|
XIAFLEX™ CORD I Study Published in New
England Journal of Medicine
XIAFLEX Effective in Nonsurgically Treating MP and PIP
Joints With Dupuytren's Contractures, Regardless of Severity
MALVERN, PA, Sep 02, 2009 (MARKETWIRE via COMTEX) -- Auxilium
Pharmaceuticals, Inc. (NASDAQ: AUXL), a specialty
biopharmaceutical company, today announced that The New England
Journal of Medicine (NEJM) has published in its September 3rd
edition, the Company's pivotal CORD I Phase III clinical trial
of XIAFLEX™ (collagenase clostridium histolyticum) a novel,
first-in-class, biologic for the nonsurgical treatment of
Dupuytren's contracture. The CORD I study is the largest
prospective clinical trial ever conducted in the field of
Dupuytren's contracture. Treatment with XIAFLEX significantly
reduced the angle of contracture for patients with Dupuytren's
contracture in both their metacarpophalangeal (MP) and proximal
interphalangeal (PIP) joints, with clinically meaningful
responses in both less severe and more severe contractures.
"The results for MP and PIP joints that were treated with
XIAFLEX are compelling and compare favorably to surgery from
both an efficacy and safety point of view," said Larry Hurst,
M.D., study investigator and Professor and Chair, Department of
Orthopaedics at SUNY Stony Brook. "As noted in the publication,
the investigators believe that most patients with Dupuytren's
contracture would be candidates for treatment with XIAFLEX and
early intervention may be a prudent treatment approach. I
believe that XIAFLEX, as a new non-surgical treatment, could
potentially become the standard of care for Dupuytren's
contracture."
Auxilium has previously announced top line results of the CORD I
study, which indicate that 64.0% of all joints treated with
XIAFLEX achieved the primary endpoint of 0 degrees to 5 degrees
of full extension (normal or near normal straightening of the
treated finger) at 30 days after the last injection compared to
6.8% of patients treated with placebo (P < 0.001). Today's
publication includes stratified results of the study on a joint
by joint basis and by severity of the diseased joint.
Significant findings include:
-- 76.7% of MP joints were corrected to 0 degrees to 5 degrees
of full extension 30 days after the last injection of XIAFLEX
vs. 7.2% of MP joints treated with placebo (P < 0.001).
-- 88.9% of XIAFLEX-treated MP joints with baseline contracture
less than or equal to 50 degrees met the primary endpoint of
correction to 0 degrees to 5 degrees of full extension compared
with 57.7% of MP joints with baseline contracture > 50 degrees.
-- Mean change in contracture from baseline to 30 days after
last injection was 87.1% (from 48.0 degrees to 7.2 degrees) for
XIAFLEX-treated MP joints and 7.2% (from 45.4 degrees to 43.1
degrees) for placebo-treated MP joints (P < 0.001).
-- 40.0% of PIP joints were corrected to 0 degrees to 5 degrees
of full extension 30 days after the last injection of XIAFLEX
vs. 5.9% of PIP joints treated with placebo (P < 0.001).
-- 80.9% of the XIAFLEX-treated PIP joints with baseline
contracture less than or equal to 40 degrees met the primary
endpoint of correction to 0 degrees to 5 degrees of full
extension compared with 22.4% of PIP joints with baseline
contracture > 40 degrees.
-- Mean change in contracture from baseline to 30 days after
last injection was 64.5% for XIAFLEX-treated PIP joints and
11.4% for placebo-treated PIP joints (P < 0.001).
-- Mean change in arc of motion, a measurement of improvement in
range of motion, was improved significantly for all joints,
regardless of severity, treated with XIAFLEX compared to joints
treated with placebo (P < 0.001).
-- All twenty-six secondary endpoints were successfully met in
comparison to placebo (P less than or equal to 0.002).
"Dupuytren's cords may become disabling at an early stage of
contracture and can significantly impact many aspects of
patients' daily lives," said Dr. Tony DelConte, Chief Medical
Officer for Auxilium. "We believe these new data will be
well-received by the physician and patient community who have
expressed a need for an alternative treatment option to the
current standards of observation and, eventually, surgery."
The CORD I study was designed to assess the safety and efficacy
of XIAFLEX therapy in Dupuytren's contracture with MP or PIP
joint contractures greater than or equal to 20 degrees at
baseline. In the 3-month double-blind portion of the study, 308
patients with Dupuytren's contractures (stratified 2:1, MP joint
to PIP joint) were initially randomized to receive up to 3
once-monthly doses of XIAFLEX (0.58 mg) or placebo. There were
203 patients randomized to receive XIAFLEX and 103 patients
randomized to receive placebo that had primary joints able to be
evaluated.
The most commonly reported adverse events were edema peripheral,
contusion, injection-site hemorrhage, injection-site pain,
upper-extremity pain, tenderness, ecchymosis, injection-site
swelling, pruritus, skin laceration, lymph-node enlargement and
tenderness on palpation. Most treatment-related adverse events
were mild or moderate in intensity and the median resolution
time for all adverse events was 10 days, with limited or no
medical intervention. Three treatment-related serious adverse
events were reported: two tendon ruptures and one complex
regional pain syndrome. No deaths, clinically meaningful
hypersensitivity events, nerve injuries, arterial injuries or
significant changes in flexion or grip strength were observed.
Auxilium has filed a Biologics License Application (BLA) with
the U.S. Food and Drug Administration (FDA) for the use of
XIAFLEX in the treatment of advanced Dupuytren's disease. The
FDA's Division of Arthritis, Anesthesia and Rheumatoid Products
has scheduled an Advisory Panel to review XIAFLEX on September
16, 2009 at the Holiday Inn in Gaithersberg, MD. If approved by
the FDA, XIAFLEX is expected to be the first nonsurgical therapy
indicated for Dupuytren's contracture.
(table to follow)
CORD I Efficacy Endpoints (30 days after Last Injection)
XIAFLEX arm Placebo arm P-value
-------------- -------------- ----------
All Primary Joints
------------------
Percentage of joints achieving
a reduction in contracture to 64.0% 6.8% < 0.001
0 degrees-5 degrees, % (n) (130/203) (7/103)
Mean percent change in
contracture from baseline, -79.3% -8.6% < 0.001
% (degrees) (50.2 degrees/12.2 degrees) (49.1/45.7 degrees)
Percentage of contractures
achieving greater than or equal
to 50% reduction from 84.7% 11.7% < 0.001
baseline, % (n) (172/203) (12/103)
Mean change in arc of motion
from baseline, degrees 36.7 degrees 4.0 degrees < 0.001
Primary MP Joints
-----------------
Percentage of joints achieving
a reduction in contracture to 76.7% 7.2% < 0.001
0 degrees-5 degrees, % (n) (102/133) (5/69)
Percentage of joints with baseline
contractures less than or equal
to 50 degrees achieving 0 degrees-5 degrees, % (n) 88.9% - N/A*
Percentage of joints with baseline
contractures > 50 degrees achieving 0 degrees-5 degrees,
% (n) 57.7% - N/A*
Mean percent change in contracture -87.1% -7.2% < 0.001
from baseline, % (degrees) (48.0 degrees/7.2 degrees) (45.4
degrees/43.1 degrees)
Percentage of contractures achieving
greater than or equal to 50% 94.0% 11.6% < 0.001
reduction from baseline, % (n) (125/133) (8/69)
Mean change in arc of motion from
baseline, degrees 40.6 degrees 3.7 degrees < 0.001
Primary PIP Joints
------------------
Percentage of joints achieving a
reduction in contracture to 0 degrees-5 degrees, 40.0% 5.9% <
0.001
% (n) (28/70) (2/34)
Percentage of joints with baseline
contractures less than or equal
to 40 degrees achieving 0 degrees-5 degrees, % (n) 80.9% - N/A*
Percentage of joints with baseline
contractures > 40 degrees achieving 0 degrees-5 degrees,
% (n) 22.4% - N/A*
Mean percent change in contracture
from baseline, % (degrees) -64.5% -11.4% < 0.001
Percentage of contractures achieving
greater than or equal to 50% 67.1% 11.8% < 0.001
reduction from baseline, % (n) (47/70) (4/34)
Mean change in arc of motion from
baseline, degrees 29.0 degrees 4.7 degrees < 0.001
*Statistical significance was not pre-specified for these
endpoints
About Dupuytren's Contracture
Dupuytren's contracture is a condition that affects the
connective tissue that lies beneath the skin in the palm. The
disease is progressive in nature. Typically, nodules develop in
the palm as collagen deposits accumulate. As the disease
progresses, the collagen deposits form a cord that stretches
from the palm of the hand to the base of the finger. Once this
cord develops, the patient's fingers contract and the function
of the hand is impaired. Currently, surgery is the only
effective treatment. The incidence of Dupuytren's contracture is
highest in Caucasians, historically those of Northern European
descent, with a global prevalence of three to six percent of the
Caucasian population.(1) Most cases of Dupuytren's contracture
occur in patients older than 50 years.(2)
The most frequently affected parts of the hand associated with
Dupuytren's contracture are the joints called the Metacarpal
Phalangeal Joint, or MP joint, which is the joint closest to the
palm of the hand and the Proximal Intra-Phalangeal Joint, or the
PIP joint, which is the middle joint in the finger. The little
finger and ring finger are most frequently involved. There are
currently no drugs approved by the U.S. Food and Drug
Administration for Dupuytren's contracture, which is treated
primarily by an open surgical procedure.
(1) American Academy of Orthopaedic Surgeons.
http://orthoinfo.aaos.org/topic.cfm?topic=A00008
(2) Badalamente, M. A., Hurst, L. C. et al., Collagen as a
Clinical Target: Nonoperative Treatment of Dupuytren's Disease,
The Journal of Hand Surgery, (2002;27A:788-798)
About CORD I
The U.S. pivotal trial is a double-blind, randomized,
placebo-controlled study of XIAFLEX with 308 patients enrolled
in 16 sites throughout the U.S. The primary endpoint of the
study is to determine if XIAFLEX can reduce the contracture
angle in metacarpophalangeal (MP) or proximal interphalangeal
(PIP) joints to less than or equal to 5 degrees of normal. In
CORD I, MP and PIP patients were stratified in a 2:1 ratio.
All patients receiving XIAFLEX in the double-blind portion of
the study will be monitored for a minimum of 12 months following
initial dosing. After finishing the double-blind portion,
XIAFLEX and placebo patients are also eligible to receive
additional XIAFLEX injections for either unsuccessfully treated
joints or additional untreated joints during an open-label,
extended treatment period. This open-label phase was designed to
provide further data for the long-term safety and efficacy of
XIAFLEX injections in the treatment of Dupuytren's contracture.
About Auxilium
Auxilium Pharmaceuticals, Inc. is a specialty biopharmaceutical
company with a focus on developing and marketing to urologists,
endocrinologists, orthopedists and select primary care
physicians. Auxilium markets Testim(R) 1%, a topical
testosterone gel, for the treatment of hypogonadism through its
approximately 190-person sales and marketing team. Auxilium has
five projects in clinical development. XIAFLEX™ (collagenase
clostridium histolyticum), formerly referred to as AA4500, has
completed phase III clinical trials for the treatment of
Dupuytren's contracture, and the biologics license application
is under review at the FDA for the treatment of Dupuytren's
contracture. XIAFLEX is in phase IIb of development for the
treatment of Peyronie's disease and is in phase II of
development for treatment of Frozen Shoulder syndrome (Adhesive
Capsulitis). Auxilium's transmucosal film product candidate for
the treatment of overactive bladder (AA4010) and its fentanyl
pain product using its transmucosal delivery system are in phase
I of development. The Company is currently seeking a partner to
further develop these transmucosal film product candidates.
Auxilium has rights to additional pain products and products for
hormone replacement and urologic disease using its transmucosal
film delivery system. Auxilium also has options to all
indications using XIAFLEX for non-topical formulations. For
additional information, visit
http://www.auxilium.com.
SAFE HARBOR STATEMENT UNDER THE PRIVATE SECURITIES
LITIGATION REFORM ACT OF 1995
This release contains "forward-looking-statements" within the
meaning of The Private Securities Litigation Reform Act of 1995,
including statements regarding patients who may be candidates
for treatment with XIAFLEX and at what stage of disease
progression; the interpretation of clinical data; the timing of
the FDA Advisory Committee to review XIAFLEX; the timing of FDA
review of the BLA for XIAFLEX and the approval thereof; the
number of patients with Dupuytren's contracture; products in
development for Peyronie's disease, Frozen Shoulder syndrome,
overactive bladder, pain, hormone replacement and urologic
disease; and all other statements containing projections,
statements of future performance or expectations, or statements
of plans or objectives for future operations (including
statements of assumption underlying or relating to any of the
foregoing). You can identify these statements by the fact that
they use words such as "believe," "appears," "may," "could,"
"will," "estimate," "continue," "anticipate," "intend,"
"should," "plan," "expect," and other words and terms of similar
meaning in connection with any discussion of projections, future
performance or expectations, plans or objectives for future
operations (including statements of assumption underlying or
relating to any of the foregoing). Actual results may differ
materially from those reflected in these forward-looking
statements due to various factors, including further evaluation
of clinical data, results of clinical trials, decisions by
regulatory authorities as to whether and when to approve drug
applications, and general financial, economic, regulatory and
political conditions affecting the biotechnology and
pharmaceutical industries and those discussed in Auxilium's
Annual Report on Form 10-K for the year ended December 31, 2008
and in Auxilium's Quarterly Report on Form 10-Q for the period
ended June 30, 2009 under the heading "Risk Factors," which are
on file with the Securities and Exchange Commission (the "SEC")
and may be accessed electronically by means of the SEC's home
page on the Internet at
http://www.sec.gov
or by means of Auxilium's home page on the Internet at
http://www.Auxilium.com under the heading "For Investors --
SEC Filings." There may be additional risks that Auxilium does
not presently know or that Auxilium currently believes are
immaterial which could also cause actual results to differ from
those contained in the forward-looking statements. Given these
risks and uncertainties, any or all of these forward-looking
statements may prove to be incorrect. Therefore, you should not
rely on any such factors or forward-looking statements.
In addition, forward-looking statements provide Auxilium's
expectations, plans or forecasts of future events and views as
of the date of this release. Auxilium anticipates that
subsequent events and developments will cause Auxilium's
assessments to change. However, while Auxilium may elect to
update these forward-looking statements at some point in the
future, Auxilium specifically disclaims any obligation to do so.
These forward-looking statements should not be relied upon as
representing Auxilium's assessments as of any date subsequent to
the date of this release.
Contact
James E. Fickenscher
Chief Financial Officer
Auxilium Pharmaceuticals, Inc.
+1-484-321-5900
or
William Q. Sargent Jr.
Vice-President, Investor Relations and Corporate Communications
+1-484-321-5900
Source
Auxilium Pharmaceuticals, Inc.
|
