CALGARY, Alberta, July 23, 2014 /PRNewswire/ --
In addition, preliminary results from an Australian sponsored
trial have yet to verify whether the mechanism of RVX-208 action
may affect glucose metabolism.
Resverlogix Corp. (TSX: RVX) announced today findings from the
recent analysis of Major Adverse Cardiovascular Events (MACE) data
in patients with diabetes mellitus (DM) enrolled in both the ASSURE
and SUSTAIN trials. In ASSURE, MACE was a pre-specified endpoint
and it was confirmed to be statistically and significantly reduced
in patients with DM treated with RVX-208 vs. placebo. The latest
finding reinforces the potential benefit of RVX-208, a first in
class BET-inhibitor, to impact MACE and additional metabolic
parameters over a duration of 6 months in high risk vascular
patients with DM and low HDL.
ASSURE enrolled a population who had high cardiovascular risk
with low HDL-C and amongst these almost 100 patients had DM.
Approximately 75% (precise numbers here and below are reserved for
future publications and abstracts) of these patients with DM were
given RVX-208 while the remainder received placebo. Unexpectedly,
we noted a statistically significant relative risk reduction in
MACE of more than 65% in patients with DM treated with RVX-208 vs.
placebo. While this marked and significant reduction of MACE in the
ASSURE data alone is already very important, it is further
supported by the analysis of data from SUSTAIN, a trial with a
population almost identical to that in ASSURE. When data from both
ASSURE and SUSTAIN were pooled, patients with a history of DM
totaled almost 200. Roughly 2/3 of these patients received RVX-208
while the remainder were given placebo. Analysis of the pooled
patient data showed again that RVX-208 treatment led to a
statistically significant relative risk reduction in MACE of
>65% vs. placebo. In patients with DM, RVX-208's ability to
reduce MACE is very important because the majority of the patients
die from cardiovascular diseases.
In the ongoing analysis of pooled ASSURE and SUSTAIN data, many
biomarkers of cardiovascular risk were examined but the above
findings made blood glucose levels of specific interest. Results of
analysis showed that patients with DM given RVX-208 tended to have
lower blood glucose vs. placebo. But specifically in patients with
DM who had low HDL, the blood glucose was significantly lower
following treatment with RVX-208 vs. placebo. Furthermore, the time
required for RVX-208 to reduce blood glucose was not observed until
at least 12 weeks following initiation of treatment.
While the analyses of ASSURE data was being conducted, a new
trial looking at metabolic parameters was in progress conducted at
the Baker IDI Heart and Diabetes Institute (Melbourne, Australia). The investigators
postulated that the RVX-208 induced rise in ApoA-I/HDL-C may impact
pancreatic insulin secretion and thereby lower blood glucose
(detected using an oral glucose tolerance test). Patients (n=23)
with pre-diabetes mellitus (also called metabolic syndrome) were
enrolled in the study and given 200 mg/day RVX-208 for a short
duration of only 4 weeks. The preliminary results were not
consistent with their hypothesis. However, this finding was useful
in understanding the ASSURE data because for RVX-208 to reduce
blood glucose in patients with DM required at least 12 weeks of
treatment. Analysis of data from the new trial beyond preliminary
results reported here will include; HDL abundance, lipidomics,
platelet aggregation, monocyte activation and neutrophil adhesion.
Resverlogix is planning to submit the above important findings and
other new data to scientific journals for peer review prior to
publication and presentation at leading medical conferences.
"Resverlogix will continue to examine in detail the data from
its numerous human clinical trials specifically for important
biomarkers that may play a role in high risk vascular diseases such
as acute coronary syndrome, type 2 diabetes mellitus and chronic
kidney disease" stated Donald
McCaffrey, President and Chief Executive Officer of
Resverlogix. "These are new and important findings that RVX-208,
when added to standard of care medicine, reduces MACE in patients
with DM" added McCaffrey.
"The new observations above and continued analysis of our
extensive database are very important for establishing the emerging
role of BET inhibition in high risk vascular disease and especially
in those with DM" stated Dr. Jan
Johansson, Senior Vice President of Medical Affairs at
Resverlogix. "The new information that we have gained was essential
in designing the next RVX-208 clinical trial to facilitate product
registration" Dr. Johansson further commented.
About Diabetes Mellitus & Glucose
Diabetes mellitus is a group of metabolic diseases in which a
patient's blood glucose is high. Untreated DM is a leading risk
factor for heart disease, kidney failure, loss of nerve function,
amputations and damage to the eyes. A primary defect in DM is the
inability of the pancreas to provide enough insulin for the body or
ineffective actions of insulin, thus leading to increased blood
glucose.
About RVX-208
RVX-208 is a first-in-class small molecule that selectively
inhibits BET bromodomains. RVX-208 functions via several mechanisms
such as removing atherosclerotic plaque via reverse cholesterol
transport (RCT), the natural process through which atherosclerotic
plaque is transported out of the arteries and removed from the body
by the liver. RVX-208 increases production of Apolipoprotein A-I
(ApoA-I), the key building block of functional high-density
lipoprotein (HDL) particles and the type required for RCT. These
newly produced, functional HDL particles are flat and empty and can
efficiently remove plaque and stabilize or reverse atherosclerotic
disease. Analysis of recent clinical trials data showed that
RVX-208 significantly reduces coronary atherosclerosis and major
adverse cardiac events in patients with CVD who have a low level of
HDL and elevated CRP, a population with unmet medical need. ApoA-I
enhancement and glucose lowering have been reported to exert
beneficial effects in Alzheimer's disease and Diabetes Mellitus.
RVX-208 also has anti-inflammatory effects including effects on
Interleukin-6 inhibition, vascular cell adhesion-1 and monocyte
chemotactic protein-1, factors known to be involved in
atherosclerosis and plaque stability.
About Resverlogix
Resverlogix Corp. (TSX: RVX) is a clinical stage cardiovascular
company developing compounds involving a therapeutic increase in
ApoA-I. Resverlogix's RVX-208 is a first-in-class small molecule
for the treatment of atherosclerosis and other chronic diseases
such as Diabetes Mellitus and Alzheimer's disease. RVX-208 is the
first BET bromodomain inhibitor in clinical trials. Resverlogix's
common shares trade on the Toronto Stock Exchange (TSX: RVX). For
further information please visit http://www.resverlogix.com. We can
be followed on our blog at http://www.resverlogix.com/blog.
This news release may contain certain forward-looking
information as defined under applicable Canadian securities
legislation, that are not based on historical fact, including
without limitation statements containing the words "believes",
"anticipates", "plans", "intends", "will", "should", "expects",
"continue", "estimate", "forecasts" and other similar expressions.
In particular, this news release includes forward looking
information relating to research and development activities and the
potential role of RVX-208 in the treatment of atherosclerosis and
other chronic diseases. Our actual results, events or developments
could be materially different from those expressed or implied by
these forward-looking statements. We can give no assurance that any
of the events or expectations will occur or be realized. By their
nature, forward-looking statements are subject to numerous
assumptions and risk factors including but not limited to those
associated with the success of research and development programs,
clinical trial programs including possible delays in patient
recruitment, the regulatory approval process, competition, securing
and maintaining corporate alliances, market acceptance of the
Company's products, the availability of government and insurance
reimbursements for the Company's products, the strength of
intellectual property, financing capability, the potential dilutive
effects of any financing, reliance on subcontractors and key
personnel and additional assumptions and risk factors discussed in
our Annual Information Form and most recent MD&A which are
incorporated herein by reference and are available through SEDAR
at http://www.sedar.com. The forward-looking
statements contained in this news release are expressly qualified
by this cautionary statement and are made as of the date hereof.
The Company disclaims any intention and has no obligation or
responsibility, except as required by law, to update or revise any
forward-looking statements, whether as a result of new information,
future events or otherwise.
For further information:
Company Contacts:
Donald J. McCaffrey
President and CEO
Resverlogix Corp.
Phone: +1-403-254-9252
Email: don@resverlogix.com
Kenneth Lebioda
SVP Business & Corporate Development
Resverlogix Corp.
Phone: +1-403-254-9252
Email: ken@resverlogix.com