XIAFLEX Effective in Nonsurgically Treating MP and PIP Joints With Dupuytren's Contractures, Regardless of SeverityMALVERN, 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(TM) (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(TM) (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
Email Contact
or
William Q. Sargent Jr.
Vice-President, Investor Relations and Corporate Communications
+1-484-321-5900
Email Contact
SOURCE: Auxilium Pharmaceuticals, Inc.