
HCV
Advocate easl 2007 News Review
Week Ending:
In This Issue:
Hepatitis C
·
Firm's Future Hinges
on New Hepatitis Drug
·
Bullish Views on Vertex
ahead of Liver Meeting
·
Analysis: Total
Hepatitis C Cure Possible
·
Idenix Midstage
Study Results Mixed
·
Viropharma:
Hepatitis-C Treatment More Effective in Combination
·
Higher Doses of Ribavirin
Are Effective in Hepatitis C Virus Genotype 1 Patients: Presented at EASL
Hepatitis B
·
ANA380 Exhibits Activity In Vitro
Against Multiple Clinically Relevant Hepatitis B Virus Mutants
Download PDF version of
this News Review:
April 9th, 2007
By Stephen Heuser, Globe Staff
For one of Boston's biggest
biotechnology companies, the future hinges on a potential billion-dollar drug
and a liver-research conference about to kick off 3,700 miles away in Spain.
At the annual meeting of the
European Association for the Study of the Liver , starting this week in
Barcelona, perhaps the most hotly anticipated presentation will be Vertex
Pharmaceuticals Inc.'s unveiling of new data from human trials of its pill for
hepatitis C.
Between 3 million and 4
million Americans are thought to be infected with hepatitis C, a virus that can
lead to cancer and liver failure. It spread through the blood supply before
broad screening began in the early 1990s. Infected people can harbor the
disease without symptoms for over a decade.
Vertex's pill, which mounts a
new type of attack on the virus, has achieved dramatic results in early tests on
a handful of infected patients. In most, it appeared to eradicate the virus in
a matter of weeks. On Saturday evening the company plans to unveil details of a
bigger trial on 250 patients, comparing those on standard therapy with others
who got therapy plus Vertex's drug.
Dr. Raymond Chung , a liver
specialist at Massachusetts General Hospital , said Saturday's results won't
tell the whole story, but he called them an important indicator of how well the
drug might work. Along with a handful of similar drugs in development, he said,
"You're seeing the leading edge of a real shift in treatment."
Currently, patients are
prescribed a year's worth of interferon injections plus pills, an $18,000
course of therapy that causes symptoms like a severe flu, and cures half of
those who endure it.
Chung said he was particularly
interested in one "shoot-the-moon" strategy that Vertex was
employing. In a multipart trial of the drug, one group was taken off treatment
after just three months -- far less time than the current standard of a year.
On Saturday, Vertex expects to reveal whether the virus bounced back in those
short-term patients, or whether they managed to stay virus-free long enough to
be considered cured.
Even if Vertex's pill can't
eradicate the virus in 12 weeks, Chung said, it could still be important if it
boosts longer-term interferon treatment.
In a reflection of how crucial
the drug is for the company, Vertex's stock has risen and fallen sharply in the
past year with disclosures of even tiny pieces of medical data. It jumped
nearly 20 percent one day last fall when some early positive news came out on a
trial; it slid in December when the company revealed that 9 percent of
clinical-trial patients had to discontinue treatment because of a serious rash
and other side effects. Last week, the stock rose 10 percent, simply on
anticipation that this weekend's results would be positive.
With 700 local employees and
an 18-year history in Cambridge, Vertex is a pillar of the local biotechnology
landscape. But its ups and downs suggest how important a single disease, and a
single product, can be to even a well-established biotech company.
Vertex has only one product on
the market, a minor AIDS drug sold by GlaxoSmithKline PLC. The company loses
money every year, paying far more for research than it books in revenue, but
one big success could change that equation. Although its hepatitis C drug is
unlikely to reach the market before 2009, analysts estimate it could rack up
sales of $1 billion a year.
Attracted by that potential
market, a number of other firms are taking aim at hepatitis C, many in Boston.
Enanta Pharmaceuticals Inc. , a private company in Watertown, recently signed a
deal with Abbott Laboratories of Illinois to develop drugs similar to the one Vertex
is testing.
Idenix Pharmaceuticals Inc.,
which is majority-owned by Swiss drug giant Novartis AG, is testing a drug with
a slightly different mechanism, as is the New Haven company Achillion
Pharmaceuticals Inc.
The promise of a fast-acting
new treatment for hepatitis C has already paid off for Vertex, which signed an
international sales deal with Johnson & Johnson last summer. But it also
carries risks. A hepatitis C drug being developed by a European company caused
toxic side effects in animals. And after unsuccessful trials, Coley
Pharmaceutical Group of Wellesley suspended tests of its experimental hepatitis
C drug in January, laying off 33 of its 150 employees.
This week's presentation is
only the first in a series of findings expected from Vertex. Still in the
wings: a larger trial involving 320 patients, and a third trial with 440
patients who weren't cured by standard therapy.
If the company succeeds, it
will also face another question: What to do about the tens of millions of
people with hepatitis C in developing nations who can't afford the steep price
of therapy.
Vertex said it has a deal with
Johnson & Johnson to start an international foundation dedicated to
hepatitis C treatment.
"It's something that we've
talked about extensively, and having a partner that shared our view of the
importance of that was key," said Vertex spokesman Michael Partridge ,
although he said it was too early to discuss details of the program.
Stephen Heuser can be reached
at sheuser@globe.com.
April 10th,
2007
By Bill Berkrot - Analysis
NEW YORK (Reuters) - Vertex
Pharmaceuticals Inc. (VRTX.O: Quote, Profile, Research) will present data on
its closely watched experimental hepatitis C treatment this week and many
analysts are saying this is a good time to buy the company's beaten down shares
despite the risk that the data could disappoint.
Investors appear to be
listening, as Vertex shares have recovered about 14 percent in recent days
ahead of the European liver disease meeting in Barcelona at which the data will
be unveiled on Saturday.
The shares had shed about a
third of their value from late November through March as enthusiasm for the
drug, VX-950 or telaprevir, was tempered by safety concerns.
The shares broke back through
the $30 barrier late last week and climbed another 2 percent on Tuesday to
$32.16 after trading at around $45 back in November.
Sanford Bernstein analyst
Geoffrey Porges thinks the data coming out of the meeting will calm investor
nerves substantially and is encouraging clients to buy Vertex shares.
"I believe that we'll
come away from this meeting believing that VX-950 is still the leading and most
likely candidate to transform the treatment of hepatitis C virus," Porges
said.
"We'll see a lot of
preclinical data about other compounds and other combinations of compounds (at
the meeting) but I don't think we'll see anything that is anywhere near where
Vertex is in terms of having significant clinical data," added Porges, who
has a price target of $52 on Vertex shares.
Merrill Lynch analyst Hari
Sambasivam wrote in a research note last month: "While we cannot rule out
further declines, current levels represent an opportunity for patient
investors."
VX-950 is being tested in
combination with two medicines considered to be the gold standard of treatment
-- a long-acting interferon and the antiviral drug ribavirin.
Analysts, investors and liver
specialists will pore over the mid-stage clinical trial data with particular
interest in the sustained virologic response (SVR) of the drug -- the percentage
of patients in whom the virus stayed below detectable levels -- and the number
of patients who dropped out due to adverse side effects.
DROPOUT RATE
Concern over the dropout rate
seen in previous data put considerable pressure on the shares and raised
tolerability concerns, although much of the dropout seen earlier was due to a
rash rather than more serious side effects.
"We view the home run
scenario of 75 percent SVR rate for telaprevir for only 12 weeks of therapy as
possible but a long shot," Piper Jaffray analyst Rachel McMinn wrote in a
research note. "We view an SVR rate in the 40 percent to 50 percent range
as more probable."
Cowen and Co. analyst Phil
Nadeau said investors are likely looking for at least a 40 percent sustained
response. "If you see over 40 to 50 percent, people will be happy; less
than 40 and people will be somewhat disappointed," he said.
"If it's very potent,
people might be more tolerant on the side effects," Nadeau noted. "If
it's thought to be less potent, the side effects become more important."
Much of the focus before the
meeting appears to be on three-month follow-up data from a small subset of
about 20 patients who had treatment stopped after just 12 weeks in an effort to
glean further efficacy and tolerability clues, several analysts said.
However, Bernstein's Porges
believes that group to be far too small to draw meaningful conclusions. He
instead will be looking at the full complement of 175 patients that had started
taking the medicine during the Phase IIb trial.
"When you've got nearly
200 patients treated, and probably you'll see no more than 5 to 10 incidents of
side effects including rash, I think that will calm peoples' fears and
anxieties a lot," Porges predicted.
Options and equities analysts
are expecting near-term volatility, but most are predicting a long-term winner
with sales of the drug eventually exceeding $1 billion a year.
Cowen's Nadeau, who is
forecasting global sales for the drug of $1.5 billion by as early as 2010,
agreed that near-term volatility is likely, but he remains bullish on Vertex.
"This drug is a front
runner in the hepatitis C space," Nadeau said, "and no matter what
happens over the weekend there's still many other ways this can become a very
large, very successful product."
(Additional reporting by Doris
Frankel in Chicago)
April 11th,
2007
Highlights key data at the 42nd annual meeting of the European
Association for the Study of the Liver (EASL)
KENILWORTH, N.J., April 11
/PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE: SGP - News)
reaffirms its commitment to advancing the science and treatment of chronic
hepatitis C virus (HCV) infection with several key data presentations at the
European Association for the Study of the Liver (EASL) 42nd annual meeting in
Barcelona, Spain, April 11-15. A total of 38 data presentations highlighting
Schering-Plough hepatitis medications will be presented at EASL 2007.
Among these are several
studies with PEGINTRON® (peginterferon alfa-2b) and REBETOL® (ribavirin)
combination therapy, a current standard of care in the treatment of chronic
hepatitis C, evaluating how results at important treatment milestones can help
physicians make informed treatment decisions.
Schering-Plough also is
exploring novel therapeutic approaches, both through targeted internal research
programs and strategic collaborations. Chief among these efforts is boceprevir
(SCH 503034), Schering-Plough's investigational oral HCV protease inhibitor
currently in Phase II clinical development for treating chronic hepatitis C.
Individual in vitro studies of boceprevir in combination with investigational
oral HCV polymerase inhibitors from Wyeth/ViroPharma and Idenix/Novartis have
been completed and will be presented at EASL.
"Schering-Plough is proud
of its long-term role in introducing innovative treatments to the field of
hepatitis," said Robert J. Spiegel, M.D., chief medical officer and senior
vice president, Schering-Plough Research Institute. "Our vision with
PEGINTRON, our cornerstone HCV therapy, and ongoing work with boceprevir, our
investigational oral HCV protease inhibitor, is to continue to advance the
science and deliver additional treatment options for patients with hepatitis C
infection."
PEGINTRON
Numerous studies with
PEGINTRON will be presented at EASL evaluating patient response to therapy at
certain treatment milestones, an approach that is aimed at individualising
treatment for patients.
Schering-Plough also is
exploring novel therapeutic approaches with PEGINTRON in combination with
investigational antiviral agents to optimize treatment for patients with more difficult-to-treat
forms of the disease, such as those with HCV genotype 1 and nonresponders to
previous therapy.
Boceprevir (SCH 503034)
Schering-Plough is undertaking
a large, fully integrated clinical development program for its oral HCV
protease inhibitor boceprevir (SCH 503034), with the goal of developing new
strategies for improving treatment outcomes for patients with hepatitis C.
As part of this effort,
Schering-Plough has collaborated with Wyeth/ViroPharma and Idenix/Novartis to
conduct separate in vitro studies of boceprevir in combination with their
respective investigational HCV polymerase inhibitors, HCV-796, a non-nucleoside
polymerase inhibitor, and NM107 (the active moiety of NM283, valopicitabine), a
nucleoside polymerase inhibitor. These in vitro experiments suggest that the
combination of boceprevir and either one of these polymerase inhibitors
achieves additive antiviral activity and a complementary resistance profile;
the combination of two agents increases the barrier for developing resistance
to either drug alone.
In addition, Schering-Plough
has initiated the HCV SPRINT-1 study (HCV Serine Protease Inhibitor Therapy-1),
a large Phase II study that is currently enrolling 400 HCV genotype 1,
treatment-naïve patients in sites across the United States, Canada and Europe.
The primary objective of the study is to evaluate the safety and efficacy of
boceprevir 800 mg TID in combination with PEGINTRON and REBETOL in the
treatment-naïve patient population.
Schering-Plough also is
conducting a large Phase II study evaluating the safety and efficacy of
boceprevir 800 mg TID in combination with PEGINTRON and REBETOL in patients
chronically infected with HCV genotype 1 who were nonresponders to previous
peginterferon and ribavirin combination therapy. The study involves
approximately 350 patients at centers in the United States and Europe. All
study participants have completed treatment and are in the follow-up phase.
Sustained virological response data from this study will be available later in
2007, and will help guide future clinical development of boceprevir.
Key Data Presentations at EASL
PEGINTRON
·
Peginterferon Alfa-2b and Ribavirin for 14 or 24 Weeks in Patients with HCV
Genotype 2 or 3 and Rapid Virological Response, The North-C Trial. Dalgard, O.
et al. Oral presentation, Sunday, April 15, at 13:15, General Session 4.
·
A Pegylated Interferon Alfa-2b Dose Reduction in HCV 1B Patients with
Rapid Viral Response Does Not Affect Sustained Virological Response. Napoli, N.
et al. Poster presentation, Thursday, April 12.
·
Comparison of Early Virologic Response Among Patients with Chronic
Hepatitis C Infected with Genotype Non 2/3 Treated with Pegylated Interferon
Alfa-2b and Ribavirin in Dependence with Hepatic Fibrosis Stages. Berak, H. et
al. Poster presentation, Thursday, April 12.
Bocepevir (SCH 503034)
·
Combination of Two Hepatitis C Virus Inhibitors, SCH 503034 (Boceprevir)
and NM107 (the active moiety of NM283, valopicitabine), Provides Enhanced
Anti-Replicon Activity and Suppresses Emergence of Resistant Replicons.
Ralston, R. et al. Late-breaker poster presentation, Thursday, April 12.
·
Favorable Cross-Resistance Profile of Two Novel Hepatitis C Virus
Inhibitors, SCH 503034 (Boceprevir) and HCV-796, and Enhanced Anti-Replicon
Activity Mediated by the Combined Use of Both Compounds. Howe, A.Y. et al.
Poster presentation Thursday, April 12.
·
SCH 503034 (Boceprevir), an Oral HCV Protease Inhibitor, is Well
Tolerated in Patients with Varying Degrees of Hepatic Impairment. Preston,
R.A., et al. Poster presentation Thursday, April 12.
About PEGINTRON and REBETOL Combination Therapy
PEGINTRON is approved in the
United States for use alone or with ribavirin (800 mg/day) for the treatment of
chronic hepatitis C in patients with compensated liver disease who have not
been previously treated with interferon alpha and who are at least 18 years of
age.
Important Safety Information Regarding U.S. Labeling for PEGINTRON and
REBETOL
WARNING
Alpha interferons, including
PEGINTRON, may cause or aggravate fatal or life-threatening neuropsychiatric,
autoimmune, ischemic, and infectious disorders. Patients should be monitored
closely with periodic clinical and laboratory evaluations. Patients with
persistently severe or worsening signs or symptoms of these conditions should
be withdrawn from therapy. In many but not all cases these disorders resolve
after stopping PEGINTRON therapy.
Ribavirin causes hemolytic
anemia. Anemia associated with REBETOL therapy may exacerbate cardiac disease
that has led to fatal and nonfatal myocardial infarctions. Patients with a
history of significant or unstable cardiac disease should not be treated with
REBETOL. It is advised that complete blood counts (CBC) be obtained at baseline
and at weeks 2 and 4 of therapy or more frequently if clinically indicated.
REBETOL and combination
REBETOL/PEGINTRON therapy must not be used by women, or male partners of women,
who are or may become pregnant during therapy and during the 6 months after
stopping therapy. REBETOL and combination REBETOL/PEGINTRON therapy should not
be initiated until a report of a negative pregnancy test has been obtained
immediately prior to initiation of therapy. Women of childbearing potential and
men must use effective contraception (at least two reliable forms) during
treatment and during the 6- month post-treatment follow-up period. Significant
teratogenic and/or embryocidal effects have been demonstrated for ribavirin in
all animal species in which adequate studies have been conducted. These effects
occurred at doses as low as one twentieth of the recommended human dose of
REBETOL. If pregnancy occurs in a patient or partner of a patient during
treatment or during the 6 months after treatment stops, physicians are
encouraged to report such cases by calling (800) 727-7064.
PEGINTRON
There are no new adverse
events specific to PEGINTRON as compared to INTRON® A (Interferon alfa-2b,
recombinant) for Injection; however, the incidence of some (e.g., injection
site reactions, fever, rigors, nausea) were higher. The most common adverse
events associated with PEGINTRON were "flu- like" symptoms, occurring
in approximately 50 percent of patients, which may decrease in severity as
treatment continues. Application site disorders were common (47 percent), but
all were mild (44 percent) or moderate (4 percent) and no patient discontinued,
and included injection site inflammation and reaction (i.e., bruise, itchiness,
irritation). Injection site pain was reported in 2 percent of patients
receiving PEGINTRON. Alopecia (thinning of the hair) is also often associated
with alpha interferons including PEGINTRON.
Psychiatric adverse events,
which include insomnia, were common (57 percent) with PEGINTRON but similar to
INTRON A (58 percent). Depression was most common at 29 percent. Suicidal
behavior including ideation, suicidal attempts, and completed suicides occurred
in 1 percent of patients during or shortly after completing treatment with
PEGINTRON.
PEGINTRON/REBETOL is
contraindicated in patients with autoimmune hepatitis, decompensated liver
disease, and in patients with hemoglobinopathies (e.g., thalassemia major,
sickle-cell anemia).
The following serious or
clinically significant adverse events have been reported at a frequency less
than 1 percent with PEGINTRON or interferon alpha: severe decreases in
neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension,
arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of
autoimmune disorders including thyroiditis, RA, systemic lupus erythematosus,
psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and
pneumonia, some resulting in patient deaths), urticaria, angioedema,
bronchoconstriction, anaphylaxis, retinal hemorrhages, and cotton wool spots.
In the PEGINTRON/REBETOL
combination trial the incidence of serious adverse events was 17 percent in the
PEGINTRON/REBETOL groups compared to 14 percent in the INTRON A/REBETOL group.
The incidence of severe adverse events in the PEGINTRON/REBETOL combination
therapy trial was 23 percent in the INTRON A/REBETOL group and 31-34 percent in
the PEGINTRON/REBETOL groups. Dose reductions due to adverse reactions occurred
in 42 percent of patients receiving PEGINTRON (1.5 mcg/kg)/REBETOL and in 34
percent of those receiving INTRON A/REBETOL.
REBETOL should not be used in
patients with creatinine clearance less than 50 mL/min.
Schering-Plough is a global
science-based health care company with leading prescription, consumer and
animal health products. Through internal research and collaborations with
partners, Schering-Plough discovers, develops, manufactures and markets
advanced drug therapies to meet important medical needs. Schering-Plough's
vision is to earn the trust of the physicians, patients and customers served by
its approximately 33,500 people around the world. The company is based in
Kenilworth, N.J., and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE
NOTICE: The information in this press release includes certain
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements relating to the
company's strategy regarding and the potential of PEGINTRON, REBETOL and
boceprevir (SCH 503034). Forward-looking statements relate to expectations or
forecasts of future events. Schering-Plough does not assume the obligation to
update any forward-looking statement. Many factors could cause actual results
to differ materially from Schering-Plough's forward- looking statements,
including market forces, economic factors, product availability, patent and
other intellectual property protection, current and future branded, generic or
over-the-counter competition, the regulatory process, and any developments
following regulatory approval, among other uncertainties. For further details
of these and other risks and uncertainties that may impact forward-looking
statements, see Schering-Plough's Securities and Exchange Commission filings,
including Part I, Item 1A, "Risk Factors" in the company's 2006 10-K.
Source: Schering-Plough Corporation
April 12th,
2007
Data to be Presented April 15th at EASL Conference in Barcelona, Spain
VANCOUVER and SAN DIEGO, CA, April 11 /CNW/ -
MIGENIX Inc. (TSX: MGI, OTC: MGIFF), a clinical-stage developer of drugs for infectious
diseases, has received new top-line results confirming the previously announced
clinical results (November 6, 2006) indicating evidence of clinical benefit,
safety and tolerability in a Phase II study using the oral alpha-glucosidase
inhibitor, celgosivir (MX-3253), in combination with pegylated interferon and
ribavirin.
In addition to confirming the
overall conclusions of the original study analysis, retesting resulted in a
larger percentage of patients achieving an Early Virologic Response(*)
("EVR") rate with celgosivir plus peginterferon alfa-2b and ribavirin
(the "triple combination") as compared to treatment with
peginterferon alfa-2b and ribavirin alone (the "control treatment")
in patients with chronic hepatitis C virus genotype 1 infections who were
characterized as non-responders to prior therapy with optimized pegylated
interferon plus ribavirin, achieving:
·
42% (5/12) EVR with the celgosivir triple combination arm compared to
10% (1/10) EVR in the control treatment arm. This compares with 33% (4/12) EVR (triple combination) vs 10% (1/10)
(control treatment) in the original study results. (*) EVR = 2 log(10) or
greater HCV viral load reduction at 12 weeks.
·
1.63 log(10) (triple combination) mean HCV viral load reduction
("VLR") compared to a 0.92 log(10) VLR (control treatment). This
compares with a 1.2 log(10) VLR (triple combination) vs a 0.4 log(10) VLR
(control treatment) in the original study results.
·
a more rapid onset of treatment effect as measured by VLR within the
first 2 weeks of therapy in the triple combination as compared to the control
treatment.
These new top-line results
complete the retesting announced February 6, 2007 as a result of
Schering-Plough Corporation ("Schering") having informed MIGENIX that
approximately 50% of the original viral load samples from the study, which
Schering tested under a Material Transfer and License Option Agreement between
the companies, required retesting.
AnnKatrin Petersen, M.D., Vice
President, Clinical Development of MIGENIX stated, "the increase in EVR to
42% after retesting (33% previously) for the celgosivir triple combination
group in these very difficult to treat patients, along with the clear evidence
of rapid reduction in viral load give us increased confidence in the potential
of celgosivir to contribute in the treatment of HCV patients."
Jim DeMesa, M.D., President
and CEO of MIGENIX added, "This confirmation of our previously announced
results allows us to now focus on providing a data package to Schering-Plough
over the next few weeks for their limited period of exclusive review under our
License Option Agreement. The better EVR results seen upon retesting,
especially in these very difficult-to-treat non-responder patients, reinforces
our optimism in celgosivir's potential to improve treatment outcomes for these
HCV patients with few therapeutic options."
EASL Presentation
The results from this study
will be presented on April 15, 2007 at the 42nd Annual Meeting of the European
Association for the Study of the Liver (EASL) being held in Barcelona, Spain
April 11-15, 2007. The presentation entitled: "Phase II Proof of Concept
Study of Celgosivir in Combination with Peginterferon Alfa-2b and Ribavirin in
Chronic Hepatitis C Genotype-1 Non-responder Patients" will be made in the
General Session 4 on Sunday, April 15th from 1:00pm-1:15pm in Hall F of the
CCIB Conference Center. Dr. Kelly Kaita, the Director of the Viral Hepatitis
Investigative Unit (VHIU) at the Health Sciences Centre, University of Manitoba
and a lead investigator in the MIGENIX Phase II study will make the
presentation on behalf of MIGENIX.
Additional Information About the Clinical Study
The Phase II non-responder
combination study was designed to determine, over 12 weeks of treatment, the
efficacy, safety, and tolerability of celgosivir in combination with
peginterferon alfa-2b, with or without ribavirin, in HCV-positive (genotype 1)
patients who were non-responders or partial responders to prior therapy with
optimized pegylated interferon and ribavirin.
A total of 57 patients were
enrolled into this Phase II study (36 were non-responders and 21 were partial
responders). Patients were randomized into three treatment arms: (i) celgosivir
(400mg once daily) plus peginterferon alfa-2b plus ribavirin ("triple
combination"); (ii) celgosivir (400mg once daily) plus peginterferon
alfa-2b ("double combination"); and (iii) celgosivir placebo plus
peginterferon alfa-2b plus ribavirin ("control treatment"). Of the 36
non-responders, 30 patients completed the 12-weeks of treatment: 12 in the
triple combination arm, 8 in the double combination arm, and 10 in the control
treatment arm. Beyond the triple combination and control treatment results
reported above the following results were also consistent with the originally
reported results: (a) the double combination did not show a meaningful
difference in mean viral load reduction and EVR when compared to the control
treatment in non-responder patients; and (b) in the partial responder patient
population, there were insufficient patients (n=3) in the triple combination
arm for any conclusions to be drawn and the double combination showed less
effect than the control treatment.
Celgosivir combination therapy
was well tolerated and resulted in no significant adverse events. As expected
from previous experience, the most frequent side effects related to celgosivir
were gastrointestinal in nature and were generally mild. Other frequently
observed side effects were fatigue and flu-like symptoms - which are side
effects usually associated with pegylated interferon and ribavirin. Only 7 of
the 57 patients entering the study dropped out prior to week 12.
Material Transfer and License Option Agreement
Under the terms of the
Agreement, Schering supplied PEGETRON(TM) (peginterferon alfa-2b powder for
solution plus ribavirin 200 mg capsules) as well as certain technical and
laboratory support and other services for MIGENIX's celgosivir Phase II
combination study in chronic HCV patients and a related extension protocol. In
addition, the Agreement granted Schering limited periods of exclusivity for
data review of clinical trial results and for the negotiation of a license
agreement. With the new top-line results, we will be working to provide a data
package to Schering over the next few weeks, after which Schering's limited
period of exclusivity for data review under the Agreement will commence. No
license terms have been negotiated with Schering to date.
About Celgosivir (MX-3253)
Celgosivir is an alpha-glucosidase
I inhibitor and is currently the only anti-HCV drug in clinical development
that acts on host-directed glycosylation. In preclinical studies, celgosivir
has shown excellent in vitro synergy with various interferons in the clinic or
in development including Pegasys, PEG-Intron, Infergen, Alferon and IFN-omega
(with or without ribavirin) and other drugs in development for the treatment of
HCV (e.g. polymerase inhibitors) and therefore has the potential to be included
as part of many combination therapeutic approaches to improve efficacy in
anti-HCV therapy.
About HCV
HCV, the most common chronic
blood-borne infection in the United States, causes inflammation of the liver
and may progress to more serious complications such as cirrhosis of the liver,
liver cancer and death. Approximately 2.7 million people in the United States
are chronically infected with HCV, and the Centers for Disease Control and
Prevention (CDC) estimates that by the year 2010, the number of deaths
attributed annually to HCV could surpass that due to HIV/AIDS in the US.
Worldwide, the World Health Organization estimates that 170 million individuals
have chronic HCV infection, with 3 to 4 million new infections each year.
Therapy for HCV currently
employs a drug combination approach, which is anticipated to continue in the
future. The current standard of care for treatment-naive chronic hepatitis C is
pegylated interferon combined with ribavirin, which fails to provide a
satisfactory outcome for approximately 50% of patients infected with HCV
genotype 1 (the most prevalent genotype in North America). In addition, these
drugs can cause significant side effects that limit tolerance to therapy, or a
frequent lack of sustained treatment response.
About MIGENIX
MIGENIX is committed to
advancing therapy, improving health, and enriching life by developing and
commercializing drugs primarily in the area of infectious diseases. The
Company's clinical programs include drug candidates for the treatment of
chronic hepatitis C infections (Phase II and preclinical), the prevention of
catheter-related infections (Phase III) and the treatment of dermatological
diseases (Phase II). MIGENIX is headquartered in Vancouver, British Columbia,
Canada with US operations in San Diego, California. Additional information can
be found at www.migenix.com.
"Signed"
James M. DeMesa, M.D.
President & CEO
FORWARD-LOOKING STATEMENTS
This news release contains
forward-looking statements within the meaning of the United States Private
Securities Litigation Reform Act of 1995, and forward looking information
within the meaning of applicable securities laws in Canada, (collectively
referred to as "forward-looking statements"). Statements, other than
statements of historical fact, are forward-looking statements and include,
without limitation, statements regarding our strategy, future operations,
timing and completion of clinical trials, prospects, plans and objectives of
management. The words "anticipates", "believes",
"budgets", "could", "estimates",
"expects", "forecasts", "intends",
"may", "might", "plans", "projects",
"schedule", "should", "will", "would"
and similar expressions are often intended to identify forward-looking
statements, which include underlying assumptions, although not all
forward-looking statements contain these identifying words. By their nature,
forward-looking statements involve numerous assumptions, known and unknown
risks and uncertainties, both general and specific, that contribute to the
possibility that the predictions, forecasts, projections and other things
contemplated by the forward-looking statements will not occur.
Although our management
believes that the expectations represented by such forward-looking statements
are reasonable, there is significant risk that the forward-looking statements
may not be achieved, and the underlying assumptions thereto will not prove to
be accurate. Forward-looking statements in this news release include, but are
not limited to, statements concerning: our expectations regarding the time
required to complete and provide a data package of the celgosivir Phase II
study results to Schering; our expectations for the celgosivir Phase II study
results being presented on April 15, 2007 at the EASL conference; and celgosivir
having the potential to be included as part of many combination therapeutic
approaches to improve efficacy in anti-HCV therapy.
With respect to the
forward-looking statements contained in this news release, we have made
numerous assumptions regarding, among other things, our ability to successfully
complete the celgosivir Phase II data package for Schering within our expected
timelines, EASL accepting the new celgosivir Phase II results, the
competitiveness of the celgosivir study results to date and future results
supporting its potential in the treatment of HCV.
Actual results or events could
differ materially from the plans, intentions and expectations expressed or
implied in any forward-looking statements, including the underlying assumptions
thereto, as a result of numerous risks, uncertainties and other factors
including: uncertainties related to early stage of technology and product
development; uncertainties as to the requirement that a drug be found to be
safe and effective after extensive clinical trials and the possibility that the
results of such trials, if completed, will not establish the safety or efficacy
of our products; dependence on corporate collaborations; uncertainties as to
future expense levels and the possibility of unanticipated costs or expenses or
cost overruns; the possibility that opportunities will arise that require more
cash than presently anticipated and other uncertainties related to predictions
of future cash requirements; and other risks and uncertainties which may not be
described herein. Certain of these factors and other factors are described in
detail in the Company's Final Prospectus dated November 29, 2006, Annual
Information Form and Annual Report on Form 20-F for the year ended April 30,
2006 and other filings with the Canadian securities regulatory authorities and
the U.S. Securities & Exchange Commission.
Forward-looking statements are
based on our current expectations and MIGENIX assumes no obligations to update
such information to reflect later events or developments.
The Toronto Stock Exchange has
not reviewed and does not accept responsibility for the adequacy or accuracy of
this release.
For further information: Art
Ayres, MIGENIX Inc., Tel: (604) 221-9666
Ext. 233, aayres@migenix.com ; Dian Griesel
BARCELONA, Spain--(BUSINESS
WIRE)--Apr 11, 2007 - New data supporting the clinical development of
telaprevir (VX-950), one of the most advanced investigational oral protease
inhibitors for the treatment of hepatitis C virus (HCV) infection, will be
presented at the 42nd Annual Meeting of the European Association for the Study
of the Liver (EASL) in Barcelona this week. In total, nine abstracts related to
telaprevir have been accepted for presentation at the EASL conference,
including an abstract that describes telaprevir activity against genotypes 2, 3
and 4 in vitro. A late-breaker oral presentation will take place on Saturday,
April 14 at 5:45 p.m. Central European Summer Time (11:45 a.m. Eastern Daylight
Time). Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) is developing
telaprevir in collaboration with Tibotec.
"Hepatitis C is a major
global health problem with a significant unmet medical need. Despite treatment
advancements in the last 10 years, there is an urgent need for new therapeutic
options that can offer patients shorter course therapy and better
efficacy," said John Alam, M.D., Executive Vice President, Medicines
Development, and Chief Medical Officer of Vertex. "The data to be presented
at EASL demonstrate the recent progress made in our clinical evaluation and
understanding of telaprevir as a novel treatment for hepatitis C, underscoring
our commitment to evaluate telaprevir's potential in important sub-populations,
such as those with genotype non-1 hepatitis C."
Telaprevir is one of the most
advanced specifically targeted antiviral therapies for HCV (STAT-C). STAT-Cs
represent a new approach to hepatitis C treatment by directly targeting the
enzymes the virus uses to replicate.
Oral Presentation: Telaprevir Demonstrates Potency Against Genotype 2, 3
and 4 in vitro
Chao Lin, Ph.D., of Vertex,
will present an abstract titled, "Telaprevir (VX-950) is a Potent
Inhibitor of HCV-NS3 Proteases Derived from Genotype Non-1 HCV-Infected
Patients" at 6:15 p.m. CEST (12:15 p.m. EDT) on Thursday, April 12.
"While genotype 1
accounts for the majority of hepatitis C cases, the proportion of those living
with genotypes 2, 3 and 4 is significant," continued Dr. Alam. "In
this in vitro study, telaprevir demonstrated similar potency against the NS3-4A
protease derived from those patients with genotype 2, 3 and 4 to the in vitro
results demonstrated with telaprevir in genotype 1. These results support our
plans to begin to study telaprevir in genotypes 2, 3 and 4 in 2007."
Late-Breaker Presentation
A late-breaker presentation
titled, "Results of an Interim Analysis of a Phase 2 Study of Telaprevir
(VX-950) with Peginterferon alfa-2a and Ribavirin in Previously Untreated
Subjects with Hepatitis C," will be presented by John McHutchison, M.D.,
Principal Investigator for the PROVE 1 study and Director of Gastroenterology
and Hepatology Research at Duke Clinical Research Institute, on Saturday, April
14 at 5:45 p.m. CEST (11:45 a.m. EDT).
In accordance with EASL
embargo policy, these data remain under embargo until conclusion of the
late-breaker session on Saturday, April 14 at 6:00 p.m. CEST (12:00 p.m. EDT).
Additional Telaprevir Presentations
Additional data presented at
EASL will include viral kinetic data that continue to support further
evaluation of telaprevir-based therapy to clear the hepatitis C virus with
shorter treatment duration, and in vivo and in vitro viral replication and
viral sequencing dynamic modeling studies that suggest telaprevir-resistant
variants have reduced replication capacity compared to wild-type HCV. Poster
presentations will begin on Thursday, April 12.
-- "Novel Mode of Viral
Decline During Telaprevir (VX-950) and Peg-IFN Combination Treatment Predicted by
a New Combined Intracellular and Cellular Hepatitis C Viral Dynamics
Model," will be presented by A.U. Neumann of Bar-llan University, Israel.
-- "Telaprevir
(VX-950)-Resistant Variants Exhibit Reduced Replication Capacity Compared to
Wild-Type HCV in Vivo and In Vitro," will be presented by Chao Lin of
Vertex.
-- "Ultrasound Evaluation
of Perihepatic Lymph Nodes During Antiviral Therapy with the Protease Inhibitor
Telaprevir (VX-950) in Patients with Chronic Hepatitis C Infection," will
be presented by Mireen Friedrich-Rust and Nicole Forestier, Saarland University
Hospital, Germany.
-- "Neopterin and ALT as
Markers of Inflammation in Chronic Hepatitis C Patients During Administration
of the HCV NS3-4A Protease Inhibitor Telaprevir (VX-950) in Combination with
PegInterferon Alpha 2A," will be presented by Huub Gelderblom, University
of Amsterdam.
-- An oral presentation
titled, "Molecular Basis for VX-950 Resistance," will be presented by
Stefan Zeuzem, Saarland University Hospital, Germany, at 5:15 p.m. CEST (11:15
a.m. EDT) on Friday, April 13.
Two presentations discussing
in vitro data of telaprevir in combination with other oral direct antiviral
therapies will also take place during EASL.
Full abstracts are available
on the EASL website: www.easl.ch/liver-meeting
.
Webcast of Investor Presentation
Vertex intends to provide a
live webcast of its investor presentation from Barcelona beginning at 7:30 p.m.
CEST (1:30 p.m. EDT) on Saturday, April 14. The presentation may be accessed
from the 'Events Calendar' on the homepage of Vertex's website at www.vrtx.com.
A replay of the webcast will also be available on the Company's website until
April 27, 2007. To ensure a timely connection, it is recommended that users
register at least 15 minutes prior to the scheduled webcast.
About Telaprevir (VX-950)
Telaprevir (VX-950) is an
investigational oral inhibitor of HCV protease, an enzyme essential for viral
replication, and is one of the most advanced investigational agents in
development that specifically targets HCV. Vertex is conducting a global Phase
2b clinical development program for telaprevir consisting of three large
clinical trials that are expected to enroll approximately 1,000 patients with
HCV at clinical centers in the U.S., Canada and E.U. In February 2007, Vertex
announced the initiation of PROVE 3, designed to enroll 440 genotype-1 HCV
patients who have previously received interferon based therapy in the U.S.,
Canada and E.U. Vertex completed enrollment of 250 patients in the U.S.-based
PROVE 1 trial in September 2006. The 320-patient, European-based PROVE 2 trial
completed enrollment in January 2007. In these clinical trials, telaprevir is
being dosed as 750 mg every 8 hours in combination with peginterferon alfa-2a
(Pegasys(R)), both with and without ribavirin (Copegus(R)).
Vertex retains commercial
rights to telaprevir in North America. Vertex and Tibotec are collaborating to
develop and commercialize telaprevir in Europe, South America, Australia, the
Middle East, and other countries. Vertex is collaborating with Mitsubishi
Pharma to develop and commercialize telaprevir in Japan and certain Far East
countries.
About Hepatitis C
Hepatitis C is a liver disease
caused by infection with hepatitis C virus (HCV), which is also found in the
blood of people with the disease. HCV, a serious public health concern
affecting 170 million people worldwide, is spread through direct contact with
the blood of an infected person. Though many people with hepatitis C may not
experience symptoms, others may have symptoms late in the course of the disease
such as jaundice, abdominal pain, fatigue and fever. Hepatitis C significantly
increases a person's risk of developing chronic liver disease, cirrhosis, liver
cancer and early death.
About Vertex
Vertex Pharmaceuticals
Incorporated is a global biotechnology company committed to the discovery and
development of breakthrough small molecule drugs for serious diseases. The
Company's strategy is to commercialize its products both independently and in
collaboration with major pharmaceutical companies. Vertex's product pipeline is
focused on viral diseases, inflammation, autoimmune diseases, cancer, pain and
bacterial infection. Vertex co-discovered the HIV protease inhibitor, Lexiva,
with GlaxoSmithKline.
Vertex's press releases are
available at www.vrtx.com .
About Tibotec
Tibotec Pharmaceuticals Ltd.,
based in Cork, Ireland, is a pharmaceutical research and development company.
Tibotec is dedicated to the discovery and development of innovative HIV/AIDS
drugs and anti-infectives for diseases of high unmet medical need. The
Company's main research and development facilities are in Mechelen, Belgium
with offices in Yardley, PA.
For further information on
Tibotec, please visit: www.tibotec.com
Safe Harbor Statement
This press release may contain
forward-looking statements, including statements that (i) non-clinical, in
vitro studies evaluating telaprevir against NS3 4A proteases in patients with
genotype 2, 3 and 4 support Vertex's planned clinical evaluation of TVR in
other genotypes; (ii) viral kinetic data will continue to support further
evaluation of telaprevir combination therapy to clear the virus with shorter
treatment duration; (iii) in vivo and in vitro viral replication and viral
sequencing dynamic modelling studies suggest that telaprevir-resistant variants
have reduced replication capacity compared to wild-type HCV; and (iv) Vertex
expects the combined PROVE program to increase to more than 1,000 the number of
patients in telaprevir clinical trials. While management makes its best efforts
to be accurate in making forward-looking statements, such statements are
subject to risks and uncertainties that could cause the actual results of
studies to vary materially. Those risks and uncertainties include, among other
things, the risk that observed outcomes in in vitro analyses or in clinical
investigations of small numbers of patients will not be reflected in clinical
trials involving larger numbers of patients, that unexpected and adverse
outcomes in other ongoing clinical and nonclinical studies, and other risks
listed under Risk Factors in Vertex's Form 10-K filed with the Securities and
Exchange Commission on March 1, 2007. Vertex disclaims any obligation to update
the information contained in this press release as new data become available.
Contact
Vertex Contacts:
Lynne H. Brum, 617-444-6614
VP, Strategic Communications
or
Michael Partridge,
617-444-6108
Director, Corporate
Communications
or
Lora Pike, 617-444-6755
Manager, Investor Relations
or
Patricia Farrell, 617-444-6533
Director, Public Relations
or
Zachry Barber, 617-444-6470
Senior Media Relations
Specialist
or
Tibotec Contact:
Karen Manson, +32 15 461 019
Mobile +32 479 894 799
VP, Communications and Public
Affairs
Potent Synergy, Activity and Patient Tolerance Support Development of
Omega DUROS(R) Continuous Delivery Therapy
BARCELONA, Spain, April 12
/PRNewswire/ -- Intarcia Therapeutics, Inc., a privately held biopharmaceutical
company, today announced final results from a Phase 2 study of omega interferon
with or without ribavirin in treatment-naive patients with genotype 1 chronic
hepatitis C. The results demonstrate that omega interferon in combination with
ribavirin is well tolerated and show robust antiviral activity that is
comparable to published data on the use of alpha interferon plus ribavirin in
similar patient populations. The 72-week sustained viral response (SVR) data
are being presented today at the 42nd annual meeting of the European
Association for the Study of the Liver (EASL) in Barcelona, Spain by John
McHutchison, MD, Associate Director, Duke Clinical Research Institute and
Professor of Medicine, Duke University Medical Center, Durham, North Carolina.
This Phase 2 study of daily
subcutaneous omega interferon injections provides Intarcia with safety and
clinical response data to support continued development of omega interferon
delivered by continuous release from the DUROS(R) device.
"The safety and SVR rates
achieved in this phase 2 study suggest that omega interferon plus ribavirin may
achieve similar effects to alpha interferon and ribavirin in patients with HCV
genotype-1," said Dr. McHutchison. "We look forward to results of the
planned study of Omega DUROS therapy in which we will evaluate optimization of
dose and pharmacokinetics through the delivery of omega interferon with the
implantable DUROS device."
The Phase 2 trial compared the
safety and antiviral response of omega interferon alone with omega interferon
in combination with ribavirin in 102 interferon-naive patients in an
open-label, multi-center, active-controlled study design. All study patients
had genotype-1, the most treatment-resistant type of HCV, and the majority of
patients (74%) had high baseline viral load ( > 800,000 IU/ml), a
well-established negative predictive factor for SVR. Patients received daily
injections of omega interferon (25 mcg) for up to 48 weeks. The endpoints for
this clinical trial were early viral response (EVR), defined as a 2-log
reduction in HCV RNA after 12 weeks of treatment, and SVR, defined as
undetectable HCV RNA 24 weeks after the end of 48 weeks of treatment. Response
rates are presented in the table below:
|
HCV RNA
Results |
Omega
IFN + RBV |
Omega
IFN Alone |
|
(LOQ=
50 IU/ml) |
N=67 |
N=35 |
|
|
|
|
|
Early Viral Response (EVR) |
84% |
60% |
|
|
|
|
|
Sustained Viral Response(SVR) |
36% |
6% |
With this study, Intarcia also
took a step toward testing its hypothesis that maintaining continuous drug
levels through daily administration of omega interferon may minimize side
effects when compared to current interferon therapies. This study to date has
shown that omega interferon is well tolerated with only two discontinuations
due to adverse events. Results of this Phase 2 study suggest a favorable
overall safety profile with no substantial safety issues being identified.
Normalization of serum ALT, a marker of reduced liver inflammation, occurred in
100% of patients achieving SVR and no patients receiving omega interferon with
ribavirin experienced relapse during 24 weeks of follow-up after completing 48
weeks of treatment.
Alice Leung, President and
Chief Executive Officer of Intarcia stated, "We are developing omega
interferon to improve the treatment of HCV by offering a more convenient,
potentially safer and more efficacious therapy. Based on the data so far, we
believe that a continuous release formulation of omega interferon has the
potential to become an important therapy for HCV patients."
About Omega DUROS Therapy
Omega DUROS therapy is being
developed to improve the treatment of HCV by offering a more convenient and
potentially safer and more effective treatment. Omega DUROS therapy is designed
to deliver a continuous and consistent dose of omega interferon for three
months via the implantable DUROS device, a drug delivery technology developed
by ALZA Corporation, and licensed to Intarcia for use in certain broad fields.
Another product incorporating the DUROS technology has already approved by the
FDA for the palliative treatment of prostate cancer. Intarcia is also leveraging
the DUROS technology in evaluating other drug development opportunities. The
most advanced of these is focused on the delivery of GLP-1 and a GLP-1 analog
with the DUROS device for the treatment of type 2 diabetes.
About Intarcia
Intarcia Therapeutics, Inc. is
a biopharmaceutical company developing therapeutics for patients with chronic
diseases in which there are significant unmet medical needs. Intarcia's drug
development expertise and competitive edge are complemented by its ability to
stabilize macromolecules and to deliver them in a constant and consistent
manner via the proprietary DUROS drug delivery platform. The initial programs
that Intarcia is pursuing are in hepatitis C and type 2 diabetes.
About Hepatitis C
Hepatitis C is a major global
public health problem. According to the World Health Organization, more than
170 million people worldwide are chronically infected with HCV, and three to
four million new HCV infections occur annually. The U.S. Centers for Disease
Control and Prevention has estimated that in the United States approximately
3.4 million people are chronically infected with HCV and approximately 25,000
new patients are infected each year. It is estimated that 10,000 to 12,000
patients die annually in the United States from complications resulting from
HCV infection. The current standard of care for treating chronic hepatitis C is
combination therapy consisting of pegylated alpha interferon and ribavirin.
About Diabetes
Diabetes affects more than 20
million in the United States and an estimated 194 million adults worldwide.
Approximately 90-95 percent of those affected have type 2 diabetes. Diabetes is
the fifth leading cause of death by disease in the United States. According to
the U.S. Centers for Disease Control and Prevention's National Health and
Nutrition Examination Survey, approximately 60 percent of people with diabetes
do not achieve target A1c levels with their current treatment regimen.
DUROS is a registered
trademark of ALZA Corporation (Mountain View, CA) licensed to Intarcia
Therapeutics, Inc. Intarcia and its logo are trademarks of Intarcia
Therapeutics, Inc. (Emeryville, CA).
SOURCE Intarcia Therapeutics, Inc.
By ED SUSMAN
BARCELONA, Spain, April 12
(UPI) -- Researchers meeting in Spain said Thursday that hepatitis C patients
who achieve a complete response to treatment can be considered completely cured
of the disease that can result in cirrhosis, liver failure and death.
"I tell my patients who
achieve a sustained virologic response to go home and get on with their
lives," said Mark Swain, professor of medicine at the University of
Calgary in Canada, who presented results of an international trial at the
opening session of the 42nd European Association for the Study of the Liver in
Barcelona, Spain. "I tell them that there is less than a 0.5 percent chance
that the disease will ever return."
In fact, of 997 patients who
were able to achieve the complete response, only 8 came down with the disease
again, Swain said.
"This is a very important
message. We can cure people with this disease," Xavier Forns, senior
specialist in liver diseases at the Hospital Clinic in Barcelona and a member
of the program committee for the conference, told United Press International.
"We made this paper
'Abstract 1' because we thought this was a significant finding that is important
to our patients and to the clinicians."
Swain identified the 997
patients from 9 clinical trials that tested drugs either in monotherapy or in
combination therapy. All these patients had a sustained virologic response when
treated with pegylated interferon alfa-2a (PEGASYS) as monotherapy or in
combination with ribavirin (COPEGUS). The criteria for a sustained virologic
response means that after taking drugs for either six months or 24 months,
tests could not detect virus in the bloodstream. If six months after stopping
the drugs there was still no detectable virus, the patient was said to have
achieved a sustained virologic response.
Swain said that such patients
should also be told that can be considered cured.
The study included three
trials in which patients were treated with monotherapy and six trials in which
the combination treatment was employed. Swain said the combination therapy is
now considered standard of care and as many as 66 percent of patients infected
with hepatitis C who faithfully take their antiviral medication -- usually for
48 weeks -- are able to achieve the sustained virologic response.
"Although the benefits of
viral eradication have been well established, the overall durability of a
sustained virologic response is less well known," Swain explained.
Of the patients who did
achieve a sustained virologic response, 163 patients who only had hepatitis C
infections were treated with peginterferon alfa-2a monotherapy; 741 patients
were treated with peginterferon alfa-2a monotherapy plus ribavirin combination
therapy; 93 patients co-infected with human immunodeficiency virus (HIV) and
hepatitis C were treated with either monotherapy or combination therapy.
"We found that a
sustained virologic response is a sustained virologic response whether it
occurs in an immunosuppressed patient due to disease such as HIV, or who has
undergone transplantation and requires immunosuppressive drugs," Swain
said. There was no falloff in response. Of the eight people who relapsed or
were re-infected, just one patient in the combined hepatitis C-HIV group was
listed as a relapse. He also noted that only one of the eight cases involved a
patient who had taken a full course of treatment.
Swain said that, due to the
way the studies were conducted, it will be impossible to determine if the
patients indeed relapsed or were re-infected. In only one case did a patient's
records contain viable virus for a DNA comparison to be made. In that case, the
patient appeared to become re-infected with a different strain of hepatitis C.
"We are never going to know the answer to whether these are relapses or
re-infections," he said.
Forns told UPI that hepatitis
can be contracted through injected drug use, sexual contact and hospital-acquired
infections. He said that patients need to be aware, however, that a cure does
not mean that re-infection can't occur if they continue to have risky
activities.
Idenix Reports Midstage Studies on Hepatitis C Candidate Showing Mixed
Results
CAMBRIDGE, Mass. (AP) -- Drug
developer Idenix Pharmaceuticals Inc. said Thursday two studies of a treatment
for Hepatitis C yielded mixed results, with the drug failing to show efficacy
in one trial but demonstrating "encouraging" results in another,
ongoing study.
Idenix was conducting two
midstage Phase IIb clinical trials for the company's valopicitabine and Pegasys
combination. The first trial involved 173 patients who had not previously been
treated with the combination of valopicitabine and Pegasys, or pegylated
interferon alfa-2a. Fifty-three percent of patients responded to the treatment
at the end of the 48-week course. The study is still ongoing and Idenix will
measure the response rate at 6 months after ending treatment to determine
effectiveness.
The current standard of care
in the field, which involves combining pegylated interferon alfa and ribavirin,
yields a response rate of between 42 percent and 46 percent.
The second trial, involving
178 patients who previously received treatment, failed to meet its goal, with
no patients responding to the treatment. The comparison for that trial involved
the drug ribavirin, which the company has added in another study to the drug
combination.
Idenix called the data
"encouraging," and said further studies are warranted to determine
the relevance of all findings.
"We remain optimistic
about the antiviral activity of the combination of valopicitabine and pegylated
interferon (Pegasys) observed in various patient populations, and believe that
multi-drug combinations will play an important role in the treatment of
Hepatitis C genotype-1 infected patients," said Douglas L. Meyers, chief
medical officer. "We are now working to define valopicitabine's role in
therapy, not only in combination with the current standard of care, but also
with other investigational compounds in development."
Shares of Idenix fell 39
cents, or 4.8 percent, to $7.76 on the Nasdaq Stock Market in midday trading.
The stock has traded between $7.18 and $12.22 over the last 52 weeks.
April 13th,
2007
ViroPharma Inc said new data
showed one of its oral compounds designed to treat chronic hepatitis C had
additional antiviral effects across multiple virus strains when combined with
another therapy.
The Exton, Pa., pharmaceutical
company said Friday that the results of the 14-day Phase Ib trial indicated
that the HCV-796 compound was more effective in combination with pegylated
interferon alfa-2b than when either of the drugs was administered alone.
The combination therapy is
generally well tolerated and no dose-limiting toxicities were observed, the
company said.
A Phase II trial of HCV-796,
which is being jointly developed with the Wyeth Pharmaceuticals unit of Wyeth
-Contact: 201-938-5400
High Response Rates Confirmed in 'Real-Life' Study and Clinical Trials
BASEL, Switzerland, April 13
/PRNewswire/ --
Patients with hepatitis C who
respond quickly to treatment have an excellent chance of being cured of the
disease, according to data presented today at the 42nd Annual Meeting of the
European Association for the Study of the Liver (EASL). Patients with genotype
1 hepatitis C (HCV) who clear the virus within a month of starting treatment
with PEGASYS (peginterferon alfa-2a (40KD)) plus COPEGUS (ribavirin) have up to
a 91% chance of achieving a sustained virological response (SVR), considered a
cure by researchers.
"Now we can tell earlier
than ever - at just week 4 of treatment - whether a patient has a good chance
to be cured." said Professor Patrick Marcellin, Hôpital Beaujon, Clichy,
France. "Knowing their virus levels in the first and third months of
treatment helps patients take ownership of beating the disease and helps
motivate them to stay on treatment. This information should be made available
for everyone starting therapy."
Early Response to Treatment Means Patients Have an Excellent Chance for
a Cure
An analysis of six different
clinical trials highlights the value of checking how well patients with
genotype 1 HCV have responded to treatment at weeks 4 and 12 of therapy(1). The
results of the analysis showed that of
those patients treated with PEGASYS 180 mcg weekly plus COPEGUS 1,000-1,200 mg daily:
·
Up to one in five cleared the virus by week 4 of therapy (called rapid
viral response)
·
83-91% of patients with a rapid viral response went on to be cured of
their hepatitis C
·
About 40% of patients who did not achieve a rapid viral response managed
to clear the virus by week 12 of therapy (called complete early virological
response); 65-67% of these patients were cured
Excellent Chance for a Cure for Rapid Viral Responders Confirmed in
'Real-Life' Study
A large real-life study
involving 4,377 patients conducted by the Association of German Independent
Gastroenterologists confirms that these results can be replicated in clinical
practice(2):
·
One quarter of patients with 'difficult-to-cure' genotype 1 or 4 HCV who
had their viral levels tested at week 4 of treatment achieved a rapid viral
response
·
While the study is not yet complete, over 70% of those who have finished
their 6-month post-treatment follow-up period were cured
·
"These are really important results," said Dr Elmar Zehnter,
Gastroenterologist and Hepatologist, Dortmund, Germany, and researcher in the
study. "This study confirms that the high cure rates reported for rapid
viral responders in clinical trials translate into clinical practice and are relevant
to the patients we see every day. At the moment, testing viral levels at 4
weeks of treatment is not standard practice. Based on these results, however,
testing viral levels at 4 weeks of therapy should become a routine test."
About Hepatitis C
Hepatitis C, the most common
chronic blood-borne infection, is transmitted primarily through blood or blood
products. Hepatitis C chronically infects 180 million people worldwide, which
makes it more than four times more prevalent than HIV(3,4). Alarmingly, many
people infected with hepatitis C don't
even know they carry the virus. For example, it is estimated that 80-90% of
people with hepatitis C in the UK are unaware that they are infected(5).
Hepatitis C is a leading cause of cirrhosis, liver cancer and liver failure, despite the fact
that many patients can be cured with
treatments that are available today.
About PEGASYS
PEGASYS, the market leader
worldwide in hepatitis C therapy, provides significant benefit over
conventional interferon therapy in HCV patients of all genotypes. The benefits
of PEGASYS are derived from its 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. PEGASYS is
the only pegylated interferon available as a ready-to-administer solution. Each
weekly subcutaneous injection contains 180 mcg of pegylated interferon alfa-2a
(40KD), which is the approved dose for all patients, regardless of body weight.
About Roche
Headquartered in Basel,
Switzerland, Roche is one of the world's leading research-focused healthcare
groups in the fields of pharmaceuticals and diagnostics. As the world's biggest
biotech company and an innovator of products and services for the early
detection, prevention, diagnosis and treatment of diseases, the Group
contributes on a broad range of fronts to improving people's health and quality
of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer
and transplantation, a market leader in virology and active in other major
therapeutic areas such as autoimmune diseases, inflammation, metabolism and
central nervous system. In 2006 sales by the Pharmaceuticals Division totalled
33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7
billion Swiss francs. Roche employs roughly 75,000 worldwide and has R&D
agreements and strategic alliances with numerous partners, including majority
ownership interests in Genentech and Chugai.
Additional information about
the Roche Group is available on the Internet at www.roche.com
.
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References
1. Marcellin P, Hadziyannis S,
Berg T, et al. Virological response at 4 and 12 weeks predict high rates of
sustained virological response in genotype 1 patients treated with
peginterferon alfa-2a (40KD) plus ribavirin. In: 42nd Annual Meeting of the
European Association for the Study of the Liver; 2007 April 11-15; Barcelona,
Spain; 2007.
2. Zehnter E, Mauss S, Boeker
K, et al. Potential relevance of rapid viral response for SVR and optimisation
of the treatment of hepatitis C (CHC) with peginterferon alfa-2a (PEG) and
ribavirin (RBV). In: 42nd Annual Meeting of the European Association for the
Study of the Liver; 2007 April 11-15; Barcelona, Spain; 2007.
3. AIDS Epidemic Update. 2006.
(Accessed February 27, 2007, at http://www.who.int/hiv/mediacentre/2006_EpiUpdate_en.pdf.)
4. Initiative for Vaccine
Research, Viral Cancers, Hepatitis C. World Health Organization, 2006.
(Accessed July 24, 2006, at http://www.who.int/vaccine_research/diseases/viral_cancers/en/index2.html
.)
5. The hepatitis C scandal.
London: All-Party Parliamentary Group on Hepatology; 2004.
ots Originaltext: Roche Pharmaceuticals
Im Internet recherchierbar: http://www.presseportal.de
Contact:
Contact: Janet Kettels, Roche, +1-862-596-9084;
Natalie Henson, Axon
Communications, +44(0)20-843-99-406
Additional Preclinical Data Presented on Valopicitabine Combined with an
Investigational Protease Inhibitor
BARCELONA, Spain, April 12
/PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX) today
announced results from two phase IIb studies of the novel combination of
valopicitabine (NM283) and pegylated interferon alfa-2a (Pegasys(R)) in both
treatment-naive and treatment- experienced patients infected with the
genotype-1 strain of the hepatitis C virus (HCV). These data, as well as
preclinical data on the active component of valopicitabine in combination with
Schering Plough's investigational protease inhibitor boceprevir (SCH 503034),
will be presented at the 42nd Annual Meeting of the European Association for
the Study of the Liver (EASL).
Pegylated interferon alfa and
ribavirin therapy, the current standard of care, is successful in treating 42 -
46 percent of treatment-naive HCV genotype-1 infected patients.(1,2) For
patients who do not achieve successful treatment outcomes with pegylated
interferon and ribavirin, there are currently no approved treatment options.
New antiviral agents are needed to provide more treatment options for patients
infected with HCV genotype-1.
"We have learned a great deal
about the treatment of patients with hepatitis C, as well as the safety and
efficacy of valopicitabine as a result of these large phase IIb trials,"
said Douglas L. Mayers, executive vice president and chief medical officer of
Idenix Pharmaceuticals. "We remain optimistic about the antiviral activity
of the combination of valopicitabine and pegylated interferon observed in
various patient populations, and believe that multi-drug combinations will play
an important role in the treatment of HCV genotype-1 infected patients. We are
now working to define valopicitabine's role in therapy, not only in combination
with the current standard of care, but also with other investigational
compounds in development."
48-Week End-of-Treatment Results in Study of Treatment-Naive Patients
The first study, which was
conducted at 23 sites in the United States, evaluated the safety and efficacy
of various doses of valopicitabine plus pegylated interferon in 173 HCV
genotype-1 infected, treatment-naive patients over 48 weeks. The primary
endpoint of the study is sustained virologic response (SVR), defined as
maintained viral clearance six months after treatment is stopped. At the end of
the treatment period, which was 48 weeks, 53 percent (n=18/34) of patients
treated with 200 mg/day valopicitabine plus pegylated interferon achieved
undetectable HCV levels by the TaqMan(R) assay (<20 IU/mL).
"These data are
encouraging," said Eric Lawitz, M.D., medical director, Alamo Medical
Research. "It is important to remember that ribavirin was not used in this
study. The addition of ribavirin to the combination of valopicitabine and
pegylated interferon may increase on-treatment response and may help to prevent
post-treatment relapse. I look forward to the results from the company's ongoing
study exploring the triple combination."
Through 48 weeks of treatment,
38 out of a total of 173 patients discontinued from the trial for adverse
events (AEs), mostly gastrointestinal (GI)-related; of these, 3 patients were
receiving the 200 mg/day dose of valopicitabine. Seven serious adverse events
(SAEs) were assessed as attributable to either valopicitabine or valopicitabine
and pegylated interferon during the first 48 weeks of treatment, most of which
were GI- related. In this study, no valopicitabine-related GI SAEs have
occurred since March 2006, when this study was amended to reduce the dose of
valopicitabine administered to 200 mg/day or 400 mg/day.
Final Results in Study of Treatment-Experienced Patients
The second phase IIb clinical
trial, which was conducted at 22 sites in the United States, evaluated various
doses of valopicitabine in combination with pegylated interferon compared to
pegylated interferon and ribavirin in 178 HCV genotype-1 infected,
treatment-experienced patients for a treatment duration of up to 72 weeks. The
primary endpoint of the study was SVR, defined as maintained viral clearance
six months after treatment is stopped. The end- of-treatment response rates and
post-treatment SVR rates were comparable for patients receiving valopicitabine
and pegylated interferon and those receiving pegylated interferon and
ribavirin. Of patients treated with valopicitabine in combination with
pegylated interferon, none achieved an SVR, compared to one patient retreated
with pegylated interferon and ribavirin.
Of the patients enrolled in
this trial, 16 percent were partial responders, meaning they achieved a greater
than or equal to 2 log reduction but never cleared the virus during their prior
course of pegylated interferon and ribavirin therapy, and 84 percent were prior
null responders, meaning they had never achieved a 2 log reduction in virus
levels. In this study, 42 percent (n=10/24) of prior partial responders treated
with valopicitabine and pegylated interferon achieved PCR-negativity at the
end-of-treatment, compared to 16 percent (n=19/120) of prior null responders
treated with valopicitabine and pegylated interferon.
"These data are
significant as they underscore the difficulty in retreating patients who have
failed standard of care," said Nezam Afdhal, M.D., chief of hepatology and
director of the liver center, Beth Israel Deaconess Medical Center. "There
was a significant antiviral response to the combination of valopicitabine plus
pegylated interferon in prior partial responders which is encouraging. Based on
these data, further studies are warranted to assess if the addition of
ribavirin and potentially another investigational agent to this treatment
regimen could offer partial responders/relapsers to prior therapy a viable treatment
option."
In this study, 31 out of a
total of 178 patients discontinued from the trial for AEs, of which 12 were
GI-related. Seven SAEs were assessed as attributable to either valopicitabine
or valopicitabine and pegylated interferon during this study, most of which
were GI-related. In this study, no valopicitabine-related GI SAEs occurred
after March 2006, when this study was amended to reduce the dose of
valopicitabine administered to 400 mg/day.
Preclinical Data in Combination with an Investigational Protease
Inhibitor
A separate study presented at
EASL evaluated the combined antiviral effect of the active component of
valopicitabine, NM107, and SCH 503034, Schering Plough's investigational
protease inhibitor currently in phase II trials, using cell culture replicon
studies. The in vitro results demonstrated that the combination of these two
agents provided additive antiviral activity compared to either agent used
alone, with no cross resistance. Additionally, the combination of SCH 503034
and NM107 significantly reduced the frequency of resistant colonies, compared
to each agent used alone, indicating that the combination of the two agents
increased the barrier for developing resistance to either drug. Further studies
are warranted to determine the clinical relevance of these findings.
About Valopicitabine (NM283)
Valopicitabine is an
investigational HCV RNA polymerase inhibitor being evaluated in ongoing
clinical trials for the treatment of hepatitis C. The most common adverse
events reported in the phase IIb studies included nausea, vomiting, fatigue,
diarrhea, headache, flu-like symptoms and depression. In the phase IIb studies,
the occurrence of GI-related adverse events appeared to be dose dependent, and
was less frequent in patients receiving 200 mg/day or 400 mg/day of
valopicitabine. Idenix is developing valopicitabine in collaboration with
Novartis Pharma AG.
About Hepatitis C
HCV infection is the most
common chronic blood-borne infection in the United States.(3) The Centers for
Disease Control and Prevention estimates that 4 million Americans have been
infected with HCV, and 2.7 million of these carry chronic HCV infections.(4)
Hepatitis C-related liver failure is the most common indication for liver
transplantation in the United States.(4) As the prevalence of severe liver
disease attributable to hepatitis C rises, deaths due to complications from
hepatitis C infection, currently 8,000 to 10,000 per year in the United States,
are increasing and are expected to triple by 2010.(5)
About Idenix
Idenix Pharmaceuticals, Inc.,
headquartered in Cambridge, Massachusetts, is a biopharmaceutical company
engaged in the discovery, development and commercialization of drugs for the
treatment of human viral and other infectious diseases. Idenix's current focus
is on the treatment of infections caused by hepatitis B virus, hepatitis C
virus and human immunodeficiency virus (HIV). For further information about
Idenix, please refer to http://www.idenix.com/
.
Forward-looking Statement
This press release contains
"forward-looking statements" within the meaning of The Private
Securities Litigation Reform Act of 1995. Such forward-looking statements can
be identified by the use of forward-looking terminology such as
"suggest," "can," "believe,"
"encouraging," "provide," "expect,"
"will," "look forward to," or similar expressions, or by
express or implied statements with respect to potential results of on-going
clinical trials of NM283, approvals of NM283 by the United States or other
regulatory bodies, or potential future revenues from NM283. Such
forward-looking statements involve known and unknown risks, uncertainties and
other factors that may cause actual results to be materially different from any
future results, performance or achievements expressed or implied by such
statements. There can be no guarantees that Idenix will successfully advance
NM283 or any clinic product candidate or other component of our potential
pipeline in the clinic or in the regulatory process. In particular,
management's expectations could be affected by unexpected regulatory actions or
delays; uncertainties relating to results of clinical trials, including
additional data relating to the ongoing clinical trials evaluating NM283 and its
other product candidates; the company's ability to obtain additional funding
required to conduct its research, development and commercialization activities;
the company's dependence on its collaboration with Novartis Pharma AG; the
ability of the company to attract and retain qualified personnel; competition
in general; and the company's ability to obtain, maintain and enforce patent
and other intellectual property protection for its other product candidates and
its discoveries. These and other risks which may impact management's
expectations are described in greater detail under the caption "Risk
Factors" in the company's annual report on Form 10-K for the year ended
December 31, 2006 and filed with the Securities and Exchange Commission and other
filings that the company makes with the Securities and Exchange Commission.
All forward-looking statements
reflect the company's expectations only as of the date of this release and
should not be relied upon as reflecting the company's views, expectations or
beliefs at any date subsequent to the date of this release. Idenix anticipates
that subsequent events and developments may cause these views, expectations and
beliefs to change. However, while Idenix may elect to update these
forward-looking statements at some point in the future, it specifically
disclaims any obligation to do so.
Pegasys(R) is registered
trademarks of Hoffmann-La Roche, Inc. TaqMan(R) is a registered trademark of
Roche Molecular Systems, Inc.
1 Fried, M. et al., Peginterferon Alfa-2a Plus Ribavirin
for Chronic Hepatitis C Virus Infection. New England Journal of Medicine 2002.
2 Manns, M. Peginterferon Alfa-2b Plus Ribavirin
Compared with Interferon Alfa-2b Plus Ribavirin for Initial Treatment of
Chronic Hepatitis C: A Randomized Trial. The Lancet, September 2001.
3 Center For Disease Control National Prevention
Strategy.
4Center for Disease Control. Hepatitis C Fact Sheet
accessed online at http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm
.
5 Davis, G. et al., Projecting Future Complications of
Chronic Hepatitis C in the United States. Liver Transplantation, April 2003.
Idenix Pharmaceuticals' Contacts: Media: Teri Dahlman (617) 995-9905 Investors:
Amy Sullivan (617) 995-9838
Website: http://www.idenix.com/
By Jill Stein
BARCELONA, SPAIN -- April 13, 2007 -- Higher doses of
ribavirin (i.e., 1000/1200 mg/d) are in patients with hepatitis C virus
genotype 1, researchers reported here at the 42nd Annual Meeting of the
European Association for the Study of the Liver (EASL).
Samuel Lee, MD, professor, division of medicine,
University of Calgary, Calgary, Alberta, Canada, presented the results from a
study evaluating 24 to 48 weeks of treatment with peginterferon alfa-2A 180
mcg/week plus ribavirin as part of an open-label expanded access program.
This combination is the treatment of choice for
chronic hepatitis C and has produced overall sustained virological response
(SVR) rates of 54% to 63% in treatment-naïve patients in large phase 3
registration studies (Manns 2001, Fried 2002, Hadziyannis 2004), Dr. Lee and
colleagues noted in their abstract. However, HALT-C Among nonresponders to
previous treatment, the SVR rate is lower (18%, Shiffman 2004), they note.
The trial included 2,702 Canadian adults with chronic hepatitis
C, quantifiable serum HCV RNA levels, and compensated liver disease.
The protocol-defined dose of ribavirin was 800 mg/d in
the first stage of the expanded access program (EAP-1) and 1000/1200 mg/d in
the second stage (EAP-2), Dr. Lee said in a presentation on April 12th.
Results showed that in EAP-2, the SVR rate in
treatment- naïve, genotype 1 patients with normal ALT levels at baseline was
higher than that in the overall group of treatment- naïve, genotype 1 patients
(59% versus 51%).
SVR rates in treatment-naïve genotype 1 patients were
similar in patients with fibrosis scores of F0 (58%), F1 (57%), and F2 (59%)
but decreased progressively in patients with fibrosis scores of F3 (49%) and F4
(43%). "Thus, more aggressive and prolonged therapy may be needed to
increase SVR rates in patients with advanced fibrosis," Dr. Lee commented.
Among previously treated patients, SVR rates were
higher in relapsers than non-responders and in patients who had received prior
interferon monotherapy rather than combination therapy. Thus, retreatment is a
valid option for such patients, Dr. Lee said.
He concluded that the results in the study's diverse
population are in line with those observed with the same treatment regimens in
large phase 3 trials. Importantly, the diverse cohort, he said, represents
populations encountered in a typical clinical practice unlike clinical trials
which tend to include a highly selective cohort.
[Presentation title: Management of Chronic Hepatitis C
in a Diverse Population With Peginterferon Alfa-2A and Ribavirin: Final Results
of the Canadian Pegasys Expanded Access Program. Abstract Number 615]
http://www.therapeuticsdaily.com
SAN DIEGO, and SEOUL, South
Korea, April 13 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. and LG
Life Sciences, Ltd., presented data from an in vitro study showing that ANA380
(LB80380) retains potency against multiple mutant strains of hepatitis B virus
(HBV) which are resistant to lamivudine, adefovir, entecavir or telbivudine,
during a poster presentation at the 42nd Annual Meeting of the European
Association for the Study of the Liver (EASL) in Barcelona, Spain, today at
1:00 p.m. CEST (7:00 a.m. EDT).
The study found that the in
vitro antiviral potency of ANA380 against seven of nine mutants that were
resistant to lamivudine, adefovir, entecavir or telbivudine was not
significantly different from the antiviral potency against wild type HBV,
indicated by a less than or equal to 2-fold difference in EC50, a measure of
inhibition of virus replication. In addition, two HBV mutants that have been
associated with clinical failure to entecavir or telbivudine, respectively,
showed only small decreases (5 and 7 fold, respectively) in sensitivity to
ANA380's antiviral effects in vitro. ANA380 was active against the HBV mutant
resistant to telbivudine in prior clinical studies.
"This study illustrates
the promising spectrum of antiviral activity for ANA380 against a defined panel
of genetically defined drug-resistant HBV variants," said Dr. Stephen
Locarnini, M.D., Ph.D., Head, Research & Molecular Development of the
Victorian Infectious Diseases Research Laboratory in Melbourne, Australia.
"This study also suggests
that ANA380/LB80380 may have clinical utility not only in drug-naïve patients
but also in patients who have become resistant to the most commonly used HBV
therapeutic agents," said Lawrence C. Fritz, Ph.D., president and chief
executive officer of Anadys Pharmaceuticals. "Based on these data, we
believe that it is possible that ANA380/LB80380 used in combination with these
existing drugs may help prevent the emergence of resistance. These new results
are also consistent with previously reported clinical data showing that ANA380
is active in patients refractory to lamivudine."
"Clearly, we are
encouraged by these study results and believe they support additional clinical
evaluation to confirm the potential broad clinical utility of ANA380 in
treating patients with chronic HBV infection," said In-Chull Kim, Ph.D.,
President and Chief Executive Officer of LG Life Sciences.
Anadys and LG Life Sciences entered
into a Joint Development and License Agreement in April 2004 providing for the
global development of ANA380 and pursuant to which Anadys acquired
commercialization rights to ANA380 in North America, Europe, Japan and the rest
of the world other than China, Korea, India and countries in Southeast Asia.
Next steps for the program, including a proposed Phase IIb dose selection
clinical trial, are under discussion between Anadys and LGLS.
Study Methods
HBV mutant strains were
generated from a wild-type strain of HBV genotype D through site-directed
mutagenesis. Mutant strains encoded polymerases resistant to lamivudine,
adefovir, entecavir or telbivudine. Replicate HepG2 cell cultures were infected
with HBV DNA using baculovirus vectors and were exposed to different
concentrations of each drug for seven days. Viral DNA then was extracted and
quantified. EC50 values, which were calculated from averages of three
independent experiments, were used to evaluate susceptibility.
Clinical Background
ANA380 is an oral prodrug of
ANA317 (LB80317), a nucleotide analog. Data from 62 HBV infected patients from
a previous Phase II study showed that patients treated daily with ANA380 at 90
mg, 150 mg and 240 mg dose levels experienced reduction in plasma HBV viral DNA
at 12 weeks of 3.9 log10, 3.9 log10 and 4.1 log10 units, respectively, (greater
than 99.9% clearance of the virus in plasma).
ANA380 (LB80380)
ANA380 is a small-molecule
orally available inhibitor of the HBV polymerase. The HBV polymerase is the
enzyme that catalyzes the production of new RNA from the existing strand of
RNA. ANA380 is believed to inhibit viral proliferation by interrupting the
replicating machinery of the virus.
Hepatitis B Virus
HBV is a significant global
health problem that can cause both acute and chronic viral infections.
According to the WHO, of the 2 billion people who have been infected with HBV,
more than 350 million have chronic (lifelong) infections. These chronically
infected persons are at high risk of death from cirrhosis of the liver and
liver cancer, diseases that kill about one million persons each year.
Approximately 1.3 to 1.5 million people worldwide die each year from chronic
HBV and/or related conditions. According to the WHO, HBV is the 10th leading
cause of death each year worldwide. In the U.S., an estimated 5,000 people with
HBV-liver disease die annually. Based on industry analyst reports and available
market data, we estimate that current annual sales of HBV therapies are
approximately $500 million and will exceed $1 billion by 2010. This market
expansion is expected to result from an increasing number of patients receiving
treatment and new therapies that provide greater efficacy and treatment
durability.
About Anadys
Anadys Pharmaceuticals, Inc., http://www.anadyspharma.com/ , is a
biopharmaceutical company committed to advancing patient care by discovering,
developing and commercializing novel small molecule medicines for the treatment
of viral diseases and cancer. The Company's programs focus on Toll-Like
Receptor-based small molecule product candidates and direct antiviral compounds
that inhibit key steps in viral proliferation. The Company has core expertise
in medicinal chemistry coupled with structure-based drug design, and is
developing compounds for the treatment of hepatitis C infection, hepatitis B
infection and cancer.
About LG Life Sciences
LG Life Sciences, Ltd.
("LGLS") is the leading pharmaceutical company based in South Korea,
committed to promoting health and well-being of patients. Its key therapeutic
areas include metabolic and cardiovascular diseases as well as infectious and
liver diseases. LGLS seeks to continue developing global brand products, such
as Factive(R) (gemifloxacin), and expanding its market presence in the world
with focus in Asia. Additional information is available on its corporate
website, http://www.lgls.com/ .
Safe Harbor Statement
Statements in this press
release that are not strictly historical in nature constitute
"forward-looking statements." Such statements include, but are not
limited to, references to the believed potential spectrum of activity of
ANA380/LB80380 against a defined panel of genetically defined drug-resistant
HBV variants, the possibility that ANA380/LB80380 will have clinical utility
not only in drug-naïve patients but also in patients who have become resistant
to the most commonly used HBV therapeutic agents, the possibility that
ANA380/LB80380 used in combination with existing drugs could help prevent the
emergence of resistance, future development activities for ANA380/LB80380, and
statements regarding the projected future market expansion for HBV therapies.
Such forward-looking statements involve known and unknown risks, uncertainties
and other factors, which may cause Anadys' actual results to be materially
different from historical results or from any results expressed or implied by
such forward-looking statements. In particular, the results of in vitro studies
and initial clinical trials may not be predictive of future results, and Anadys
cannot provide any assurances that any of its product candidates will not have
unforeseen safety issues, will have favorable results in future clinical trials
or will receive regulatory approval. In addition, future activities around
ANA380/LB80380 are currently under discussion between LG Life Sciences and
Anadys and there is no guarantee that the parties will be able to agree to a
global development plan or next steps for the program. Furthermore, Anadys'
results may be affected by risks related to its collaborative relationships
with Novartis and LG Life Sciences, competition from other biotechnology and
pharmaceutical companies, its effectiveness at managing its financial resources,
its ability to successfully develop and market products, the level of effort
that its collaborative partners devote to development and commercialization of
its product candidates, difficulties or delays in its pre-clinical studies or
clinical trials, difficulties or delays in manufacturing its clinical trials
materials, the scope and validity of patent protection for its products,
regulatory developments involving future products and its ability to obtain
additional funding to support its operations. Risk factors that may cause
actual results to differ are more fully discussed in Anadys' SEC filings,
including Anadys' Form 10-K for the year ended December 31, 2006. All
forward-looking statements are qualified in their entirety by this cautionary
statement. Anadys is providing this information as of this date and does not
undertake any obligation to update any forward-looking statements contained in
this document as a result of new information, future events or otherwise.
Anadys Pharmaceuticals, Inc.
CONTACT:
Vince Reardon, Sr. Director,
Investor Relations, Investor
Relations & Corporate
Communications of Anadys Pharmaceuticals, Inc.,
+1-858-530-3653, vreardon@anadyspharma.com ;
or
Ki Seok Kim, General Manager,
Investor Relations of LG Life
Sciences, Ltd., +82-2-3773-0619,
Web site: http://www.lgls.com/
Web site: http://www.anadyspharma.com/