-- 76.7% of MP joints were corrected to 0° to 5° 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° met the primary endpoint of correction to 0° to 5° of full
extension compared with 57.7% of MP joints with baseline contracture > 50°.
-- Mean change in contracture from baseline to 30 days after last
injection was 87.1% (from 48.0° to 7.2°) for XIAFLEX-treated MP joints and
7.2% (from 45.4° to 43.1°) for placebo-treated MP joints (P < 0.001).
-- 40.0% of PIP joints were corrected to 0° to 5° 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° met the primary endpoint of correction to 0° to 5° of
full extension compared with 22.4% of PIP joints with baseline contracture
> 40°.
-- 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° 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°-5°, % (n) (130/203) (7/103)
Mean percent change in
contracture from baseline, -79.3% -8.6% < 0.001
% (degrees) (50.2°/12.2°) (49.1/45.7°)
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° 4.0° < 0.001
Primary MP Joints
-----------------
Percentage of joints achieving
a reduction in contracture to 76.7% 7.2% < 0.001
0°-5°, % (n) (102/133) (5/69)
Percentage of joints with baseline
contractures less than or equal
to 50° achieving 0°-5°, % (n) 88.9% - N/A*
Percentage of joints with baseline
contractures > 50° achieving 0°-5°,
% (n) 57.7% - N/A*
Mean percent change in contracture -87.1% -7.2% < 0.001
from baseline, % (degrees) (48.0°/7.2°) (45.4°/43.1°)
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° 3.7° < 0.001
Primary PIP Joints
------------------
Percentage of joints achieving a
reduction in contracture to 0°-5°, 40.0% 5.9% < 0.001
% (n) (28/70) (2/34)
Percentage of joints with baseline
contractures less than or equal
to 40° achieving 0°-5°, % (n) 80.9% - N/A*
Percentage of joints with baseline
contractures > 40° achieving 0°-5°,
% (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° 4.7° < 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° 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®
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 Information: 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