Successful Proof-of-Concept Study with Reductions in Psoriatic
Infiltrate Thickness, Erythema and Clinical Skin Assessments
Conference Call Today at 8:30 a.m. ET
CAMBRIDGE, Mass.--(BUSINESS WIRE)--March 12, 2008--CombinatoRx,
Incorporated (NASDAQ: CRXX) today announced top line results of its
randomized, blinded, placebo-controlled Phase 2 proof-of-concept
clinical trial of CRx-191 in plaque psoriasis. CRx-191 is a topical
synergistic combination drug candidate in development for psoriasis
and other steroid-responsive dermatoses. The trial evaluated the
efficacy, safety and tolerability of two doses of CRx-191 compared to
placebo in subjects with psoriasis. In this trial, the high dose of
CRx-191 demonstrated an 81% reduction in psoriatic infiltrate from
baseline to day 12, compared to 11% for placebo. This reduction
demonstrated with CRx-191 was statistically significant (P<0.0001).
Similarly, CRx-191 demonstrated a 58% reduction in erythema (redness)
from baseline to day 12, as compared to 6% with placebo. This effect
was also statistically significant (P<0.0001). In clinical assessments
of skin condition, CRx-191 demonstrated clinically significant
improvements from baseline to day 12 in 100% of all test fields, as
compared to 0% for placebo. The high and low doses of CRx-191
performed similarly, although CRx-191 high dose was numerically
superior to low dose on most measures.
CRx-191 was also compared to its individual components on multiple
measures such as psoriatic infiltrate thickness, erythema and clinical
skin condition and produced greater improvements than mometasone and
nortriptyline alone. Although this trial was not powered to achieve
statistical significance in comparison to its components, CRx-191 was
superior in all aspects and achieved statistical significance for
erythema. The mean reduction in erythema for CRx-191 compared to
mometasone was statistically significant (P=0.017) and numerically
greater on infiltrate thickness reduction and clinical skin assessment
scores. CRx-191 induced statistically significant reductions compared
with nortriptyline on infiltrate thickness (P<0.0001) and erythema
(P<0.0001), and improved clinical skin assessment scores compared with
nortriptyline.
"I am encouraged by the statistically significant improvements
demonstrated with CRx-191 over vehicle in psoriatic infiltrate
thickness as well as with CRx-191 in comparison to its individual
components on other measures, including erythema and clinical
assessment scores. CRx-191 warrants further investigation to determine
its appropriate role within the psoriasis treatment paradigm,"
commented Johannes Gassmueller, M.D., principal investigator for the
study, bioskin GmbH, Berlin, Germany.
CRx-191 was well tolerated and there were no adverse events
reported for any subjects treated in this trial. An earlier safety
study conducted in healthy volunteers evaluated the tolerability of
CRx-191 and its potential to induce skin thinning, a key treatment
limiting side effect of many potent glucocorticoids. In this study,
the CRx-191 combination did not induce skin thinning above mometasone
alone.
"It is encouraging to see that the synergy demonstrated in early
screening and preclinical models has successfully translated into
human clinical data," commented Alexis Borisy, President and CEO of
CombinatoRx. "These data suggest there may be two potential product
opportunities to further explore for CRx-191: a high-potency topical
targeting psoriatic flares and a version containing a lower-dose of
mometasone to be used as maintenance therapy between flares."
The development path for CRx-191 will be determined in
consultation with advisors in the coming months. Simultaneously,
discussions with prospective partners are being initiated to secure
resources focused on maximizing the potential of CRx-191, which is the
first in a series of topical dermatology product candidates within the
CombinatoRx portfolio. Clinical trials to evaluate CRx-197, another
topical dermatology candidate, are also planned during 2008.
About CRx-191
CRx-191 is a topical synergistic combination drug candidate with a
novel multi-target mechanism that inhibits tumor necrosis factor-alpha
and interferon-gamma, key cell mediators of dermal inflammation.
CRx-191 contains a mid-potency glucocorticoid, mometasone, and a very
low dose of the tricyclic anti-depressant, nortriptyline. CRx-191 is
thought to work through a novel mechanism of action in which
nortriptyline amplifies mometasone's anti-inflammatory activities
without enhancing glucocorticoid side effects to provide a potent
topical glucocorticoid with an improved therapeutic index. We have
developed a novel topical cream formulation of CRx-191 which provides
the first topical formulation of nortriptyline. We have demonstrated
that the CRx-191 class of tricyclics and glucocorticoids are safe and
effective in multiple experimental and preclinical models of
inflammation. CRx-191 is under development for psoriasis and other
glucocorticoid-responsive dermatoses. In addition to this Phase 2a
clinical trial for plaque psoriasis, an earlier safety study conducted
in healthy volunteers evaluated the tolerability of CRx-191 and its
potential to induce skin thinning, a key treatment limiting side
effect of many potent glucocorticoids. In this study, the CRx-191
combination did not induce skin thinning above mometasone alone.
About the Trial Design
This Phase 2a clinical trial was a 12-day, single-center,
randomized, double-blind, placebo-controlled study evaluating the
efficacy, safety and tolerability of CRx-191 in reducing psoriatic
infiltrate band thickness (extent of psoriatic inflammation) in
subjects with plaque psoriasis. Twenty-one subjects were enrolled with
chronic, stable plaque psoriasis with a single plaque covering an area
sufficient for six treatment fields. All subjects received all
treatments under an occlusive dressing in the selected treatment area:
CRx-191 low dose (0.1% mometasone furoate + 0.05% nortriptyline),
CRx-191 high dose ((0.1% mometasone furoate + 0.1% nortiptyline), 0.1%
mometasone alone, 0.05% nortriptyline alone, 0.1% nortriptyline alone
and placebo. Endpoints included reduction from baseline in psoriatic
infiltrate thickness as measured by high frequency ultrasound,
erythema as measured by chromametry, clinical skin condition score and
histologic analysis of inflammatory biomarkers. Statistical analysis
for all endpoints was conducted by calculating the mean of the
difference in change from baseline to day 12 between CRx-191 and each
of its comparator arms. Data provided are per protocol.
Infiltrate band thickness as measured by ultrasound is a well
recognized method for clinical assessment of anti-psoriatic action.
The clinical relevance of the test has been documented (Wendt 1982,
Gassmueller 1993). By using an occlusive dressing, six test fields can
be examined per subject, allowing intra-individual test site
comparison, with the goal of providing clinically meaningful results
using a relatively small cohort of subjects.
About Psoriasis
Psoriasis is a chronic inflammatory skin disease affecting between
6 and 7.5 million people in the United States characterized by skin
thickening, redness and scaling. Dermatologists favor the use of local
topical delivery in all but the most severe cases of psoriasis to
limit systemic exposure and avoid systemic side effects.
Glucocorticoids are the most commonly prescribed class of topical
treatment used in psoriasis. Existing topical glucocorticoids are
available in a wide range of potencies. Currently available
high-potency topical glucocorticoids are associated with local skin
toxicities, including thinning following only short periods of
exposure and irreversible skin atrophy after longer treatment periods.
A topical selective glucocorticoid amplifier that enhances potency
without enhancing side effects would provide a significantly improved
treatment option for psoriasis patients.
Conference Call Information
CombinatoRx will host a conference call to discuss these results
at 8:30 a.m. ET on Wednesday, March 12, 2008. To access the call,
please dial 800-259-0251 (domestic) or 617-614-3671 (international)
five minutes prior to the start time and provide the passcode
62236398. A replay of the call will be available from 7:00 p.m. ET on
March 12, 2008 until March 19, 2008. To access the replay, please dial
888-286-8010 (domestic) or 617-801-6888 (international), and provide
the passcode 44463232. A live audio webcast of the call will also be
available on the "Investors" section of the Company's website,
www.combinatorx.com. An archived webcast will be available on the
CombinatoRx website approximately two hours after the event and will
be archived for 14 days.
About CombinatoRx
CombinatoRx, Incorporated (CRXX) is pioneering the new field of
synergistic combination pharmaceuticals and has a broad product
portfolio in Phase 2 clinical development. Going beyond traditional
combinations, CombinatoRx creates product candidates with novel
mechanisms of action striking at the biological complexities of human
disease. The lead programs in the CombinatoRx portfolio are advancing
into later stage clinical trials based on the strength of multiple
positive Phase 2a results. This portfolio is internally generated from
the CombinatoRx proprietary drug discovery technology which provides a
renewable and previously untapped source of novel drug candidates. The
Company was founded in 2000 and is located in Cambridge,
Massachusetts. To learn more about CombinatoRx, please visit
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 CombinatoRx, its product candidate CRx-191, its clinical,
commercial and therapeutic potential, its plans for clinical
development of CRx-191 and CRx-197, its business development plans and
its drug discovery technology. These forward-looking statements about
future expectations, plans and prospects of CombinatoRx and CRx-191
and CRx-197 involve significant risks, uncertainties and assumptions,
including risks related to the Company's ability to enroll and
successfully complete its clinical trials of CRx-191 and CRx-197, the
Company's ability to develop a proprietary formulation of CRx-191 and
CRx-197, potential difficulty and delays in obtaining regulatory
approval for the sale and marketing of CRx-191 and CRx-197, the
unproven nature of the CombinatoRx drug discovery technology, the
Company's ability to enter into collaborative relationships or obtain
additional financing or funding for its research and development and
those other risks that can be found in the "Risk Factors" section of
the CombinatoRx Annual Report on 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 contemplated by
these forward-looking statements. 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) 2008 CombinatoRx, Incorporated. All rights reserved.
CONTACT: CombinatoRx, Incorporated
Robert Forrester, 617-301-7100
Executive Vice President, Chief Financial Officer
Fax: 617-301-7010
rforrester@combinatorx.com
or
Gina Nugent, 617-301-7099
VP, Corporate Communications and IR
Fax: 617-301-7010
gnugent@combinatorx.com
SOURCE: CombinatoRx, Incorporated
