"RVX-208 lowers Inflammation and MACE Events while Regressing Atheroma
in High Risk CVD Patients"
TSX Exchange Symbol: RVX
CALGARY, Nov. 4, 2013 /PRNewswire/ - Resverlogix Corp. (TSX:RVX) today
announced two additional results from the ongoing analysis of its Phase
2b ASSURE clinical trial using intravascular ultrasound (IVUS) to study
high-risk cardiovascular disease (CVD) patients for assessing benefits
of RVX-208. This lead molecule is a member of a new class of compounds
that affects cellular epigenetics by specifically inhibiting a BET
protein leading to enhanced apoA-I gene transcription and the creation
of functional HDL particles for treating atherosclerotic CVD. Since
the completion of the ASSURE trial the continued analysis of the data
have yielded two new findings that detail the effects of RVX-208 on
vascular inflammation and virtual histology.
First, the data showed statistically significant improvements in
coronary IVUS atheroma measurements and Major Adverse Cardiac Events
(MACE) in patients with a high (>2.0 mg/dL) serum high sensitivity
C-Reactive Protein (hsCRP). Serum levels of this biomarker when >2.0
mg/dL reflect a heightened state of inflammation that is a well-known
and major component of CVD risk. Patients with hsCRP>2.0 mg/dL at time
of entry into ASSURE totaled n=184 of which n=54 were given placebo
while n=130 received RVX-208. In the RVX-208 treated patients, there
was a 60% reduction (p<0.0001) in hsCRP vs. baseline and (p=0.054) vs.
placebo. Furthermore atheroma regression was observed in patients
treated with RVX-208 as measured by percent atheroma volume (PAV),
total atheroma volume (TAV) regressed, and the worst 10mm TAV segment
by -0.75% (p<0.03), -6.3mm3 (p<0.001) and -2.63mm3 (p<0.001), respectively vs. baseline. Equally intriguing and perhaps
more important is that in RVX-208 treated patients with hsCRP>2.0 mg/dL
the incidence of MACE was lower by 63% (p=0.023) vs. placebo. The
preceding observation is of value in that hsCRP of >2.0 mg/dL is well
known to be clinically important in predicting CVD risk.
The second new observation arises from a pre-specified exploratory
endpoint in ASSURE gathered using a new catheter (Volcano Revolution
45mghz) designed for radiofrequency analysis of the IVUS signal. Data
from this catheter reveals so called virtual histology IVUS (VH-IVUS),
an emerging technology that is useful for assessing tissue
characteristics of an atherosclerotic plaque. VH-IVUS data was
analyzed to provide insight into vulnerability of an atherosclerotic
plaque to rupture and its relationship to future cardiovascular risk.
In ASSURE, while all (n=323) patients were studied using IVUS, 87 of
these were examined using the Volcano Revolution catheter to gather
VH-IVUS information. This information was used to reflect plaque
vulnerability by calculating the ratio of necrotic core to dense
calcium (NC/DC) as established by Missel et al. (Am J Cardiol 2008;
NC/DC ratio). The NC/DC ratio in RVX-208 treated patients (n=61) was
significantly lower by -7.5% (p<0.03) vs. baseline while those (n=24)
given placebo had a non-significant reduction of -3.8% (p=0.47) vs.
baseline. The initial VH-IVUS findings show that the actions of RVX-208
improved the NC/CS ratio pointing to less vulnerability of the
atherosclerotic plaque for rupture.
"The ongoing analysis of the ASSURE data continues to yield positive
findings that provide valuable information as to the large market
segment where RVX-208 will have the best impact in reducing CVD risk",
stated Donald McCaffrey, President and Chief Executive Officer of
Resverlogix. "The addition of today's findings to the previously
announced impact of RVX-208 to regress PAV (-1.43%, p=0.001) in ASSURE
patients with low HDL-C given rosuvastatin further define a large high
risk population where RVX-208 illustrates profound effects to reduce
atheroma volume and plaque vulnerability. Together these findings help
explain the observed reduction in MACE events. Continued analysis of
the ASSURE data will not only broaden our understanding but also
provide a clear pathway for our future clinical trials of RVX-208",
said Mr. McCaffrey.
"We are delighted to see that RVX-208 had a pronounced effect in
patients with established CVD, low HDL-C and a heightened state of
inflammation" remarked Dr. Jan Johansson, Senior Vice President of
Medical Affairs of Resverlogix. "This is very useful information that
will lead to a personalized medicine approach for patient selection in
our future trials of RVX-208. The pathogenesis of atherosclerosis is
known to involve a complex interplay between lipids and inflammation.
Lessons learned from the exploratory ASSURE trial show us how to
maximize the clinical benefits of RVX-208 in combating these factors as
development of RVX-208 progresses", Dr. Johansson added.
RVX-208 is a first-in-class small molecule that inhibits BET
bromodomains. RVX-208 functions by 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. ApoA-I may also exert beneficial effects in Alzheimer's
disease and Diabetes Mellitus.
Resverlogix Corp. (TSX:RVX) is a clinical stage biotechnology company
developing compounds involving ApoA-I production. RVX-208 is a
first-in-class small molecule in development for the treatment of
diseases such as atherosclerosis, 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 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
diseases such as atherosclerosis, Diabetes Mellitus and Alzheimer's
disease. 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 those discussed in our Annual Information Form and
most recent MD&A which are incorporated herein by reference and are
available through SEDAR at 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.
Donald J. McCaffrey
President and CEO
SVP Business & Corporate Development
SOURCE Resverlogix Corp.