First IND Filing for a Product to Treat Anthrax Toxin
ANNAPOLIS, Md., March 31 /PRNewswire/ -- PharmAthene, Inc. today announced
that it has filed an Investigational New Drug (IND) application with the U.S.
Food and Drug Administration to initiate human clinical trials of ToxBlox(TM).
ToxBlox(TM), a novel protein initially known as Dominant Negative Inhibitor
(DNI), is being developed as a potent therapeutic agent to combat the lethal
effects of anthrax toxin.
PharmAthene plans to initiate a Phase I placebo-controlled, dose
escalation clinical trial to evaluate the safety, tolerability and
pharmacokinetics of ToxBlox(TM) in healthy adult volunteers. Submission of
this IND by PharmAthene is the first step in the process of obtaining approval
for ToxBlox(TM) as a treatment for inhalational anthrax in the event of a
bioterrorism attack.
"Through its agreements with Harvard Medical School, DARPA, and the US
Army Medical Research and Materiel Command, PharmAthene has made significant
strides in meeting our Nation's urgent biosecurity need for a therapeutic
anthrax antitoxin," said David P. Wright, President & CEO. "Today's
announcement recognizes PharmAthene's successful regulatory, preclinical and
manufacturing strategy, which relies upon both proven internal expertise in
drug development and project outsourcing. It highlights the impact and
extraordinary progress we have made in a very short period of time."
In addition to filing an IND, PharmAthene has completed process
development activities in the ToxBlox(TM) manufacturing process. The company
is now producing commercial quantities of ToxBlox(TM) in compliance with Good
Manufacturing Practice (GMP) regulations. Typically, this would not occur
until later in the drug development process, however, PharmAthene has embraced
an aggressive manufacturing strategy to ensure the availability of GMP product
as early as possible. Consequently, should an emergency occur prior to FDA
approval of ToxBlox(TM), PharmAthene will be well-positioned to work with the
appropriate governmental agencies, including the FDA, to make ToxBlox(TM)
available for emergency use.
ToxBlox(TM) (Dominant Negative Inhibitor, DNI) is a mutated anthrax
protective antigen (PA) that acts as a therapeutic agent to prevent release of
anthrax toxins into the cell, thus completely blocking the deleterious effects
of the toxins. As a result, ToxBlox(TM) is being developed as a treatment for
hospitalized patients with anthrax infection.
ToxBlox(TM) has been shown to be effective in treating and blocking the
toxic effects associated with anthrax infection in rat and rabbit animal
models. In a recently completed study in which rabbits were challenged
subcutaneously with a massive anthrax spore load, ToxBlox(TM) was demonstrated
to be highly protective. Three groups of 6 rabbits all received 7000 times
the median lethal dose (LD50) of B. anthracis spores. Following spore
challenge, animals were either untreated (control group) or were treated with
ToxBlox(TM) (low dose and high dose groups). On day 4 following challenge, 0%
(0/6) of the animals in the control group were alive compared to 50% (3/6)
survival in the low dose group and 100% survival in the high dose ToxBlox(TM)
group. Prior to stopping ToxBlox(TM) on Day 5, 2 additional animals in the
low dose group and 1 animal in the high dose group died. The remaining
animals in the high dose group (5/6) are currently being followed and remain
alive at Day 30 post-challenge (Day 25 after stopping ToxBlox(TM)).
The survival seen to date in the ToxBlox(TM) high-dose group is
unprecedented in that the animals received an enormous spore challenge dose
(7000 x LD50) and a very short duration of therapy (5 days). Prior studies in
rhesus monkeys challenged with 8 times the LD50 have shown that antibiotics
administered for 30 days are effective; however, when the antibiotics were
stopped after 30 days, death due to anthrax occurred in some animals.
PharmAthene's Chief Scientific Officer, Dr. Sol Langermann said, "We are
extremely encouraged by the results of this spore challenge study. The
ongoing survival of the animals in the high dose group following the
withdrawal of ToxBlox(TM) is particularly intriguing. Prior studies have
shown that spores can remain active for several weeks following challenge,
thus leading to the recommendation that patients exposed to anthrax receive
antibiotics for up to 60 days following exposure. No antibiotics were used in
this study; therefore, we anticipated that animals might be at risk of further
toxin exposure and death after ToxBlox(TM) was discontinued. Clearly, this
has not occurred and further studies to better understand the full spectrum of
ToxBlox(TM) activity are planned."
The initial research on DNI, conducted by Harvard Medical School
researchers, was funded through a grant to Harvard from the National Institute
for Allergy & Infectious Disease (NIAID), a division of the National
Institutes of Health (NIH). Critical follow-on funding and support to
PharmAthene from the Defense Advanced Research Projects Agency (DARPA) and the
U.S. Army Medical Research and Materiel Command (MRMC) allowed for rapid
development of ToxBlox(TM). "We are grateful for this level of support from
the various departments of the U.S. Government and their acute recognition of
the need for advanced technology for detection, diagnostics, communications,
post-exposure prophylaxis, vaccines, treatment; including better antibiotics,
monoclonal antibodies and antitoxins as well as new methods of
decontamination," said David Wright. "These activities are a testament to the
extraordinary effort being made to insure the safety of all Americans against
another potential bioterrorism attack with B. anthracis."
About PharmAthene
PharmAthene, Inc., a privately-held corporation, was formed in March, 2001
by Drs. John Collier, Stephen Lory and John Mekalanos of Harvard Medical
School, John Young of the Salk Institute for Biological Studies, and Mr. Joel
McCleary, a private investor who is serving as Chairman of the Board. The
Company was formed to address the urgent biosecurity needs of this Nation and
is committed to rapid development of important and novel biotherapeutics. For
more information about the Company, please visit http://www.PharmAthene.com.
FORWARD LOOKING STATEMENT
Statements included within this press release that are not historical in
nature constitute forward-looking statements for the purposes of the safe
harbor provided by the Private Securities Litigation Reform Act of 1995.
Readers can identify these statements by the fact that they do not relate
strictly to historical or current facts and use words such as "anticipates,"
"believes," "continue," "estimates," "expects," "intends," "may," "will" and
other similar words or terms in connection with a discussion of PharmAthene's
plans and objectives for future operations or financial performance. Such
statements speak only as of the date the statement was made, and PharmAthene
undertakes no obligation to publicly update or revise any forward-looking
statements, whether as a result of new information, future events, or
otherwise. Readers are cautioned that forward-looking statements are
inherently subject to risks or uncertainties, some of which cannot be
predicted or quantified. Future events and actual results could differ
materially from those set forth in, contemplated by, or underlying the
forward-looking statements. The risks and uncertainties to which forward-
looking statements are subject include, but are not limited to, the effect of
acceptance of the PharmAthene's products by the marketplace, competition, and
other risks. There can be no assurance that PharmAthene's development efforts
will succeed, that any products developed will receive required regulatory
clearance or that, even if such regulatory clearance were received, such
products would ultimately achieve commercial success.
SOURCE PharmAthene, Inc.
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Related links:
http://www.PharmAthene.com
CONTACT:
Mark Cooke, Sr. Director Education, of
PharmAthene, Inc., +1-410-571-8920, or cookem@pharmathene.com
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