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June 23, 2003
Neurochem reports promising findings from Alzhemed™ Phase II Study for
Alzheimer's Disease.
- Neurochem, Inc. (TSX: NRM) - announced today a preliminary analysis of the data from
its recently completed Phase II clinical trial for the investigational drug candidate,
Alzhemed™, in patients with mild-to-moderate Alzheimer's disease (AD). The study
revealed promising results for both the primary and secondary objectives of the trial.
There were no safety findings of concern in patients treated with Alzhemed™.
The pharmacokinetic profile of Alzhemed™ has been well characterized and it was
detected in the cerebrospinal fluid (CSF) of the patients, suggesting an ability to
cross the blood brain barrier. Patients with the greatest decrease in amyloid protein in
the CSF were all on Alzhemed™. Furthermore, the majority of patients on the highest
dose of Alzhemed™ showed, at the six- month time point of the ongoing open-label
extension study, stable results on cognitive function test (as measured by the
ADAS-Cog *).
"We are extremely pleased with the preliminary results of the Phase II clinical trial
for Alzhemed™. The results on the cognitive function tests (ADAS-Cog) of the AD
patients are encouraging and promising for the future treatment of the disease. These
results are critical in directing the design of the next trial as they indicate, at this
time, a potential for Alzhemed™ to act on amyloid, which is the underlying pathology
of AD," said Denis Garceau, Ph.D., Vice-President of Drug Development at
Neurochem. "The preliminary results of this trial represent encouraging developments
for the scientific community worldwide working on Alzheimer's disease, and we are
planning to publish the results in a peer-reviewed journal," he concluded.
Dr. Paul Aisen, Professor of Neurology and Medicine at Georgetown University Medical
Center said, "The most promising target in AD therapeutics is the amyloid protein.
This investigational drug candidate has been shown in preclinical development to target
amyloid. This Phase II study demonstrates that Alzhemed™ is well tolerated in
individuals with AD, and is able to cross into the brain." Dr. Aisen concluded,
"The findings of the Phase II study are consistent with a favorable influence of
Alzhemed™ on amyloid. The need to study the impact of this investigational agent
on disease progression in a larger clinical trial is clear."
*Alzheimer's Disease Assessment Scale, cognitive subpart (ADAS-Cog)
Study Design and Results
This Phase II clinical trial was a multi-centre, randomized, double-blind, placebo-controlled
and parallel-designed study. A total of 58 patients with mild-to-moderate AD were
randomized to receive either placebo or Alzhemed™ at daily doses of 100 mg, 200 mg
or 300 mg for 12 weeks. Patients who completed the three-month study were invited to
participate in an open-label extension study for an additional nine months. In this
ongoing open label study, all patients receive 300 mg of Alzhemed™ daily.
PRIMARY OBJECTIVES
The primary objectives of this Phase II clinical trial were to evaluate the safety,
tolerability and pharmacokinetics of Alzhemed™ in patients with mild-to-moderate
AD.
Safety and tolerability
There were no safety findings of concern at the three doses tested. The most frequent
adverse events reported on Alzhemed™ were nausea and vomiting and their occurrence
was dose-dependent. These adverse events were usually temporary and mild-to-moderate in
severity. Only three patients (6.7%) experienced an adverse event (i.e. nausea or
weakness/weight loss) that caused them to discontinue taking Alzhemed™.
Pharmacokinetic profile
The pharmacokinetic profile of Alzhemed™ was well characterized in this AD patient
population. The extent of systemic exposure was approximately proportional to the
administered dose. The bioanalysis revealed the presence of Alzhemed™ in the CSF of
AD patients and the levels appeared to be dose-related. This important finding suggests
that Alzhemed™ crosses the blood brain barrier.
SECONDARY OBJECTIVES
Secondary objectives of the study include assessing the effect of Alzhemed™ on
levels of amyloid ß (Aß42) protein (an important biomarker for AD) in the CSF. Tests on
cognitive function (i.e. ADAS-Cog) and a global measure of performance (CDR-SB**) were
also included on an exploratory basis, although the study was neither powered nor
designed to detect clinical improvement in psychometric tests.
** (Clinical Deterioration Scale Sum of Boxes (CDR-SB))
Biomarker
Patients who had a marked decrease of Aß42 (= 50 pg/ml) in the CSF at the three-month
time point were all on Alzhemed™. A reduction as high as 70% was seen in the two
highest dose groups. These results suggest that Alzhemed™ has the ability to act
on Aß42 levels in humans. This reduction is consistent with the previously reported
ability of Alzhemed™ to significantly decrease Aß42 levels in the brain of a
transgenic mouse model of brain amyloid.
Cognitive function and global measure of performance
As expected for a disease-modifying therapeutic approach, there was no difference on
cognitive function or global measure of performance between the placebo and treated groups
after three months.
Interestingly, patients in the 300 mg treatment group, with stable or declining levels of
Aß42 levels in the CSF at three months, and who have continued in the open-label
extension study, showed a stabilization on cognitive function tests(ADAS-Cog) at the
six-month time point. This compares favorably with a 2-3 point deterioration in cognitive
function test scores over the same time period, in published reports of large cohorts of
control patients.***.
Live Web Conference
Neurochem will host a teleconference and web cast at 10:00 A.M., E.T., today, June 23,
2003, to discuss the findings of this Phase II study. To participate in the
teleconference and webcast, please dial 1 888-575-8232 or alternatively 1-416-406-6819
approximately 10 minutes prior to the start of the teleconference AND access Neurochem's
website at
www.neurochem.com.
The dial-in will allow the participants to listen and ask questions, while webcast
will host a visual presentation.
A replay of the web cast will be available on Neurochem's web site one hour following the
conference call. This webcast will include the conference call and the visual
presentation.
About Alzhemed™
Alzhemed™ is an orally administered, small synthetic molecule that has been
specifically designed to modify the course of AD by interfering with the association
between glycosaminoglycans (GAGs) and Aß protein. As part of a "disease modifying"
class of product candidates, Alzhemed™ is expected to act at two levels: in
preventing and stopping the formation and deposit of amyloid fibrils in the brain and in
binding to soluble Aß protein to inhibit the inflammatory response associated
with amyloid build-up in AD. Its anti-amyloid potential has been demonstrated in an
aggressive transgenic mouse model of brain amyloid with a significant (61%) reduction in
Aß plasma levels and a 30% reduction in Aß brain soluble and insoluble
fractions after only eight weeks of treatment.
*** Rogers SL, Doody RS, Mohs Rc. Arch Intern Med 1998; 158: 1021-31.
About Neurochem
Neurochem is focused on the development and commercialization of innovative therapeutics
for neurological disorders. The Company's staged pipeline of proprietary,
disease-modifying, oral products addresses critical unmet medical needs. Fibrillex™,
designated an orphan drug, is in a pivotal Phase II/III clinical trial for AA amyloidosis.
Alzhemed™ has completed a Phase II clinical trial. Cerebril™ is in a Phase II
trial for the prevention of hemorrhagic stroke caused by cerebral amyloid angiopathy.
Neurochem is also developing a product for the potential treatment of epileptic seizures
induced by traumatic brain injury. For additional information on Neurochem, please visit
our website at: (www.neurochem.com).
All of the statements contained in this news release, other than statements of fact which
are independently verifiable at the date hereof, are forward-looking statements. Such
statements, based as they are on the current expectations of management, inherently involve
numerous risks and uncertainties, known and unknown. Some examples of known risks are: the
impact of general economic conditions, general conditions in the pharmaceutical industry, changes
in the regulatory environment in the jurisdictions in which Neurochem does business, stock
market volatility, fluctuations in costs, and changes to the competitive environment due to
consolidation or otherwise. Consequently, actual future results may differ materially from
the anticipated results expressed in the forward-looking statements.
For further Information, please contact:
Dr. Lise Hébert
Vice President, Corporate Communications
lhebert@neurochem.com
275 Armand-Frappier
Laval (Quebec)
H7V 4A7
Tel: (450) 680-4500
Fax: (450) 680-4501
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