Pharmos
to Start Clinical Trial of Dexanabinol in Heart Surgery
Patients
ISELIN,
N.J., July 25 /PRNewswire-FirstCall -- Pharmos Corporation
(Nasdaq: PARS and Nasdaq Europe: PHRM) announced today
it has received approval from Israel's Ministry of Health
to clinically test dexanabinol as a preventive agent against
the mild cognitive impairment (MCI) that can follow coronary
surgery under cardiopulmonary bypass (CS-CPB) operations.
Patient enrollment in a Phase II study will commence upon
the completion of various logistical preparations. No
approved medication is currently available to prevent
the onset of MCI after CS-CPB, which is among the most
common operations performed in the world.
"The
commencement of this study is an important strategic move
that broadens our pipeline," said Haim Aviv, Ph.D.,
Pharmos Chairman and CEO. "The potential market is
large and currently void of any product. At the same time,
the large, relatively homogeneous patient population and
elective nature of the surgery make the trial a fairly
uncomplicated one for us."
Cognitive
decline may develop following cardiac surgery as a result
of microemboli-triggered ischemic events and related inflammatory
processes. Pharmos' rationale in going forward with the
clinical study lies in the convergence of the etiology
of the indication with the mechanisms of action of dexanabinol
as a neuroprotectant. As an important secondary outcome
of the Company's Phase II traumatic brain injury (TBI)
trial, completed in 2000, patients treated with dexanabinol
showed statistically significant improvement in cognition
and orientation as measured by the Galveston Orientation
and Amnesia Test (GOAT) at one, three and six months,
compared to placebo. The improved outcome of these patients
as measured by GOAT provides clinical evidence of dexanabinol's
therapeutic potential in preventing MCI. In preclinical
findings, dexanabinol was an effective neuroprotectant
in animal models of focal brain ischemia.
"Post-surgical
MCI is a serious risk facing patients who need major heart
surgery," said Seth Kindler, M.D., Medical Director
of Pharmos. "For certain subsets of patients, the
risk of cognitive impairment is significant, compromising
recovery and adding to rehabilitation costs. Development
of post-surgical MCI is also a known risk factor for the
progression to Alzheimer's Disease. Our objective in undertaking
this study is to evaluate safety and to establish a trend
of efficacy with dexanabinol in these patients."
About
Post-Surgical MCI
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(5). As surgical technology advances,
the average age of patients will continue to rise. Age
and other factors, such as diabetes, affect the frequency
of MCI.
About
the Trial
The
trial protocol has been finalized and the investigational
review board at the Tel-Aviv Sourasky Medical Center has
approved commencement of patient enrollment. The exploratory,
Phase IIa, double-blind, placebo-controlled trial will
enroll up to 200 patients undergoing CS-CPB. Patients
will be randomized one-to-one to receive a single dose
of either 150 mg. dexanabinol or placebo 30 to 60 minutes
after the first thoracic incision and prior to initiation
of CPB. Each patient will be evaluated prior to surgery,
at discharge, six weeks, and three months following surgery
to assess the incidence and degree of post-surgical MCI.
Diagnosis of MCI will be based on criteria developed by
the Mayo Clinic Alzheimer's Disease Research Center. The
degree of cognitive impairment will be assessed using
a sophisticated and validated battery of computerized
neuropsychological tests. 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 MCI or dementia according to the
Mayo Clinic Criteria prior to surgery.
The
primary efficacy analysis will compare the incidence of
development of MCI according to the Mayo criteria in the
dexanabinol-treated group with the incidence in 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 a non-competitive
antagonists, inhibit inflammatory mechanisms, and are
also antioxidants. These three properties enable the dextrocannabinoids
to reduce necrosis and apoptosis caused by brain trauma,
ischemia and a range of neurodegenerative disorders. Dexanabinol
is currently undergoing an international Phase III human
study as a treatment for TBI. 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 stroke, neuropathic pain, nociceptive
pain, neurodegenerative disorders, such as Parkinson's
disease, and autoimmune disorders, such as multiple sclerosis,
inflammatory bowel disease and rheumatoid arthritis, among
others.
Pharmos
discovers, develops, and commercializes novel therapeutics
to treat a range of neurological disorders such as traumatic
brain injury, stroke, pain, multiple sclerosis, and other
CNS and peripheral neuro-inflammatory indications.
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.
(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
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