Medarex, Inc. (Nasdaq: MEDX), a leading monoclonal antibody company, and
PharmAthene, Inc., a privately held biotechnology company dedicated to the
development of biodefense countermeasures, today announced that
Valortim(TM), a fully human monoclonal antibody product candidate being
developed for the prevention and treatment of anthrax infection, has been
shown to have a therapeutic effect in a new primate model of established
inhalation anthrax infection.
The new model, which is being developed at the United States Army
Medical Research Institute of Infectious Diseases (USAMRIID), seeks to
improve on existing therapeutic models for anthrax by closely monitoring
the disease process to establish the presence of anthrax bacteremia and
determine the optimal window for therapeutic intervention. In addition, the
new model uses the African Green monkey, which, based on research data,
USAMRIID believes follows a similar disease course as is expected in humans
exposed to aerosolized Bacillus anthracis spores. B. anthracis is the
bacterium responsible for anthrax infection. This new animal model has not
yet been validated under the U.S. Food and Drug Administration Animal
Effectiveness Rule.
In the pilot study conducted at USAMRIID, adult African Green monkeys
were exposed to aerosolized anthrax spores and blood samples were collected
at regular intervals beginning 24 hours post-exposure. The samples were
closely monitored for evidence of bacteremia both by culture and by use of
a rapid assay designed to detect protective antigen. Protective antigen is
one of the toxins produced by B. anthracis and its presence in the blood is
being evaluated as a surrogate marker for symptomatic anthrax disease. Once
bacteremia was detected by the rapid assay, animals were administered
either Valortim or saline (control) by intravenous injection. In the study,
50% of the Valortim-treated animals survived compared to none of the
saline-treated animals.
"While post-exposure models of inhalation anthrax infection are
relatively straight-forward, demonstrating efficacy in a therapeutic model
for inhalation anthrax infection has proven somewhat challenging," remarked
Valerie Riddle, M.D., Vice President and Medical Director for PharmAthene.
"In most animal species in which anthrax has been studied, the disease
course and time to death is markedly shorter than that seen in humans,
making it challenging to evaluate the potential therapeutic efficacy of
promising products. The model being developed by USAMRIID uses a rapidly
detectable surrogate marker for the development of symptomatic disease to
provide a consistent window in which to determine the therapeutic efficacy
of Valortim in animals confirmed to have active disease. We believe this
will be an important consideration for the licensure of novel anthrax
therapeutics under the Food and Drug Administration's proposed Animal
Rule."
Dr. Riddle continued, "This is a very encouraging survival result when
one considers that these animals had bacteria multiplying in their blood
and were poised to manifest severe symptoms and death at the time they were
treated with Valortim. We plan to continue to collaborate with USAMRIID to
further refine the model and determine the optimal therapeutic dose for
Valortim."
"Previous studies in the rabbit animal model had suggested the capacity
of Valortim to successfully treat symptomatic animals," noted Israel Lowy,
M.D., Ph.D., Senior Director of Infectious Disease for Medarex. "The
current studies in a non-human primate model, that may be more relevant to
human disease, provide additional confirmation for those results. The
methodological advances of the group at USAMRIID may help to better define
the therapeutic potency of Valortim and other agents in this challenging
setting."
Preclinical studies suggest that Valortim has the potential to provide
significant protection against anthrax infection when administered
prophylactically (prior to the emergence of symptoms of anthrax infection)
and also may increase survival when administered therapeutically (once
symptoms become evident). In these studies, Valortim has been shown to
protect both rabbits and monkeys against the lethal effects of anthrax
infection when administered at the time of exposure, at doses as low as 1.0
mg/kg. When administered to rabbits after the development of symptoms,
Valortim also improved survival as late as 48 hours post-exposure as
compared to controls.
"We believe that there are distinct characteristics of Valortim that
make it an ideal choice for military and civilian protection against an
anthrax bioterrorist attack," commented David P. Wright, President and
Chief Executive Officer of PharmAthene. "As our Phase I results have
demonstrated, a single intramuscular dose of Valortim produces levels of
antibodies in humans that correspond to protective levels in animal models
and is well tolerated. Based on the impressive human safety and animal
efficacy data collected to date, we believe that Valortim could meet the
needs of the U.S. Government and could ultimately be selected for inclusion
in the Strategic National Stockpile to provide protection to the American
public."
About Valortim
Valortim (MDX-1303) is a fully human antibody designed to protect
against anthrax infection, including inhalation anthrax, the most lethal
form of illness in humans caused by the Bacillus anthracis bacterium. The
investigational antibody is designed to target a protein component known as
the anthrax protective antigen (PA) of the lethal toxin complex produced by
the bacterium. The anthrax protective antigen is believed to initiate the
onset of the illness by attaching to cells in the infected person, and then
is believed to facilitate the entry of additional destructive toxins into
the cells. Valortim is designed to target anthrax protective antigen and
protect the cells from damage by the anthrax toxins.
In preclinical studies, Valortim both protected against infection and
induced recovery and survival in animals exposed to lethal doses of
inhalation anthrax spores. A study in non-human primates has demonstrated
the potency of Valortim in this model using the potentially most
clinically-useful intramuscular route of administration. In this study, the
animals were challenged with a target aerosol dose of 200 times the median
lethal dose of B. anthracis spores; 6 animals received no treatment, 6
animals received 1 mg/kg of Valortim intramuscularly, and 6 animals
received 10 mg/kg of Valortim intramuscularly, all at the time of aerosol
challenge. None of the animals were given antibiotics or other therapies.
All control animals died within one week of the challenge; all treated
animals in both dose groups were reported alive 60 days post-challenge. The
effectiveness of doses even lower than 1.0 mg/kg may be studied in future
preclinical research.
Valortim has also been administered intravenously and intramuscularly
to healthy human volunteers in a completed phase I study, has been shown to
be well tolerated at doses as high as 20 mg/kg (IV), and was not
immunogenic. These study results were presented at the 2006 Infectious
Diseases Society of America Annual Meeting. Pharmacokinetic analysis
suggested that doses as low as 1 mg/kg resulted in circulating levels of
antibody after a month, with a similar potency for neutralizing anthrax
toxin in vitro as was seen with serum obtained from subjects who had been
vaccinated with anthrax vaccine.
About Anthrax
According to the Centers for Disease Control and Prevention, anthrax is
an acute infectious disease caused by the spore-forming bacterium Bacillus
anthracis. Anthrax most commonly occurs in hoofed mammals and can also
infect humans. Symptoms of disease vary depending on how the disease was
contracted, but usually occur within seven days after exposure. The serious
forms of human anthrax are inhalation anthrax, cutaneous anthrax, and
intestinal anthrax. Initial symptoms of inhalation anthrax infection may
resemble a common cold. After several days, the symptoms may progress to
severe breathing problems and shock. Inhalation anthrax is often fatal,
even with the use of antibiotics.
About PharmAthene, Inc.
PharmAthene, a privately-held biotechnology company, was formed to meet
the critical needs of the United States by developing biodefense products.
PharmAthene is dedicated to the rapid development of important and novel
biotherapeutics to address biological pathogens and chemicals that may be
used as weapons of bioterror. PharmAthene's lead programs include
Valortim(TM) for the prevention and treatment of anthrax infection and
Protexia(R) for the prevention and treatment of morbidity and mortality
associated with exposure to chemical nerve agents. For more information on
PharmAthene, please visit PharmAthene.
About Medarex, Inc.
Medarex is a biopharmaceutical company focused on the discovery,
development and potential commercialization of fully human antibody-based
therapeutics to treat life-threatening and debilitating diseases, including
cancer, inflammation, autoimmune disorders and infectious diseases. Medarex
applies its UltiMAb(R) technology and product development and clinical
manufacturing experience to generate, support and potentially commercialize
a broad range of fully human antibody product candidates for itself and its
partners. More than 30 of these therapeutic product candidates derived from
Medarex technology are in human clinical testing or have had INDs submitted
for such trials, with six of the most advanced product candidates currently
in Phase III clinical trials. Medarex is committed to building value by
developing a diverse pipeline of antibody products to address the world's
unmet healthcare needs. For more information about Medarex, visit its
website at medarex.
About USAMRIID
USAMRIID, located at Fort Detrick, Maryland, is the lead medical
research laboratory for the U.S. Biological Defense Research Program, and
plays a key role in national defense and in infectious disease research.
The Institute's mission is to conduct basic and applied research on
biological threats resulting in medical solutions (such as vaccines, drugs
and diagnostics) to protect the warfighter. USAMRIID is a subordinate
laboratory of the U.S. Army Medical Research and Materiel Command.
The information contained in this press release does not necessarily
reflect the position or the policy of the United States government and no
official endorsement should be inferred.
Statement on Cautionary Factors
For Medarex: Except for the historical information presented herein,
matters discussed herein may constitute forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995 that
are subject to certain risks and uncertainties that could cause actual
results to differ materially from any future results, performance or
achievements expressed or implied by such statements. Statements that are
not historical facts, including statements preceded by, followed by, or
that include the words "potential"; "believe"; "anticipate"; "intend";
"plan"; "expect"; "estimate"; "could"; "may"; or similar statements are
forward-looking statements. Medarex disclaims, however, any intent or
obligation to update these forward-looking statements. Risks and
uncertainties include risks associated with product discovery and
development, uncertainties related to the outcome of clinical trials,
slower than expected rates of study subject enrollment, uncertainties
related to scheduling and completing necessary animal experiments to
satisfy the FDA Animal Rule requirements in the few facilities approved to
perform such experiments, unforeseen safety issues resulting from the
handling of Bacillus anthracis, unforeseen safety issues resulting from the
administration of Valortim(TM) (MDX-1303) in human subjects, uncertainties
related to product manufacturing as well as risks detailed from time to
time in Medarex's public disclosure filings with the U.S. Securities and
Exchange Commission (SEC), including its Annual Report on Form 10-K for the
fiscal year ended December 31, 2006. There can be no assurance that such
development efforts will succeed or that other developed products will
receive required regulatory clearance or that, even if such regulatory
clearance were received, such products would ultimately achieve commercial
success. Copies of Medarex's public disclosure filings are available from
its investor relations department.
Medarex(R), the Medarex logo and UltiMAb(R) are registered trademarks
of Medarex, Inc. All rights are reserved. Valortim(TM) is a trademark of
PharmAthene, Inc. All rights are reserved.
Medarex, Inc. and PharmAthene, Inc.
medarex
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