility that this initial Phase IIb study could be the
beginning, if FDA agreed upon, not just speculative, a pivotal
study,” Boger said. “On the basis of a factual
analysis, this looks to be tailor made for accelerated approval.”
Vertex is developing merimepodib as an
add-on treatment to the current standard of care for Hepatitis
C of peginterferon alfa (Roche’s Pegasys, Schering-Plough’s
PEG-Intron) and ribavirin (Roche’s Copegus, Schering’s
Rebetol).
The company will seek FDA approval of merimepodib
first in the treatment-refractory population; an NDA filing
for that indication is planned for 2006-2007. An sNDA in treatment-naive
patients would be submitted shortly thereafter.
“In the immediate future, going into
2004, we are planning on initiating a Phase IIb study of merimepodib
in a pegylated interferon plus ribavirin non-responder patient
population,” Vertex Senior VP-Drug Evaluation &
Approval John Alam, MD, said.
The Phase IIb study will introduce additional
dosing groups to those previously studied (25 mg and 50 mg).
“We are planning on doing a Phase IIb study...which
would include multiple dose groups, and we may well consider
adding one more dosing group at the higher dosing level from
50 mg b.i.d.,” Alam said.
In Phase II studies, 86% of patients taking
50 mg merimepodib plus interferon and ribavirin responded
to treatment, compared with a 35% response in patients taking
25 mg merimepodib and 35% in patients given placebo in addition
to standard of care.
Vertex also plans to conduct a short-term
study evaluating the effects of merimepodib plus ribavirin
without interferon.
Vertex expects merimepodib should work
with the ribavirin prodrug, Viramidine (guanisine), under
development by Valeant and Schering-Plough. Viramidine has
completed Phase II.
Also under development at Vertex is a protease inhibitor VX-950
“to improve on the overall efficacy level further and
potentially either shorten the duration of treatment or replace
some of the treatment, including, potentially, interferon
alpha, which contributes to many of the side effects seen,”
Alam stated. VX-950 will enter clinical trials in 2004.
Over the long term, Vertex is planning
the development of an oral combination therapy for Hepatitis
C.
Success in the Hepatitis C specialty market
is a core strategy for Vertex. “We’ve decided
that we can win as a small company by deciding to play by
specialty markets, picking those that have the highest amount
of value but small, concentrated, focused specialty populations
driving prescriptions,” Vertex Senior VP-Commercial
Operation Anthony Coles, MD, said.
Hepatitis C “is a great example of
this, the perfect expression of this strategy” with
“the top 10% of the target writing 50% of the prescriptions,”
Coles added. Vertex anticipates it can appropriately leverage
the market with a sales force of 100 reps.
The possibility of generic ribavirin could
improve pricing for merimepodib, Coles suggested. “I
do think we’re aided, potentially, by the arrival of
generic ribavirin. I think there’s still a premium price
opportunity in the market place.” The current standard
therapy is priced between $30,000 and $40,000.
At least three companies – Geneva,
Teva and Three Rivers – have submitted ANDAs for generic
ribavirin (1“The Pink Sheet” Sept. 1, 2003, p.
14).
Source: The Pink Sheet
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Maxim
Pharmaceuticals Awarded Most Innovative Product Award by UCSD
Connect
Business Editors/Health/Medical Writers
BIOWIRE2K
SAN DIEGO--(BUSINESS WIRE)--Dec. 15, 2003--Maxim
Pharmaceuticals, Inc. (Nasdaq NM: MAXM, SSE: MAXM) announced
that it has been awarded the Most Innovative Products Award
for its lead drug candidate.
Ceplene(TM) in the category of Biotechnology
R&D, in the 16th annual competition sponsored by University
of California, San Diego CONNECT. Maxim's nomination for Ceplene,
which is in late-stage clinical development and pending European
Union approval, focused on the unique mechanism and breakthrough
potential of the drug candidate in a wide range of life-threatening
cancers and chronic liver diseases.
Winners in six technology categories, including biotechnology,
were selected based on their ability to demonstrate their
products technology's innovation, technological advancement
and potential for commercial success. The nominees were reviewed
by a panel of distinguished judges who are expert their fields.
UCSD CONNECT, a globally recognized, university-based non-profit
organization fostering entrepreneurship in the San Diego region,
hosts these awards to recognize outstanding companies that
exemplify the region's reputation for high-caliber discoveries,
innovative technologies and creative product development.
"We are honored to have received the
Most Innovative Products Award for Ceplene, selected from
an outstanding group of products for this competition,"
said Larry G. Stambaugh, Maxim's Chairman and Chief Executive
Officer. "It is a testament to the Maxim associates and
global collaborators who have combined scientific originality
and a disciplined approach to product development to advance
Ceplene from concept to late-stage clinical trials and pending
commercialization for life-threatening diseases."
Maxim Overview
Maxim Pharmaceuticals is a global biopharmaceutical
company with a diverse pipeline of therapeutic candidates
for life-threatening cancers and liver diseases. Maxim's research
and development programs are designed to offer hope to patients
by developing safe and effective therapeutic candidates that
have the potential to extend survival while maintaining quality
of life.
Maxim's lead drug candidate Ceplene(TM) (histamine
dihydrochloride), based on the naturally occurring molecule
histamine, is designed to prevent or inhibit oxidative stress,
thereby reversing immune suppression and protecting critical
immune cells. In November 2003, Maxim filed an application
for market authorization in Europe for approval to market
Ceplene for the treatment of advanced malignant melanoma.
Ceplene is currently being tested in Phase 3 cancer clinical
trials for advanced malignant melanoma with liver metastasis
and acute myeloid leukemia. Phase 2 trials of Ceplene are
also underway for the treatment of hepatitis C and advanced
renal cell carcinoma. More than 2,000 patients have participated
in 17 completed and ongoing clinical trials of Ceplene.
In addition to Ceplene, Maxim is developing
small-molecule inhibitors and activators of programmed cell
death, also known as apoptosis, which may serve as drug candidates
for cancer, cardiovascular disease and other degenerative
diseases. The Company's third technology platform, the MX8899
topical gel, is being tested in an attempt to help patients
who suffer from oral mucositis and radiation dermatitis, both
of which are debilitating side effects of certain cancer therapies.
Ceplene, the apoptosis inducers, and MX8899 are investigational
drugs and have not been approved by the U.S. Food and Drug
Administration (FDA) or any international regulatory agency.
This news release contains certain forward-looking
statements that involve risks and uncertainties. Such forward-looking
statements include statements regarding the efficacy, safety
and intended utilization of Ceplene, the oral histamine formulation,
the apoptosis inducers, and MX8899, and the conduct, results
and timelines associated with the Company's clinical trials.
Such statements are only predictions and the Company's actual
results may differ materially from those anticipated in these
forward-looking statements. Factors that may cause such differences
include the risk that products that appeared promising in
early research and clinical trials do not demonstrate safety
or efficacy in larger-scale clinical trials, the risks associated
with dependence upon key personnel, and the risk that the
Company will not obtain approval to market its products. These
factors and others are more fully discussed in the Company's
periodic reports and other filings with the Securities and
Exchange Commission.
Note:The Maxim logo is a trademark
of the Company.
Editor's Note: This release is also available on the Internet
at http://www.maxim.com.
CONTACT: Maxim Pharmaceuticals, San Diego
Larry G. Stambaugh or Anthony E. Altig, 858-453-4040
or
Burns McClellan
Aline Schimmel, 212-213-0006
or
CCG Investor Relations
Sean Collins or Valerie Bent, 818-789-0100
Back to top
Roche Reports
on Two Major Achievements in Japan, the World's Second Largest
Pharmaceuticals Market
Chugai and Roche sign licensing agreement
for anti-cancer drugs Avastin and Omnitarg in Japan - Pegasys
reimbursement achieved and launched in Japan
BASEL, Switzerland, Dec. 15, 2003 - Roche
and Chugai Pharmaceutical Co., Ltd., Tokyo, Japan, (“Chugai”)
announced today two major achievements that will further strengthen
the Roche Group’s position in the important Japanese
market – a new licensing agreement for two innovative
cancer drugs and the launch of Pegasys for hepatitis C.
Licencing Agreement for Cancer
Drugs
Roche and Chugai have signed a licensing agreement under which
Chugai will obtain exclusive rights in Japan to develop and
market two innovative anti-cancer drugs, Avastin (bevacizumab),
and Omnitarg (pertuzumab), both discovered by Genentech, USA.
Chugai will pay license fees to Roche for the two drugs. Roche
holds the exclusive rights outside the US and Genentech in
the US.
“There are approximately 1.3 million
people in Japan who suffer from various cancers , hence the
huge need for new and better medicines. We believe that Avastin
and Omnitarg represent an important step forward in the fight
to treat cancer” said William M Burns, Head of Roche’s
Pharmaceutical Division. “The addition of these two
drugs to Chugai’s portfolio will also further strengthen
our position in Japan, the world’s second largest pharmaceuticals
market.”
About Avastin
Avastin – a recombinant humanized therapeutic antibody
- inhibits Vascular Endothelial Growth Factor (VEGF), a protein
that is believed to play an important role in tumor angiogenesis.
By inhibiting VEGF, Avastin interferes with the blood supply
to tumors, thereby inhibiting tumor growth and potentially
leading to tumor regression. It represents a promising, novel
anti-cancer approach with a broad potential in a number of
solid tumors, and is likely to be complementary with current
chemotherapy approaches.
Chugai plans to start phase I clinical
trials for Avastin next year with an initial target indication
of metastatic colorectal cancer. Avastin has been filed by
Roche in Europe and Genentech in the United States, both submissions
for colon cancer. It is also being evaluated as a potential
therapy in lung, renal, and other cancers. Genentech and Roche
are either planning for, or currently conducting clinical
trials for indications other than colon cancer, and depending
on the outcome, Chugai will seek for additional indications
in Japan.
About Omnitarg
Omnitarg is a recombinant humanized monoclonal antibody which
blocks the ability of human epidermal growth factor type 2
(HER2) receptor to partner with other HER receptor group members
(HER1/EGFR, HER3, and HER4). As a result, cell signaling within
cancer cells is blocked, which ultimately leads to cancer
cell growth inhibition regardless of the HER2 expression.
Chugai plans to start phase I clinical trials for Omnitarg
next year for the target indications of non-small cell lung
cancer, breast cancer, prostate cancer and ovarian cancer.
Omnitarg is currently under joint development by Genentech
and Roche in the United States and Europe. In the United States,
its safety has been confirmed in the phase I clinical trials
and its efficacy has been shown in the patients studied. The
phase II clinical trials have commenced for breast, non-small-cell
lung, prostate, and ovarian cancers with low HER2 expression.
Product Launch and NHI Drug Price Listing of Pegasys
in Japan
Chugai announced that it had launched Pegasys for the treatment
of chronic hepatitis C infection, following its listing on
the National Health Insurance (NHI) drug reimbursement price
list. Pegasys was approved in Japan on October 16, 2003 under
the fast track review process and was launched on December
12th 2003 just after a year from its filing.
In Japan about 400,000 to 500,000 people
with hepatitis C infection have been on therapy and there
are between 30,000 and 40,000 patients each year who receive
interferon treatments for chronic hepatitis C infection. In
addition to these numbers it is estimated that there are 1.5
million carriers of the hepatitis C virus. Pegasys is Japan’s
first approved pegylated interferon and patients now have
the option to choose an efficacious hepatitis C treatment
with a more convenient once-weekly dosage.
Pegasys was developed by Roche and was
approved in Switzerland in July 2001. Since then, it has been
approved as a treatment for chronic hepatitis C in 86 counties
including the EU and United States. In these countries, Pegasys
has already gained significant market share (over 50% of new
prescriptions in the US) due to its higher cure rates compared
to conventional interferon therapy.
About Roche
Headquartered in Basel, Switzerland, Roche
is one of the world’s leading innovation-driven healthcare
groups. Its core businesses are pharmaceuticals and diagnostics.
Roche is number one in the global diagnostics market, the
leading supplier of pharmaceuticals for cancer and a leader
in virology and transplantation. As a supplier of products
and services for the prevention, diagnosis and treatment of
disease, the Group contributes on a broad range of fronts
to improving people’s health and quality of life. Roche
employs roughly 65,000 people in 150 countries. The Group
has alliances and R&D agreements with numerous partners,
including majority ownership interests in Genentech and Chugai.
About Chugai
Chugai Pharmaceutical Co., Ltd. is one
of Japan’s leading research-based pharmaceutical companies
with strengths in biotechnology products and in the therapeutic
fields of oncology, renal diseases, cardiovascular diseases,
bone/joint diseases and transplantation/infection/immunity.
With pharmaceutical sales of 237 billion yen in 2002, Chugai
has invested in research and development capabilities in the
US and Europe, and has established sales and marketing operations
in France, Germany and the UK. Chugai employs 5,774 employees
world-wide.
Chugai has continued to contribute to the
medical community by drawing on its strengths in oncology,
which is one of its strategic therapeutic field, through its
long-standing experience in the development and marketing
of anti-cancer drugs such as Xeloda, Herceptin, Furtulon and
Rituxan in addition to supportive treatments such as the G-CSF,
Neutrogin and anti-emetic drug, Kytril. By adding the novel
antibody drugs Avastin and Omnitarg to its anti-cancer product
portfolio, Chugai’s strengths in the oncology field
are further enhanced, and will greatly contribute to the field
of cancer treatment.
These licensing events of the two drugs
is the successful result of the collaboration between Chugai,
Roche, and Genentech and Chugai will continue to contribute
to the unmet needs of the medical community by creating innovative
new drugs by uniting the research and development resources
of the three companies.
About Genentech
Genentech is a leading biotechnology company
that discovers, develops, manufactures and commercializes
biotherapeutics for significant unmet medical needs. Sixteen
of the currently approved biotechnology products originated
from or are based on Genentech science. Genentech manufactures
and commercializes 11 biotechnology products in the United
States. The company has headquarters in South San Francisco,
California and is traded on the New York Stock Exchange under
the symbol DNA. For additional information about the company,
please visit the Internet.
Contact:
F. Hoffmann-La Roche Ltd
Group Headquarters
Grenzacherstrasse 124
CH-4070 Basel
Switzerland
Telephone +41-61-688 1111
Telefax +41-61-691 9391
Email Corporate Webmaster
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December 16th, 2003
InterMune
Announces Presentation of Interim Findings of the First Clinical
Experience of Infergen Plus Actimmune Combination Therapy
in Hepatitis C Nonresponders
BRISBANE, Calif., Dec. 16 /PRNewswire-FirstCall/
-- InterMune, Inc. (Nasdaq: ITMN) announced today the presentation
of interim findings from an independent retrospective clinical
analysis done in collaboration with the New Jersey Medical
Liver Center evaluating the clinical use of Infergen(R) (interferon
alfacon-1) plus Actimmune(R) (interferon gamma-1b) in combination
for the treatment of chronic Hepatitis C nonresponders. The
clinical analysis was presented today at the 5th biennial
HepDART meeting.
The results presented were a summary of
a retrospective analysis conducted on 32 patients who had
previously failed to show any significant reduction in viral
load following 12 weeks of therapy with peg IFN-alpha 2 plus
ribavirin. This subpopulation of nonresponders is typically
referred to as nullresponders and is considered to be one
of the most difficult patient populations to treat. During
the course of their clinical care, these nonresponders are
being administered Infergen daily (15 micrograms), and Actimmune
three times weekly (50 micrograms), for 48 weeks; ribavirin
is not part of the regimen. The use of these compounds in
combination is not approved by the FDA.
After 12 weeks of therapy with Infergen and Actimmune, 38%
of this nonresponder patient group had undetectable levels
of virus in their blood. Further, 65% of the patients had
at least a 2 log decline in viral load. No patients discontinued
therapy. Five patients received growth factor therapy for
reductions in absolute neutrophil counts, a recognized side
effect of interferon therapy. Other side effects observed
were consistent with Infergen and Actimmune therapy. While
these data are encouraging, important data points on sustained
virologic response have not yet been collected.
"Treatment options for peg IFN-alpha
2 plus ribavirin nonresponders are very limited," said
Carroll Leevy M.D., Director of Clinical Affairs, The New
Jersey Medical Liver Center and Sammy Davis Jr. National Liver
Center, Newark, New Jersey. "The data from this patient
experience are encouraging, and this combination therapy may
offer hope to patients who do not respond to standard interferon
plus ribavirin therapy."
The scientific rationale for use of combination
therapy of interferon alfacon plus interferon gamma is based
on a number of observations. Scientific publications state
that clearance of acute HCV infection requires a potent interferon
gamma response. In addition, clearance of HCV in chronic patients
treated with interferon-alpha requires activity that is mediated
by interferon gamma. In InterMune labs, scientists analyzed
the direct antiviral effects of Infergen and Actimmune in
in vitro models. These models demonstrated very strong synergistic
effects for a range of varying doses of combination therapy
relative to Infergen monotherapy. Analysis of gene expression
showed that several genes that undertake critical cellular
processes were not significantly upregulated by either drug
alone, but were upregulated by the combination of Infergen
and Actimmune.
"These preliminary clinical findings
are consistent with our demonstration of antiviral synergy
upon co-administration of Infergen and Actimmune in in vitro
models as presented at the American Association for the Study
of Liver Disease Conference in October," said James E.
Pennington, M.D., Executive Vice President of Medical and
Scientific Affairs at InterMune. "While we await analysis
of sustained virologic response, we are considering the initiation
of an InterMune-sponsored clinical program using the combination
of our two interferon products, Infergen and Actimmune, for
the treatment of chronic Hepatitis C."
About Chronic Hepatitis C
According to the Centers for Disease Control an estimated
3.9 million (1.8%) Americans have been infected with HCV,
of whom 2.7 million are chronically infected. Hepatitis C
causes an estimated 10,000 to 12,000 deaths annually in the
United States. The prevalence of chronic hepatitis C is increasing.
About Infergen(R) (interferon alfacon-1)
Infergen is a bio-optimized type 1 interferon alpha indicated
for treatment of adult patients with chronic HCV infections
and is dosed three times a week. Infergen is the only interferon
alpha with data in the label regarding use in patients following
relapse or non-response to treatment with certain previous
treatments. The most common side effects are flu-like symptoms
(i.e. headache, fatigue, fever, myalgia, and rigors). Physicians
and patients can obtain additional prescribing information
regarding Infergen, including the product's safety profile,
by visiting www.infergen.com, including the black box warning
for all interferon alphas regarding psychiatric, autoimmune,
ischemic and infectious disorders.
About Actimmune(R) (interferon gamma-1b)
Interferon gamma is a naturally occurring protein that stimulates
the immune system. InterMune markets Actimmune for the treatment
of two life-threatening congenital diseases: chronic granulomatous
disease and severe, malignant osteopetrosis. The most commons
side effects are flu-like symptoms, including fever, headache
and chills. InterMune is also conducting a Phase III study
of interferon gamma-1b in idiopathic pulmonary fibrosis, a
Phase III study of interferon gamma-1b in ovarian cancer and
a Phase II study of interferon gamma-1b in severe liver fibrosis,
or cirrhosis, caused by hepatitis C virus (HCV). Physicians
and patients can obtain additional prescribing information
regarding Actimmune, including the product's safety profile,
by visiting www.actimmune.com.
About InterMune
InterMune is a biopharmaceutical company
focused on the applied research, development and marketing
of life-saving therapies for pulmonary and hepatic disease.
For additional information about InterMune, please visit www.intermune.com.
Except for the historical information contained
herein, this press release contains certain forward-looking
statements by InterMune that involve risks and uncertainties,
including without limitation the statements indicating that
the data for the use of Infergen and Actimmune in combination
are encouraging compared to current treatment options and
that this combination therapy may offer hope to patients who
do not respond to standard interferon plus ribavirin therapy.
All forward-looking statements and other information included
in this press release are based on information available to
InterMune as of the date hereof, and InterMune assumes no
obligation to update any such forward-looking statements or
information. InterMune's actual results could differ materially
from those described in InterMune's forward-looking statements.
Factors that could cause or contribute to such differences
include, but are not limited to those discussed under the
heading "Risk Factors" and the risks and factors
discussed in InterMune's 10-Q report filed with the SEC on
November 13, 2003, and other periodic reports (i.e., 10-K
and 8-K) filed with the SEC. The risks and other factors that
follow, concerning the forward-looking statements in this
press release, should be considered only in connection with
the fully discussed risks and other factors discussed in detail
in the 10-Q report and InterMune's other periodic reports
filed with the SEC. InterMune's forward-looking statements
in this press release concerning the use of Infergen and Actimmune
for the treatment of Hepatitis C are subject to the risks
and uncertainties that include, without limitation, those
associated with obtaining statistically significant data from
clinical trials; the uncertain, lengthy; and expensive drug
research and development and regulatory process; competition;
budget constraints and InterMune's ability to obtain, maintain
and enforce patents and other intellectual property.
SOURCE InterMune, Inc.
CONTACT:
For Investors
Myesha Edwards of InterMune, Inc.
415-466-2242
or ir@intermune.com
or media
Ian McConnell of WeissCom Partners, Inc.
415-362-5018
or ian@weisscom.net, for InterMune, Inc.
http://www.intermune.com
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XTLbio R&D
and Business Development Update
Rehovot, Israel, 16 December 2003 - XTL
Biopharmaceuticals Ltd (XTLbio) today announces an update
on recent clinical progress and corporate developments to
investors and analysts.
Highlights
Phase 2 trial initiated with HepeX™-B in hepatitis B
patients for the prevention of infection following liver transplant
Interim clinical results for HepeX™-C dose escalation
trial Progress in discussions on HepeX™ corporate alliances
HepeX™-B Update: dosing commenced
in Phase 2b trial XTLbio has commenced dosing in a Phase 2b
trial with HepeX-B for the prevention of re-infection in hepatitis
B patients following liver transplant.
The trial is being conducted in the US,
Europe and Israel and involves 45 patients. Patients receiving
the current first-line preventative treatment, blood derived
polyclonal hepatitis B immune globulin (HBIg) solution together
with lamivudine, will be randomised to three cohorts; one
cohort continuing on the standard preventative treatment and
two cohorts receiving different doses of HepeX-B together
with lamivudine. The goal of the study is to demonstrate that
replacement of HBIg with HepeX-B in the current prophylaxis
protocol in HBV liver transplant patients is effective in
preventing HBV re-infection. Patients will be treated over
a six-month period, with a 12-month follow-on observation
period. Primary endpoints will be HBV DNA and HBV antigen
levels. Secondary endpoints will be anti-HBV antibody blood
levels and the safety of HepeX-B compared to the current drug.
HepeX-B is a combination of two fully human
monoclonal antibodies acting on the hepatitis B virus surface
antigen, which were selected based on their strong activity
against the virus in XTLbio's pre-clinical Trimera™
model. In a recently reported study, HepeX-B maintained serum
levels similar to or higher than the current first-line treatment
(HBIg), while using 1,000 times less drug. In August this
year, HepeX-B was granted Orphan Drug Designation from the
US Food and Drug Administration, giving the product exclusive
marketing rights in the US for seven years following marketing
approval.
Dr Neil Graham, Chief Medical Officer of
XTLbio, said: "Chronic hepatitis B is the most common
serious liver infection in the world and can be fatal for
patients whose disease progression necessitates a liver transplant.
In the phase 2 trial announced today, we hope to be able to
confirm the beneficial effects of HepeX-B seen in earlier
studies and show a meaningful benefit to patients who have
undergone liver transplant.
"HepeX™-C Update: Interim clinical results from
dose escalation trial
XTLbio discloses preliminary clinical results from its Phase
2a randomised placebo controlled dose-escalation / safety
study on HepeX-C. The interim results involved 12 HCV associated
liver transplant patients who received the low dose regimens
of HepeX-C for three months after their transplants.
Based on the absence of drug related severe
adverse events on these initial twelve patients together with
amendments to include additional cohorts, the FDA has permitted
the higher dosing regimen. XTLbio is now proceeding with completing
the higher dose cohorts in the 24 patient study.
HepeX-C is a fully human high-affinity
monoclonal antibody, which was shown to reduce viral levels
of the HCV virus in chronic HCV patients in a Phase 1b dose
ranging safety study. Based upon safety data generated in
that study, XTLbio decided to clinically evaluate HepeX-C
in liver transplant patients infected with HCV. The study
is aimed at achieving the minimum dose necessary of HepeX-C
to bind all free HCV virus in the blood stream and thereby
prevent or delay re-infection of the transplanted liver with
HCV, known as “antibody excess”. It is believed
antibody excess could potentially prevent or significantly
delay re-infection of patients with HCV after their transplant.
The continuation of the dose escalation study in 12 additional
patients is designed to find the minimum dose necessary to
achieve antibody excess while demonstrating safety.
Dr. Shlomo Dagan, XTLbio’s Chief
Scientific Officer, stated: “As reported at the recent
AASLD liver meeting in Boston, one of the most critical needs
for liver transplant specialists today is to find an approach
to limit the devastating effects of HCV re-infection. The
prognosis for such patients begs for a solution. Our strategy
to achieve antibody excess is fully justified based upon our
review of the data. Therefore we look forward to completing
this trial in HepeX-C in transplant recipients.”
Business Development Update
XTLbio is making progress to secure an alliance on our HepeX
programs. Securing a partner for one or more of our products
remains the key priority for XTLbio. Glenn Kazo, Chief Business
Officer of XTLbio, said: “We are encouraged by the high
level of interest shown in our pipeline and are in discussions
of various stages with a number of potential partners. It
is our intention to conclude a value enhancing partnership
at the earliest possible opportunity and we are working continuously
to achieve this."
XTL CONTACTS
Martin Becker, PhD
President & CEO
+972-8-930-4440
Glenn Kazo
CBO
+1-603-878-9857
Financial Dynamics
David Yates, Sarah MacLeod
+44 (0) 20 7831 3113
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Dec 17th , 2003
ViroLogic
Presents Data Using New Hepatitis C Virus Drug Resistance
Assay
KAUAI, Hawaii, Dec. 17 /PRNewswire-FirstCall/
-- ViroLogic, Inc. (NASDAQ:VLGC) announced today a presentation
on the Company's development of a novel Hepatitis C virus
(HCV) drug susceptibility assay with applications in drug
discovery and development. The findings were presented by
Neil Parkin, Ph.D., Scientific Director of Research at ViroLogic,
at the 5th biennial HepDART meeting "Frontiers in Drug
Development for Viral Hepatitis" held in Kauai, Hawaii,
December 14-18.
"Recent research advances have boosted
understanding of Hepatitis C virus replication and provided
the biopharmaceutical industry with several new targets for
potential therapeutic intervention," said Bill Young,
ViroLogic's Chairman and Chief Executive Officer. "The
HepDART presentation illustrates how ViroLogic's expertise
in virology and assay development can be applied to facilitate
the development of therapeutics for the treatment of this
serious chronic disease."
The study entitled, "Sequence Analysis
of NS5B in Genotype 1 HCV: Extensive Sequence Variability
and Naturally Occurring Polymorphisms Which May Affect Polymerase
Inhibitor Activity" characterized the natural genetic
variation in HCV polymerase (NS5B) using ViroLogic's newly
developed genotyping assay. The assay is currently available
to biopharmaceutical companies for generation of clinical
data for evaluation of a promising new class of anti-HCV drugs
that target the viral polymerase.
Dr. Parkin also described the Company's
ongoing effort to assemble a large database of complete genotype
1 NS5B sequences, which has already uncovered significant
diversity. By mapping the regions of genetic variability to
the structure of the polymerase, drug developers may be able
to target areas of least variation for drug development and
predict potential baseline variability in viral susceptibility
to candidate anti-HCV drugs. ViroLogic is also developing
a phenotypic assay to assess the effect this natural variation
has on drug susceptibility.
About Hepatitis C
Hepatitis C is one of the most common chronic blood-borne
infections in the United States. According to the U.S. Centers
for Disease Control and Prevention, approximately 3.9 million
Americans are infected with HCV. Currently, no vaccine is
available to prevent new HCV infections. Left untreated, chronic
HCV infection often leads to end stage liver disease and is
the leading reason for liver transplantation in the United
States. In contrast to the current treatment of chronic HCV
infection, a combination of interferon and ribavirin, the
next generations of anti-HCV drugs are designed to target
specific viral proteins and directly block critical steps
in the HCV replication cycle.
About ViroLogic
ViroLogic is a biotechnology company advancing individualized
medicine by discovering, developing and marketing innovative
products to guide and improve treatment of serious viral diseases
such as AIDS and hepatitis. The company's products are designed
to help doctors optimize treatment regimens that lead to better
patient outcomes and reduced costs. ViroLogic's technology
is also being used by numerous biopharmaceutical companies
to develop new and improved anti-viral therapeutics and vaccines
targeted at emerging drug-resistant viruses. More information
about the Company and its technology can be found on its web
site at www.virologic.com.
Certain statements in this press release
are forward-looking. These forward-looking statements are
subject to risks and uncertainties and other factors, which
may cause actual results to differ materially from the anticipated
results or other expectations expressed in such forward-looking
statements. These risks and uncertainties include, but are
not limited to, the risk that the Company's products for patient
testing may not continue to be accepted or that increased
demand from physicians or from drug development partners may
not develop as anticipated, the risk that ViroLogic may not
continue to realize anticipated benefits from its cost-cutting
measures, the timing of pharmaceutical company clinical trials,
whether payors will authorize reimbursement for its products,
whether the FDA or any other agency will decide to regulate
ViroLogic's products or services, whether the Company will
encounter problems or delays in automating its processes,
whether ViroLogic successfully introduces new products, whether
others introduce competitive products, whether intellectual
property underlying the Company's technology is adequate,
whether licenses to third party technology will be available,
whether ViroLogic is able to build brand loyalty and expand
revenues, and whether ViroLogic will be able to raise sufficient
capital when required. For a discussion of other factors that
may cause ViroLogic's actual events to differ from those projected,
please refer to the Company's most recent annual report on
Form 10-K and quarterly reports on Form 10-Q, as well as other
subsequent filings with the Securities and Exchange Commission.
Web site: http://www.virologic.com
Source: ViroLogic, Inc.
CONTACT: Karen Wilson, CFO of ViroLogic, Inc., +1-650-624-4164,
or
kwilson@virologic.com
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December 18, 2003
Chiron Grants
Nonexclusive HCV License To Boehringer Ingelheim
PR Newswire
EMERYVILLE, Calif., Dec. 18 /PRNewswire-FirstCall/
-- Chiron Corporation (Nasdaq: CHIR) today announced that
it has granted to Boehringer Ingelheim International GmbH
a nonexclusive license for the research, development and commercialization
of small molecule therapeutics against hepatitis C virus (HCV)
drug targets. Under the terms of the agreement, Boehringer
Ingelheim would pay Chiron up-front license fees, milestone
payments and royalties on products. The specific financial
terms and other details of the license were not disclosed.
"This agreement is a further example
of Chiron's strong commitment to making its technology widely
available to companies working to find therapies for hepatitis
C," said William G. Green, Esq., Chiron general counsel.
"We continue to strategically leverage our HCV intellectual
property and actively license this technology to other companies,
while we pursue our own research into therapeutic agents for
hepatitis C."
About Hepatitis C
In 1987, Chiron scientists Michael Houghton, Ph.D.; Qui-Lim
Choo, Ph.D.; and George Kuo, Ph.D., cloned and first identified
HCV as the cause of transfusion-related non-A, non-B hepatitis.
This breakthrough marked the first time a virus was cloned
before it had been grown in tissue culture or otherwise isolated.
The Chiron scientists received the prestigious Lasker Award
in recognition of this discovery. Since the initial work,
Chiron has been granted more than 100 HCV-related patents
in over 20 countries, including patents directed to hepatitis
C polypeptides encoded throughout the genomes of HCV. Such
polypeptides can be used in a variety of medical applications,
including blood screening, clinical diagnosis, vaccines and
as therapeutic targets for drug screening. A number of therapeutic
companies have been granted nonexclusive licenses to Chiron's
HCV technology for drug screening purposes, including Bristol-Myers
Squibb, GlaxoSmithKline, Japan Tobacco Inc., Gilead and Pfizer.
About Chiron Chiron Corporation
Headquartered in Emeryville, California,
is a global pharmaceutical company that leverages a diverse
business model to develop and commercialize high-value products
that make a difference in people's lives. The company has
a strategic focus on cancer and infectious disease. Chiron
applies its advanced understanding of the biology of cancer
and infectious disease to develop products from its platforms
in proteins, small molecules and vaccines. The company commercializes
its products through three business units: BioPharmaceuticals,
Vaccines and Blood Testing. For more information about Chiron,
visit the company's website at www.chiron.com.
This news release contains forward-looking
statements regarding royalty revenue and the possible grant
of additional licenses that involve risks and uncertainties
and are subject to change. A full discussion of the company's
operations and financial condition, including factors that
may affect its business and future prospects, is contained
in documents the company has filed with the SEC, including
the form 10-Q for the quarter ended September 30, 2003, and
the form 10-K for the year ended December 31, 2002, and will
be contained in all subsequent periodic filings made with
the SEC.
Consistent with SEC Regulation FD, we do not undertake an
obligation to update the forward-looking information we are
giving today.
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December 19, 2003
Drug Makers Target Hepatitis C Market
Linda A. Johnson, Associated Press
TRENTON, N.J. (AP) Eighteen months before
Hoffmann-La Roche Inc. launched its advanced hepatitis C drug
Pegasys, the drug company began reaching out to physicians
who treat the tough-to-cure virus.
That strategy helped the company grab half
the market in barely a year from Schering-Plough Corp. of
Kenilworth, which had nearly a two-year lead with its Peg-Intron.
Both drugs are long-acting interferons patients inject just
under their skin. They stimulate the immune system to better
fight off the hepatitis virus, which silently destroys the
liver over many years.
“We knew we were playing catch-up,”
said George Abercrombie, chief executive officer of Nutley,
N.J.-based Hoffmann-La Roche, the U.S. pharmaceutical subsidiary
of Switzerland's Roche Group.
“This company was focused like a
laser around the launch of Pegasys” in October 2002,
Abercrombie told The Associated Press.
Besides hiring more sales representatives
focused on the 15,000 U.S. doctors specializing in hepatitis
treatment, the company gave 12-week supplies of Pegasys free
to about 12,000 patients. It also offered wholesalers a 43
percent discount on Copegus, its brand of ribavirin, an antiviral
pill taken with the interferon to boost its effectiveness.
Copegus and Schering-Plough's ribavirin,
Rebetol, are swallowed once or twice daily, while Pegasys
and Peg-Intron are injected weekly.
Liz Coyle of health information company
IMS Health said Thursday that Pegasys sales grew quickly and,
as of November, Pegasys had captured 50 percent of the market
from Peg-Intron, with about 19,000 prescriptions dispensed
for each. That's a tiny fraction, though, of the estimated
4 million Americans infected with hepatitis C most of whom
aren't being treated because they don't know they're infected
or can't afford the roughly $25,000 for a course of treatment.
Still, Abercrombie expects Pegasys sales
to peak at $1 billion.
``It's a big surprise to some extent that
Schering, which literally owned the U.S. market, has now given
up the market,'' said independent pharmaceuticals analyst
Hemant Shah of HKS & Co. in Warren. ``Somebody dropped
the ball and now they're paying for it.''
Spokesman Bob Consalvo concedes Schering-Plough
erred in cutting its sales force 10 percent last year. The
company was struggling with a dramatic drop in sales for its
longtime blockbuster allergy drug Claritin, now sold over
the counter, and other major problems.
Now under a new CEO, turnaround whiz Fred
Hassan, Schering-Plough is fighting to win back revenues for
what is now the company's biggest franchise.
Consalvo said Schering-Plough is restoring
its sales force to the original size and offering its own
discounts. Early next year, it will launch a pen-like injection
device called Redipen that with a click mixes Peg-Intron with
liquid stored separately inside easier for patients than mixing
the two in a vial and drawing it into a syringe.
Schering-Plough's drug comes in four doses
according to patients' weight, which it argues increases effectiveness.
Hoffmann-La Roche disputes that.
Schering-Plough next month will begin the
first head-to-head experiments comparing Peg-Intron and Pegasys,
but results won't be available for a couple years.
"They seem to be generally equal in
efficacy ... in combination with ribavirin,'' said Dr. Gary
Simpson, medical director for infectious diseases at the New
Mexico Department of Health.
Both cure about 50 percent of patients
with the toughest hepatitis subtype to treat, and about 80
percent of those with two less-resistant types. That's a huge
improvement over a decade ago, when the companies' drugs cured
only 10 percent to 15 percent of patients.
Many patients have trouble enduring those
effects flu-like symptoms, extreme anemia and fatigue, depression
and lack of appetite over the minimum 48-week treatment.
Some patients say Pegasys is easier to
bear.
"It didn't knock me down, and I didn't lose all the weight
I did on Peg-Intron,'' said Monte Glosson, a 50-year-old Dripping
Springs, Texas, gas station and towing service owner who said
he got much sicker over 10 months of treatment with Peg-Intron
and was nearly incapacitated. In January his doctor put him
on Pegasys.
“After two months I was clear”
of the virus, Glosson said.
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