CombinatoRx Reports Positive Results for CRx-170 in Phase 2 Proof-of-Concept Asthma Clinical Trial; Novel Combination Drug Candidate Demonstrates Clinical Benefit on Forced Expiratory Volume (FEV1)
CAMBRIDGE, Mass.--(BUSINESS WIRE)--April 18, 2006--CombinatoRx,
Incorporated (NASDAQ: CRXX) today announced positive results of its
single blind, phase 2, proof-of-concept clinical trial of CRx-170 in
patients with asthma. CRx-170 is a novel synergistic combination drug
candidate containing low dose budesonide and low dose nortriptyline.
In this trial CRx-170 provided clinical benefit on FEV1 and
demonstrated activity on immuno-modulatory markers. As measured by
FEV1, the standard clinical measure of breathing capacity in asthma
and chronic obstructive pulmonary disease (COPD), the novel
combination CRx-170 demonstrated a statistically significant
improvement from treatment baseline. CRx-170 was generally well
tolerated and there were no serious adverse events reported.
In the study, one week of dosing CRx-170 demonstrated a
statistically significant mean percentage improvement (increase) in
FEV1 from the treatment baseline of the study of approximately 6%
(p=0.045). Neither low dose nortriptyline as a single agent nor low
dose budesonide as a single agent showed significant improvement in
FEV1 from the separate study baseline used to evaluate the single
agents (approximately 2% decrease for low dose nortriptyline, p=0.466;
approximately 5% decrease for low dose budesonide, p=0.251). In the
wheal and flare skin test, otherwise known as the Late Allergen
Response (LAR), CRx-170 decreased the area of LAR by more than 50%
(p=0.053). CRx-170 did not show a modulation of the inflammatory
marker CD163 from the treatment baseline, although nortriptyline
clearly did decrease CD163 on its own. Analysis of additional
measurements and the final analysis of these data is ongoing. The most
common adverse events related to CRx-170 were dry mouth, drowziness,
constipation and headache; known effects of nortriptyline.
"The observed effect of CRx-170 in such a short period of dosing,
as measured by FEV1, the most clinically relevant endpoint and
generally accepted measure of clinical activity, suggests that CRx-170
may have potential as a novel agent for the treatment of pulmonary
diseases such as asthma and COPD," said Dr. Jan Lessem, Chief Medical
Officer of CombinatoRx. "Given these signals of clinical activity and
observed immunological activity, CRx-170 certainly merits further
clinical studies."
"This proof of concept trial provides another successful
translation of our discovery technology into positive clinical
results" commented Alexis Borisy, President and CEO of CombinatoRx.
"We are pleased to see the activity of CRx-170 where the low doses of
these individual agents have not shown clinical activity, and we look
forward to the continuing development of the CombinatoRx pipeline."
About the Trial Design
This clinical trial was conducted over an approximately 17-week
per patient period and was a single center, single blind, dose
de-escalation study. The proof-of-concept phase 2 study was primarily
descriptive in design, with a change in circulating monocyte CD163, an
inflammatory marker, designated as its primary endpoint. Secondary
endpoints of the study included clinical measures such as spirometry
(i.e., FEV1), evening peak expiratory flow, and the use of rescue
medication and reduction in other inflammatory markers including wheal
and flare response.
Patients were sequentially treated with decreasing oral doses of
nortriptyline and budesonide as single agents, with washout periods
between each treatment, followed by 1-week treatment with
nortriptyline and 1-week with CRx-170. During the nortriptyline alone
and budesonide alone phases, changes in FEV1 were measured versus
study baseline, which was set on the first day of dose de-escalation
of nortriptyline as a single agent. During the CRx-170 treatment
phase, changes in FEV1 were measured from treatment baseline, which
was set following the last washout from the single agent dosing
period. During the treatment period with CRx-170, patients were given
3 mg of budesonide orally and the lowest dose of nortriptyline from
the de-escalation phase.
Patients with mild allergic asthma were enrolled in the trial. To
be eligible, patients had to have a history of bronchial asthma for at
least 6 months as defined by ATS criteria, a positive wheal and flare
skin test response to allergens, and FEV1 greater than or equal to 60%
of the predicted FEV1. Of the nineteen patients enrolled, seventeen
completed treatment.
About CRx-170
CRx-170 is a novel, orally available syncretic drug candidate in
Phase 2 clinical development. A syncretic drug comprises two compounds
that are designed to act synergistically through multiple pathways to
provide a novel therapeutic effect which neither component alone can
achieve. CRx-170 contains a low dose of the steroid budesonide and a
low dose of nortriptyline. The target product profile for CRx-170 is
to selectively amplify certain elements of budesonide's
anti-inflammatory and immunomodulatory activities, without replicating
its side effects. CRx-170 was discovered using the CombinatoRx
proprietary combination High Throughput Screening (cHTS(TM))
technology. We plan to develop CRx-170 in a unique formulation for the
treatment of pulmonary or additional immuno-inflammatory diseases.
CRx-170 is one of a portfolio of six product candidates that
CombinatoRx is currently testing in phase 2 clinical trials.
About Asthma
Asthma is a chronic inflammatory disorder of the airways
characterized by two primary components: inflammation and
bronchoconstriction. The full cause of asthma is undetermined,
although heredity, allergens, and environmental factors play a role in
its development. Currently, the strongest identifiable predisposing
factor for developing asthma is the genetic predisposition for the
development of an immune response to common aeroallergens.
Asthma is estimated to occur in over 150 million people worldwide
and the prevalence is increasing. The goal of asthma treatment is to
prevent and control asthma symptoms, reduce the frequency and severity
of asthma exacerbations, and reverse airflow obstruction. Several
classes of drugs are currently available to treat patients with asthma
and they are often classified as either long-term control medications
or quick-relief medications. Long-term control medications are taken
daily to maintain control of persistent asthma. The drugs in this
category include anti-inflammatory agents (e.g., glucocorticoids),
long acting bronchodilators, and leukotriene modifiers. Quick relief
medications are taken to control acute asthma symptoms. The drugs in
this category include short acting bronchodilators, anti-cholinergics,
and anti-inflammatory agents.
About CombinatoRx
CombinatoRx, Incorporated is a biopharmaceutical company focused
on developing new medicines built from synergistic combinations of
approved drugs, designed to attack disease on multiple fronts.
CombinatoRx applies its proprietary combination drug discovery
technology to identify new combination product candidates in a number
of disease areas, including immuno-inflammatory disease, oncology,
metabolic disease, neurodegenerative disease and infectious disease.
We are currently developing a portfolio of 6 product candidates
targeting multiple diseases which were discovered by applying our
proprietary screening technology. For further information, please
visit the CombinatoRx website at www.combinatorx.com.
Forward-Looking Statement
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995
concerning the Company's clinical trial results for CRx-170, including
its biological activity, its plans for further research and
development of its CRx-170 product candidate, its plans regarding the
formulation of CRx-170, its plans with respect to the research and
development of the other product candidates in its portfolio, and its
drug discovery technology. These forward-looking statements about
future expectations, plans and prospects of CombinatoRx involve
significant risks, uncertainties and assumptions, including risks
related the Company's ability to initiate and successfully complete
clinical trials of its product candidates, potential difficulty and
delays in obtaining regulatory approval for the sale and marketing of
its product candidates, the Company's ability to develop a new
formulation for CRx-170, the unproven nature of its drug discovery
technology, the Company's ability to obtain additional funding for its
research and development and those other risks that can be found in
the "Risk Factors" section of the CombinatoRx Annual Report Form 10-K
on file with the Securities and Exchange Commission and the other
reports that CombinatoRx periodically files with the Securities and
Exchange Commission. Actual results may differ materially from those
CombinatoRx projects.
In addition, the forward-looking statements included in this press
release represent CombinatoRx views as of the date of this release.
CombinatoRx does not undertake to update any of these forward-looking
statements to reflect a change in its views or events or circumstances
that occur after the date of this release.
(c) 2006 CombinatoRx, Incorporated. All rights reserved.
CONTACT: CombinatoRx, Incorporated
Robert Forrester, 617-301-7100
Fax: 617-301-7010
rforrester@combinatorx.com
or
Gina Nugent, 617-301-7099
Fax: 617-301-7010
gnugent@combinatorx.com
SOURCE: CombinatoRx, Incorporated