Pharmos
Initiates US Enrollment in Phase III Study of Dexanabinol
For Traumatic Brain Injury
Drug
Holds Promise to be First TBI Therapeutic Treatment
ISELIN, N.J., July 1 -- Pharmos Corporation (Nasdaq:
PARS and Nasdaq Europe: PHRM) announced today that U.S.
enrollment has commenced in its Phase III study of dexanabinol
for traumatic brain injury (TBI), ongoing in over 60 international
centers where more than 630 patients have been enrolled
to date. A total of up to fifteen U.S. trauma centers
are expected to be active in the pivotal study, in which
total patient enrollment is expected to be completed around
yearend. Positive data from the study could enable Pharmos
to submit an NDA to the FDA requesting marketing approval
in the U.S. as the first therapeutic treatment for TBI.
The world market for the product is estimated at over
$1 billion annually.
The
first patient in the U.S. was enrolled at Penn State Milton
S. Hershey Medical Center in Hershey, Pennsylvania. The
trial at that location is under the direction of Principal
Investigator Kevin Cockroft, M.D., assistant professor,
Department of Neurosurgery, and Associate Investigator
Jonas Sheehan, M.D., assistant professor, Department of
Neurosurgery. Raj K. Narayan, M.D., Chairman of the American
Brain Injury Consortium (ABIC), Chairman of the Department
of Neurosurgery at University of Cincinnati and a member
of the dexanabinol study safety committee said, "Neurosurgeons
and their patients as well as all other emergency medical
personnel are in serious need of an effective medication
that can protect the brain from severe damage in injured
patients and thereby improve neurological outcome. The
principal investigators participating in this study are
very enthusiastic about having a product available to
treat this significant problem. The initiation of patient
enrollment in this trial may also raise public awareness
over the magnitude and devastating impact of brain injury,
thereby lending a voice to what has been referred to as
a silent epidemic."
The
expansion of the study to the U.S. follows FDA authorization
of Pharmos' Investigational New Drug application. All
of the U.S. centers are following the same protocol used
internationally and will comply with ABIC procedural guidelines
in clinical head injury trials. "We are happy to
join efforts with our U.S. colleagues in the development
of a product that is needed all over the world,"
said Dr. Graham Michael Teasdale, Chairman of the European
Brain Injury Consortium (EBIC).
Haim
Aviv, Ph.D., Pharmos Chairman and CEO, said, "Our
goal in this trial -- to prove a significant clinical
benefit for TBI patients -- is backed by favorable Phase
I and II clinical data and solid results from our extensive
research into the unique mechanism of action displayed
by this compound. If this drug is successful, it will
be the only approved drug to treat this condition and
will represent a substantial commercial opportunity for
Pharmos."
About
TBI
TBI
is a leading cause of death and disability in industrialized
societies. Annually within the U.S. there are about 1.5
million head injuries, roughly 300,000 hospital admissions
for head trauma, nearly 52,000 deaths and approximately
80,000 cases of severe long-term disability. The annual
cost of acute care and rehabilitation in the U.S. for
new cases is estimated to be as high as $10 billion. At
present, there are an estimated 5.3 million Americans
living with disabilities resulting from TBI. The annual
market potential for the first FDA-approved drug treating
TBI victims in the U.S. is estimated to be over $500 million.
The worldwide market potential may exceed $1 billion.
The
incidence of TBI is highest among young men as victims
of automobile accidents and the elderly who are prone
to falls. TBI occurs in two stages, the first of which
is characterized by the initial impact on, or rapid internal
shifting of, the brain, resulting in skull fractures and
bruising. Without treatment, these primary effects trigger
secondary processes in which neurotoxic chemicals are
released in the brain and destroy healthy cells. Dangerous
inflammatory processes may also develop, ultimately causing
the most severe and long-lasting damage suffered by those
who survive. Current therapy is limited to emergency medical
and rehabilitative care, leaving TBI victims a totally
unserved market globally.
About
Dexanabinol
Dexanabinol
possesses several characteristics that make it an ideal
candidate to treat TBI, and the trial has been designed
to prove the clinical benefits of this unique molecule.
First, dexanabinol appears to have a relatively long therapeutic
window that may result from its unique combination of
certain potent neuro-protective mechanisms that work at
different intervals from the time of insult. Second, toxicological
studies and Phase I and Phase II clinical trials demonstrated
dexanabinol to be safe and well tolerated in animals and
in healthy and sick patients. Third, in Phase II clinical
development, dexanabinol demonstrated significant efficacy
in preventing the elevation of intracranial pressure and
in orientation and memory, and a trend toward efficacy
in the primary neurological outcome. Pharmos notes that
its clinical protocol strongly adheres to and reflects
all its pre-clinical and clinical findings.
Dexanabinol's
neuro-protective properties result from its unique combination
of three critical mechanisms of action. Dexanabinol is
an anti- inflammatory compound that may block the synthesis
of pro-inflammatory cytokines in the injured brain, significantly
slowing the breakdown of the blood-brain barrier and cellular
death via apoptosis and necrosis. It is also an NMDA antagonist
that prevents the lethal massive influx of calcium ions
into the cells of the injured brain. Finally, the compound
works as an anti- oxidant, acting to protect the brain
by scavenging free radicals that are formed when the brain
sustains an injury. Dexanabinol is the only compound possessing
these multiple mechanisms of action that has been tested
in the treatment of TBI.
About
the Trial
The
purpose of the pivotal Phase III study is to determine
the safety and efficacy of dexanabinol in severe TBI patients.
Total enrollment of approximately 900 multinational severe
TBI patients is now expected in the double blind, randomized,
placebo controlled trial, representing a small increase
from the original estimate. To date more than 630 patients
have been enrolled in over 60 participating trauma centers
in Europe, Israel, Australia and the U.S. The primary
endpoint for the study will be patient outcome as measured
on the Glasgow Outcome Scale - Extended (GOSE) six months
after injury. In order to maximize the opportunity to
measure a drug effect with statistical significance, enrollment
of patients into the study is carefully controlled by
a series of detailed, rigid inclusion and exclusion criteria.
Patients
enrolled in the study are given a single dose of 150mg
dexanabinol or (placebo) vehicle within six hours after
injury. Standard care is provided to all patients consistent
with protocols developed by ABIC and EBIC. Intracranial
pressure is monitored until stabilized at a medically
acceptable level. Patients are evaluated at three and
six months according to GOSE. The goal of the study is
to observe at six months a statistically meaningful difference
in outcome in the number of dexanabinol-treated victims
as compared to the placebo group.
About
Pharmos
Pharmos
discovers, develops, and commercializes novel therapeutics
to treat a range of indications, in particular neurological
and inflammation- based disorders. The Company's first
neuroprotective product is dexanabinol, a tricyclic dextrocannabinoid,
currently undergoing clinical testing as a treatment for
TBI and as a preventive agent against post-surgical cognitive
impairment. Other dextrocannabinoid compounds and selective
CB2 receptor agonist compounds from Pharmos' proprietary
synthetic cannabinoid library are being studied in pre-clinical
programs targeting, pain, multiple sclerosis and other
disorders.
Statements
made in this press release related to the business outlook
and future financial performance of the Company, to the
prospective market penetration of its drug products, to
the development and commercialization of the Company's
pipeline products and to the Company's expectations in
connection with any future event, condition, performance
or other matter, are forward-looking and are made pursuant
to the safe harbor provisions of the Securities Litigation
Reform Act of 1995. Such statements involve risks and
uncertainties which may cause results to differ materially
from those set forth in these statements. Additional economic,
competitive, governmental, technological, marketing and
other factors identified in Pharmos' filings with the
Securities and Exchange Commission could affect such results.
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