Study Participants in the Higher Dose Groups Treated with
a Single Injection of XIAFLEX® Showed Statistically
Significant Decrease in Size and Hardness of Dupuytren's Disease
Nodules, a Pre-Cursor Condition to Dupuytren's
Contracture
DUBLIN, Sept. 30, 2016 /PRNewswire/ -- Endo
Pharmaceuticals Inc., a subsidiary of Endo International plc
(NASDAQ: ENDP) (TSX: ENL), today announced new data to be presented
evaluating the safety and efficacy of
XIAFLEX®(collagenase clostridium
histolyticum) (or CCH) injection under investigation for the
treatment of palmar Dupuytren's disease nodules. The findings will
be presented during a podium presentation on Saturday, October 1, 2016 at 10:40 a.m. CDT at the annual meeting of the
American Society for Surgery of the Hand (ASSH) held from
September 29 to October 1, 2016 in
Austin, Texas.
In a Phase 2, randomized, double-blind, placebo-controlled,
dose-ranging study, in 75 adult study participants with Dupuytren's
disease and at least 1 nodule who received a single injection of
CCH 0.40 mg or 0.60 mg, a statistically significant decrease was
shown from baseline in the mean nodule surface area
(P≤0.001), consistency score (P<0.001) and
hardness score (P≤0.01) at week 8 versus study participants
receiving placebo. The safety profile of those treated with CCH was
generally well tolerated. Adverse events included extremity pain,
axillary pain, injection site-related adverse events and pruritus.
One adverse event was reported as severe (injection site pain with
CCH 0.60 mg). No patients were discontinued from the study because
of an adverse event.
The majority of study participants receiving higher doses of CCH
were satisfied with their treatment and outcomes – 88.9 percent of
18 study participants in the 0.40 mg CCH group and 83.3 percent of
18 study participants in the 0.60 mg CCH group were "very
satisfied" or "quite satisfied" with treatment at week 8 compared
to placebo. Similarly, the investigators' global assessment showed
an improvement in study participants versus placebo.
"Currently, no treatment has been approved by the U.S. Food and
Drug Administration (FDA) for palmar nodules associated with
Dupuytren's disease, although many nodules may be a pre-cursor to
full Dupuytren's contracture," said Bronier Costas, M.D.,
orthopedic surgeon at The Hand and Upper Extremity Center of
Georgia and the lead study
investigator. "These study findings could be an encouraging
indicator that treatment with agents that disrupt collagen
formation may help reduce nodule size and consistency, and merit
further investigation."
In this eight-week, double-blind trial, palpable palmar nodules
on 75 adults with Dupuytren's disease and at least 1 palmar nodule
were selected for treatment. Study participants were randomized to
receive CCH 0.25 mg (n=22), 0.40 mg, or 0.60 mg (n=18,
respectively) and then allocated to active treatment (CCH) or
placebo (n=16). A single injection into the selected nodule was
performed on Day 1. Starting at Week 1, all study participants were
instructed to massage the nodule twice daily until Week 4. Efficacy
and safety assessments were conducted throughout the study.
Investigator-reported nodular consistency and hardness were
evaluated at Weeks 1, 4, and 8. Investigator-rated patient
improvement (1 [very much improved] to 7 [very much worse]) and
patient satisfaction (1 [very satisfied] to 5 [very dissatisfied])
were assessed at week 8.
"XIAFLEX® continues to be the only FDA-approved
treatment of adult patients with Dupuytren's contracture with a
palpable cord," said Sue Hall,
Ph.D., Endo's Executive Vice President, Chief Scientific Officer
and Global Head of Research & Development and Quality. "We are
encouraged that these new data showed a beneficial effect for
patients with Dupuytren's nodules and the potential for improvement
in symptoms and discomfort. We continue to be excited by these data
and other potential indications for XIAFLEX®."
About Dupuytren's Disease
Dupuytren's disease is a
common fibroproliferative disease of the palmar fascia 1
that occurs in approximately 1% to 32% of individuals in Western
countries. 2,3 It is characterized by thickening and
shortening of fibrous cords within the hand that impact the finger
joints (particularly metacarpophalangeal and proximal
interphalangeal joints of the ring and small fingers) and while it
can start with the appearance of palmar nodules, often leads to
flexion contraction and reduced function, also known as Dupuytren's
contracture.4 Dupuytren's disease exhibits
3 clinical phases known as the proliferative, contractile, and
residual phases.
About Dupuytren's Contracture (DC)
DC is a
progressive condition affecting the hand, specifically the layer of
tissue just under the skin of the palm and fingers. While this
layer of tissue normally contains collagen, in patients with DC
there is an increase in the amount of collagen produced. Abnormal
collagen buildup results in nodule and cord formation that worsens
over time. Eventually, rope-like collagen cords may form, thicken
and shorten, affecting the joints and causing the fingers to be
drawn in toward the palm. This thickening and shortening of the
Dupuytren's cord can reduce the finger joint's range of motion (how
much a person can move or straighten them). Once the Dupuytren's
collagen cord can be felt, it is referred to as a "palpable
cord."
About
XIAFLEX®
XIAFLEX® (collagenase
clostridium histolyticum, or CCH) is a biologic approved in the
U.S., EU, Canada and Australia for the treatment of
adult Dupuytren's contracture (DC) patients with a palpable cord,
and approved in the United
States for the treatment of adult men with Peyronie's
disease (PD) with a palpable plaque and penile curvature deformity
of at least 30 degrees at the start of therapy.
XIAFLEX® consists of a combination of two subtypes
of collagenase, derived from Clostridium histolyticum. Together,
the collagenase sub-types are thought to work synergistically to
break the bonds of the triple helix collagen structure.
XIAFLEX® has been granted Orphan status in the
United States by the FDA for DC and PD. Since 2010,
it is estimated that more than 80,000 patients with Dupuytren's
contracture have been treated with XIAFLEX®.
5
IMPORTANT SAFETY INFORMATION FOR XIAFLEX®
(DUPUYTREN'S CONTRACTURE)
INDICATION
XIAFLEX® is indicated for the
treatment of adult patients with Dupuytren's contracture with a
palpable cord.
IMPORTANT SAFETY INFORMATION FOR XIAFLEX®
- XIAFLEX® is contraindicated in patients with a
history of hypersensitivity to XIAFLEX® or to
collagenase used in any other therapeutic application or
application method
- In the controlled and uncontrolled portions of clinical trials
in Dupuytren's contracture, flexor tendon ruptures occurred after
XIAFLEX® injection. Injection of XIAFLEX®
into collagen-containing structures such as tendons or ligaments of
the hand may result in damage to those structures and possible
permanent injury such as tendon rupture or ligament damage.
Therefore, XIAFLEX® should be injected only into the
collagen cord with a MP or PIP joint contracture, and care should
be taken to avoid injecting into tendons, nerves, blood vessels, or
other collagen-containing structures of the hand. When injecting a
cord affecting a PIP joint of the fifth finger, the needle
insertion should not be more than 2 to 3 mm in depth and avoid
injecting more than 4 mm distal to the palmar digital crease
- Other XIAFLEX®-associated serious local adverse
reactions in the controlled and uncontrolled portions of the
studies included pulley rupture, ligament injury, complex regional
pain syndrome (CRPS), sensory abnormality of the hand, and skin
laceration (tear). In a historically controlled post-marketing
trial, the incidence of skin laceration (22%) was higher for
subjects treated with two concurrent injections of
XIAFLEX® compared with subjects treated with up to three
single injections in the placebo-controlled premarketing trials
(9%). Cases of skin laceration requiring skin graft after finger
extension procedures have been reported post-marketing. Signs or
symptoms that may reflect serious injury to the injected
finger/hand should be promptly evaluated because surgical
intervention may be required
- In the controlled portions of the clinical trials in
Dupuytren's contracture, a greater proportion of
XIAFLEX®-treated patients (15%) compared to
placebo-treated patients (1%) had mild allergic reactions
(pruritus) after up to 3 injections. The incidence of
XIAFLEX®-associated pruritus increased after more
XIAFLEX® injections in patients with Dupuytren's
contracture
- Because XIAFLEX® contains foreign proteins, severe
allergic reactions to XIAFLEX® can occur. Anaphylaxis
was reported in a post-marketing clinical study in one patient who
had previous exposure to XIAFLEX® for the treatment of
Dupuytren's contracture. Healthcare providers should be prepared to
address severe allergic reactions following XIAFLEX®
injections
- In the XIAFLEX® trials in Dupuytren's contracture,
70% and 38% of XIAFLEX®-treated patients developed an
ecchymosis/contusion or an injection site hemorrhage, respectively.
Patients with abnormal coagulation (except for patients taking
low-dose aspirin, eg, up to 150 mg per day) were excluded from
participating in these studies. Therefore, the efficacy and safety
of XIAFLEX® in patients receiving anticoagulant
medications (other than low-dose aspirin, eg, up to 150 mg per day)
within 7 days prior to XIAFLEX® administration is not
known. In addition, it is recommended to avoid use of
XIAFLEX® in patients with coagulation disorders,
including patients receiving concomitant anticoagulants (except for
low-dose aspirin)
- In the XIAFLEX® clinical trials for Dupuytren's
contracture, the most common adverse reactions reported in ≥25% of
patients treated with XIAFLEX® and at an incidence
greater than placebo were edema peripheral (eg, swelling of the
injected hand), contusion, injection site hemorrhage, injection
site reaction, and pain in the injected extremity
IMPORTANT SAFETY INFORMATION FOR XIAFLEX®
(PEYRONIE'S DISEASE)
INDICATION
XIAFLEX® is
indicated for the treatment of adult men with Peyronie's disease
with a palpable plaque and curvature deformity of at least 30
degrees at the start of therapy.
IMPORTANT SAFETY INFORMATION FOR XIAFLEX®
WARNING: CORPORAL RUPTURE (PENILE FRACTURE) OR OTHER SERIOUS
PENILE INJURY IN THE TREATMENT OF PEYRONIE'S DISEASE
Corporal rupture (penile fracture) was reported as an adverse
reaction in 5 of 1044 (0.5%) XIAFLEX®-treated patients in clinical
studies. In other XIAFLEX®-treated patients (9 of 1044; 0.9%), a
combination of penile ecchymoses or hematoma, sudden penile
detumescence, and/or a penile "popping" sound or sensation was
reported, and in these cases, a diagnosis of corporal rupture
cannot be excluded. Severe penile hematoma was also reported as an
adverse reaction in 39 of 1044 (3.7%) XIAFLEX®-treated
patients.
Signs or symptoms that may reflect serious penile injury
should be promptly evaluated to assess for corporal rupture or
severe penile hematoma which may require surgical
intervention.
Because of the risks of corporal rupture or other serious
penile injury, XIAFLEX® is available for the treatment of
Peyronie's disease only through a restricted program under a Risk
Evaluation and Mitigation Strategy (REMS) called the XIAFLEX® REMS
Program.
- XIAFLEX® is contraindicated in the treatment of Peyronie's
plaques that involve the penile urethra due to potential risk to
this structure and in patients with a history of hypersensitivity
to XIAFLEX® or to collagenase used in any other therapeutic
application or application method
- Injection of XIAFLEX® into collagen-containing structures such
as the corpora cavernosa of the penis may result in damage to those
structures and possible injury such as corporal rupture (penile
fracture). Therefore, XIAFLEX® should be injected only into the
Peyronie's plaque and care should be taken to avoid injecting into
the urethra, nerves, blood vessels, corpora cavernosa or other
collagen-containing structures of the penis
- In the double-blind, placebo-controlled portions of the
clinical trials in Peyronie's disease, a greater proportion of
XIAFLEX®-treated patients (4%) compared to placebo-treated patients
(1%) had localized pruritus after up to 4 treatment cycles
(involving up to 8 XIAFLEX® injection procedures). The incidence of
XIAFLEX®-associated pruritus was similar after each injection
regardless of the number of injections administered
- Because XIAFLEX® contains foreign proteins, severe allergic
reactions to XIAFLEX® can occur. Anaphylaxis was reported in a
post-marketing clinical trial in one patient who had previous
exposure to XIAFLEX® for the treatment of Dupuytren's contracture.
Healthcare providers should be prepared to address severe allergic
reactions following XIAFLEX® injections. The safety of more than
one treatment course of XIAFLEX® is not known
- In the XIAFLEX® controlled trials in Peyronie's disease, 65.5%
of XIAFLEX®-treated patients developed penile hematoma, and 14.5%
developed penile ecchymosis. Patients with abnormal coagulation
(except for patients taking low-dose aspirin, eg, up to 150 mg per
day) were excluded from participating in these studies. Therefore,
the efficacy and safety of XIAFLEX® in patients receiving
anticoagulant medications (other than low-dose aspirin, eg, up to
150 mg per day) within 7 days prior to XIAFLEX® administration is
not known. In addition, it is recommended to avoid use of XIAFLEX®
in patients with coagulation disorders, including patients
receiving concomitant anticoagulants (except for low-dose
aspirin)
- In the XIAFLEX® clinical trials for Peyronie's disease, the
most frequently reported adverse drug reactions (≥25%) and at an
incidence greater than placebo included: penile hematoma, penile
swelling, and penile pain
Please see the full Prescribing Information,
including Boxed Warning and Medication Guide, available
at www.XIAFLEX.com.
- Warwick D, Thomas A, Bayat A. Dupuytren's disease: overview of
a common connective tissue disease with a focus on emerging
treatment options. Int J Clin Rheumatol.
2012;7(3):309-323.
- Lanting R, Broekstra DC, Werker PM, van den Heuvel ER. A
systematic review and meta-analysis on the prevalence of Dupuytren
disease in the general population of Western countries. Plast
Reconstr Surg. 2014;133(3):593-603.
- Dibenedetti DB, Nguyen D, Zografos L, Ziemiecki R, Zhou X.
Prevalence, incidence, and treatments of Dupuytren's disease in
the United States: results from a
population-based study. Hand (N Y ). 2011;6(2):149-158.
- Picardo NE, Khan WS. Advances in the understanding of the
aetiology of Dupuytren's disease. Surgeon. 2012;10(3):151-158.
- Data on file. DOF-XDC-19. Endo Pharmaceuticals Inc.;
July 2016.
About Endo International plc
Endo
International plc is a global specialty pharmaceutical company
focused on improving patients' lives while creating shareholder
value. Endo develops, manufactures, markets and
distributes quality branded pharmaceutical and generic
pharmaceutical products as well as over-the-counter medications
though its operating companies. Endo has global
headquarters in Dublin, Ireland, and U.S. headquarters
in Malvern, PA. Learn more at www.endo.com.
About Endo Pharmaceuticals Inc.
Endo
Pharmaceuticals Inc. is focused on developing and delivering
high-value branded pharmaceutical products that meet the unmet
needs of patients. Endo Pharmaceuticals is an
operating company of Endo International plc (NASDAQ:
ENDP) (TSX: ENL), a global specialty pharmaceutical company focused
on improving patients' lives while creating shareholder value.
Learn more at www.endo.com or www.endopharma.com.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains "forward-looking
statements," including but not limited to the statements by Drs.
Costas and Hall, as well as statements regarding the safety,
efficacy, market and product potential, and other statements
regarding XIAFLEX®. These statements are based on
current expectations of future events. If underlying assumptions
prove inaccurate or unknown risks or uncertainties materialize,
actual results could vary materially
from Endo's expectations and projections. Risks and
uncertainties include, among other things, general industry and
pharmaceutical market conditions; technological advances and
patents attained by competitors; challenges inherent in the
research and development process; challenges related to new product
marketing, such as the unpredictability or market acceptance for
new pharmaceutical products and new indications for such products;
and governmental laws and regulations affecting domestic and
foreign operations. Endo expressly disclaims any intent
or obligation to update these forward-looking statements except as
required by law. Additional information concerning these and other
risks can be found in press releases issued by Endo, as well
as in Endo's public filings with the U.S. Securities
and Exchange Commission and Canadian securities regulators,
including the discussion under the heading "Risk Factors"
in Endo's Annual Report on Form 10-K and any subsequent
Quarterly Reports on Form 10-Q. Copies of Endo's press
releases and additional information about Endo are
available at www.endo.com.
XIAFLEX is a registered trademark of Endo Global
Ventures.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/endo-pharmaceuticals-presents-new-phase-2-data-evaluating-the-safety-and-effectiveness-of-xiaflex-collagenase-clostridium-histolyticum-for-dupuytrens-disease-nodules-300337092.html
SOURCE Endo International plc