Pharmos
Dosing Patients in Second Brain Protection Indication
for Dexanabinol
Iselin
NJ, April 8, 2003 - Pharmos Corporation (Nasdaq: PARS
and Nasdaq Europe: PHRM) announced today it has begun
dosing patients in a Phase IIa feasibility and safety
study to determine the effectiveness of dexanabinol in
reducing post-surgical cognitive impairment (CI). No approved
medication is currently available to prevent the onset
of CI, a condition that occurs in a significant percentage
of patients undergoing coronary artery bypass grafting
(CABG) under cardiopulmonary bypass (CS-CPB) surgery.
Pharmos is simultaneously testing the effectiveness of
dexanabinol as a neuroprotective treatment for traumatic
brain injury (TBI) in an international Phase III study,
patient enrollment for which is expected to be completed
in 2003.
"Data
from preclinical and clinical testing of dexanabinol have
shown the compound to have powerful anti-inflammatory
and neuroprotective properties in the brain, all of which
are critical in preventing cell death associated with
ischemic conditions common to many central nervous system
disorders," said Haim Aviv, Ph.D., Pharmos Chairman
and CEO. "The multiple mechanisms of action inherent
in dexanabinol and in proprietary derivative compounds
are unique. Pharmos intends to exploit this advantage
commercially by targeting appropriate therapeutic areas
that represent significant market opportunities, such
as TBI and post-surgical CI prevention."
Clinical
evidence of dexanabinol's therapeutic potential in preventing
CI was demonstrated in Pharmos' Phase II TBI trial, completed
in 2000. As an important secondary outcome of the Phase
II TBI trial, patients treated with dexanabinol showed
statistically significant improvement in cognition and
orientation as measured by the Galveston Orientation and
Amnesia Test at three and six months after injury, compared
to placebo. In preclinical findings, dexanabinol was an
effective neuroprotectant in animal models of focal brain
ischemia demonstrating robust sparing of hippocampal cells
pivotal to cognition.
Cognitive
decline may develop following CS-CPB as a result of microemboli-triggered
ischemic events and related inflammatory processes. For
certain subsets of patients, the risk of cognitive impairment
is significant, compromising recovery and adding to rehabilitation
costs. Development of post-surgical CI also increases
the risk of developing future dementia.
About
Post-Surgical CI
Each year over one million patients worldwide undergo
CS-CPB operations(1). In the United
States, over 350,000 coronary artery bypass surgeries
are performed each year(2), making
it the most frequent major surgical procedure performed
in hospitals. As mortality from these surgeries has fallen
in recent years, medical attention has increasingly focused
on morbidities associated with coronary surgeries, especially
impairment of cognitive function experienced by a high
percentage of these patients. Certain studies show that
eight days after surgery as many as 50% of the patients
may suffer cognitive defects(3),
such as inability to concentrate, memory loss, a slowdown
in response and difficulty in returning to pre-surgical
functioning. Importantly, even after 12 months, cognitive
deficits persist as a source of disability in as many
as 30% of the patients(4). Recent
long term longitudinal studies indicate that a significant
proportion of patients may continue to deteriorate over
time, with cognitive deficits continuing up to five years
after surgery . Age and other factors, such as diabetes,
affect the frequency of CI.
About
the Trial
The trial is underway at three leading medical centers
in Israel. The exploratory, Phase IIa, double-blind, placebo-controlled
trial will enroll up to 200 patients undergoing CS-CPB.
Patients are being randomized one-to-one to receive a
single dose of either 150 mg. dexanabinol or placebo prior
to initiation of CPB. Each patient will be evaluated prior
to surgery, at discharge, at six weeks, and at three months
following surgery to assess the incidence and degree of
post-surgical CI. The degree of cognitive impairment will
be assessed using a sophisticated and validated battery
of computerized neuropsychological tests including attention
deficit, memory loss and speed of reaction. Among other
inclusion/exclusion criteria, patients included in the
study will be age 60 or older who are candidates for elective
CS-CBP and who do not show signs of CI or dementia according
to the DSM-IV (Diagnostic Statistical Manual, version
IV) criteria for dementia, and scoring on the Mini Mental
State Examination, prior to surgery.
The
primary efficacy analysis will compare the reduction in
cognitive deficit in the dexanabinol-treated group compared
with the placebo group. The additional neuropsychological
secondary efficacy analyses will serve to evaluate and
compare quality of life and assess additional functional
outcome between the treated and placebo patients. An independent
safety committee will monitor the data on an ongoing basis
to ensure patient safety.
About
Dexanabinol
Dexanabinol is the first neuroprotective compound under
development from Pharmos' library of synthetic tricyclic
dextrocannabinoid compounds. Dextrocannabinoids lack binding
activity in the two known cannabinoid receptors, CB1 and
CB2, and as a result, this family of compounds does not
show the psychotropic effects seen with naturally occurring
cannabinoids. Drug candidates in this family have three
main actions: they block the activation of specific ion
channels in nerve cells by binding to NMDA receptors as
non-competitive antagonists, inhibit inflammatory mechanisms,
and operate as antioxidants. These three properties enable
dextrocannabinoids to reduce necrosis and apoptosis caused
by brain trauma, ischemia and a range of neurodegenerative
disorders. The Company's focus on dexanabinol and derivative
compounds is wide ranging, and a number of dextrocannabinoid
compounds are being evaluated in preclinical models for
a variety of indications.
About
Pharmos
Pharmos discovers, develops, and commercializes novel
therapeutics to treat a range of neurological disorders
such as traumatic brain injury, post-surgical mild cognitive
impairment, stroke, pain, multiple sclerosis, and other
CNS and peripheral neuro-inflammatory indications.
(1)Efthimiadis
A, Lefkos N, Psirropoulos d, et al. Risk factors of ischaemic
heart disease and long-term outcome after coronary bypass
surgery. J Cardiovasc Surg (Torino) (Italy), Dec 2001,
42(6) p 731-4
(2)Erickson LC, Torchiana DF, Schneider
EC, et al. The relationship between managed care insurance
and use of lower-mortality hospitals for CABG surgery.
JAMA 2000 Apr 19;283(15):1976-82
(3)Grieco G, d'Hollosy M, Culliford
AT, et al. Evaluating neuroprotective agents for clinical
anti-ischemic benefit using neurological and neuropsychological
changes after cardiac surgery under cardiopulmonary bypass.
Stroke 1996;27:858-874
(4)Newman SP, Klinger L, Venn GE,
et al. The persistence of neuropsychological deficits
twelve months after coronary artery bypass surgery. In:
Willner AE, Rodewald G, eds. Impact of Cardiac Surgery
on the Quality of Life. New York, NY: Plenum Press; 1990:173-179
(5)Newman et al. Longitudinal Assessment
of Neuroprotective Function After Coronary Artery Bypass
Surgery. N Engl Med 2001:395-402
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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