Anthrax Monoclonal Antibody Valortim(TM) Demonstrates Therapeutic Effect in New Primate Model of Established Anthrax Infection
March 30 2007 - 11:00AM
PR Newswire (US)
Pilot Study Demonstrates 50% Survival in Valortim-Treated Animals
PRINCETON, N.J., and ANNAPOLIS, Md., March 30
/PRNewswire-FirstCall/ -- Medarex, Inc., 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.
Findings of preclinical studies describing the activity of Valortim
against anthrax infection were published in the October 2006 issue
of the journal Infection and Immunity. An article abstract is
available on the journal web site at
http://iai.asm.org/cgi/content/abstract/74/10/5840. 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
http://www.pharmathene.com/. In January 2007, PharmAthene announced
that it had signed a definitive merger agreement with Healthcare
Acquisition Corp. (AMEX:HAQ). HAQ has filed with the Securities and
Exchange Commission a preliminary proxy statement in connection
with the proposed merger transaction involving PharmAthene. HAQ AND
ITS DIRECTORS AND EXECUTIVE OFFICERS AS WELL AS PHARMATHENE AND ITS
DIRECTORS AND EXECUTIVE OFFICERS MAY BE DEEMED TO BE PARTICIPANTS
IN THE SOLICIATION OF PROXIES FOR THE SPECIAL MEETING OF HAQ'S
STOCKHOLDERS TO BE HELD TO APPROVE THE PROPOSED MERGER.
SECURITYHOLDERS AND OTHER INTERESTED PERSONS ARE URGED TO READ THE
PRELIMINARY PROXY STATEMENT REGARDING THE PROPOSED MERGER FILED
WITH THE SECURITIES AND EXCHANGE COMMISSION ON FEBRUARY 9, 2007 AND
THE AMENDMENTS THEREOF AND THE DEFINITIVE PROXY STATEMENT AS SUCH
DOCUMENTS BECOME AVAILABLE AS THEY WILL CONTAIN IMPORTANT
INFORMATION ABOUT THE PROPOSED MERGER. HAQ'S DEFINITIVE PROXY
STATEMENT, WHEN AVAILABLE, WILL BE MAILED TO HAQ'S STOCKHOLDERS AS
OF A RECORD DATE TO BE ESTABLISHED FOR VOTING ON THE PROPOSED
MERGER. STOCKHOLDERS WILL ALSO BE ABLE TO OBTAIN A COPY OF THE
DEFINITIVE PROXY STATEMENT, WITHOUT CHARGE, BY DIRECTING A REQUEST
TO HAQ AT: 2116 FINANCIAL CENTER, 666 WALNUT STREET, DES MOINES,
IOWA 50309. THE PRELIMINARY PROXY STATEMENT AND DEFINITIVE PROXY
STATEMENT, ONCE AVAILABLE, AND THE FINAL PROSPECTUS AND OTHER SEC
FILINGS OF HAQ CAN ALSO BE OBTAINED, WITHOUT CHARGE, AT THE
SECURITIES AND EXCHANGE COMMISSION'S INTERNET SITE
(http://www.sec.gov/). HAQ AND PHARMATHENE CLAIM THE PROTECTION OF
THE SAFE HARBOR FOR "FORWARD- LOOKING STATEMENTS" WITHIN THE
MEANING OF THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995.
FORWARD-LOOKING STATEMENTS ARE STATEMENTS THAT ARE NOT HISTORICAL
FACTS. SUCH FORWARD-LOOKING STATEMENTS, BASED UPON THE CURRENT
BELIEFS AND EXPECTATIONS OF MANAGEMENT OF HAQ AND PHARMATHENE
REGARDING, AMONG OTHER THINGS, THE BUSINESS OF PHARMATHENE AND THE
MERGER, ARE SUBJECT TO RISKS AND UNCERTAINTIES, WHICH COULD CAUSE
ACTUAL RESULTS TO DIFFER FROM THE FORWARD-LOOKING STATEMENTS. 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 http://www.medarex.com/. 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. NOTE: 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. DATASOURCE: Medarex, Inc. and PharmAthene,
Inc. CONTACT: Laura S. Choi, Investor Relations, +1-609-430-2880,
ext. 2216; or Jean Mantuano, Corporate Communications,
+1-609-430-2880, ext. 2221, both of Medarex, Inc.; or Stacey
Jurchison, Director, Corporate Communications, PharmAthene, Inc.,
+1-410-571-8925, Web site: http://www.pharmathene.com/
http://www.medarex.com/
Copyright
Healthcare Acquisition (AMEX:HAQ)
Historical Stock Chart
From Aug 2024 to Sep 2024
Healthcare Acquisition (AMEX:HAQ)
Historical Stock Chart
From Sep 2023 to Sep 2024