Spasticity may affect adults who suffer from stroke, traumatic brain
injury, spinal cord injury, multiple sclerosis, and cerebral palsy
PARIS–(BUSINESS WIRE)– class= »bwalignl »>
Regulatory News:
Ipsen (Euronext: IPN; ADR: IPSEY) (Ipsen) today announced that the U.S.
Food and Drug Administration (FDA) has expanded the approved use of
Dysport® (abobotulinumtoxinA) for injection for the treatment
of spasticity in adults, based on its supplemental Biologics License
Application (sBLA) in lower limb spasticity. In July 2015, Dysport®
was approved for the treatment of upper limb spasticity in adults. In
July 2016, Dysport® was approved to treat pediatric patients
with lower limb spasticity aged two and older, making it the first and
only botulinum toxin that the FDA approved for this indication.
In a Phase III, multi-center, prospective, double-blind, randomized
placebo-controlled study, adult patients treated with Dysport®
following a stroke or traumatic brain injury showed improvement in
muscle tone at the ankle joint, measured by the mean change from
baseline on the Modified Ashworth Scale (MAS) at Week 4. The duration of
response for the majority of patients within the study was between 12-16
weeks. In this study, some patients experienced a longer duration of
response (approximately 20 weeks).
The degree and pattern of muscle spasticity at the time of re-injection
may necessitate alterations in the dose of Dysport® and
muscles to be injected. Repeat Dysport® treatment should be
administered when the effect of a previous injection has diminished, but
no sooner than 12 weeks after the previous injection.
Lower limb spasticity impacts a person’s movement. In adults,
approximately one in three stroke patients, one in three patients with
spinal cord injury, one in six patients with traumatic brain injury, and
two in three patients with Multiple Sclerosis (MS) will develop lower
limb spasticity.1,2 Adult patients with Cerebral Palsy (CP)
also commonly experience spasticity in their lower limbs.1
“Adult patients who have developed spasticity as a result of a
stroke, Multiple Sclerosis, Cerebral Palsy, spinal cord injury, or
traumatic brain injury now have another option when seeking treatment
that helps reduce the effects of the increased muscle tone in their
lower extremities,” said Alexandre Lebeaut, MD, Executive
Vice-President, R&D, Chief Scientific Officer, Ipsen.
Dysport® and all botulinum toxin products have a Boxed
Warning which states that the effects of the botulinum toxin may spread
from the area of injection to other areas of the body, causing symptoms
similar to those of botulism. Those symptoms include swallowing and
breathing difficulties that can be life-threatening. Dysport®
is contraindicated in patients with known hypersensitivity to any
botulinum toxin preparation or to any of the components; or in the
presence of infection at the proposed injection site(s); or in patients
known to be allergic to cow’s milk protein. The potency Units of Dysport®
are specific to the preparation and assay method utilized. They are not
interchangeable with other preparations of botulinum toxin products.
Please see below for additional Important Safety Information.
“Dysport® is currently the only botulinum
toxin approved by the FDA for the treatment of spasticity in adults in
upper and lower limbs and also for the treatment of lower limb
spasticity in children ages two and older,” said Cynthia Schwalm,
Executive Vice-President and President, North America Commercial
Operations, Ipsen. “We are proud that Dysport®
is now available to support an additional population of patients—
including those adults managing their spasticity associated with stroke,
brain injury, spinal cord injury, Multiple Sclerosis, or Cerebral
Palsy—and that Ipsen is able to provide comprehensive support offerings,
including the IPSEN CARES® patient assistance
program and the C.L.I.M.B.® injector training
platform for healthcare providers.”
About Spasticity
Spasticity is a condition in which there is an abnormal increase in
muscle tone or stiffness in one or more muscles, which might interfere
with movement. Spasticity is usually caused by damage to nerve pathways
in the brain or spinal cord that control muscle movement, and may occur
in association with cerebral palsy, spinal cord injury, multiple
sclerosis, stroke, and brain or head trauma.3 In adults,
approximately one in three stroke patients, one in three patients with
spinal cord injury, one in six patients with traumatic brain injury, and
two in three patients with MS will develop lower limb spasticity.1,2
Lower limb spasticity commonly involves spasticity in the gastrocnemius
and soleus muscle complex located in the calf.4,5 These calf
muscles, during walking, work to raise the heel from the ground.4
Symptoms of spasticity may include increased muscle tone,
rapid muscle contractions, exaggerated deep tendon reflexes, and/or
muscle spasms. The degree of spasticity can vary from mild muscle
stiffness to severe, painful, and uncontrollable muscle spasms.3
About the Phase III Study
The Phase III, multi-center, prospective, double-blind, randomized
placebo-controlled study, sponsored by Ipsen, evaluated the efficacy and
safety of Dysport® for the treatment of lower limb spasticity
in a population of 381 adult patients (253 received Dysport®
and 128 received placebo.) Patients had lower limb spasticity (MAS score
>2 in the affected ankle joint for toxin naïve patients or MAS score >3
in the affected ankle joint for toxin non-naïve patients at least four
months since the last botulinum toxin injection in the affected lower
limb) and were at least six months post-stroke or post-traumatic brain
injury.
Patients were randomized to Dysport® 1000 Units (N=125),
Dysport® 1500 Units (N=128), or placebo (N=128) injected
intramuscularly into the gastrocnemius-soleus muscle complex located in
the calf. In the study, at least one additional lower limb muscle was
injected, according to the clinical presentation. Some of the lower limb
muscles injected during the study included: tibialis posterior, flexor
digitorum longus, and/or flexor hallucis longus.
There was improvement in both the mean change from baseline in MAS score
at the ankle joint at Week 4 [LS mean change from baseline on MAS
treatment difference vs. placebo were: -0.5 for placebo, -0.6 for Dysport®
1000 Units (NS6), and -0.8 for Dysport® 1500 Units
(p<0.05)].
The study concluded that Dysport® 1500 Units injection
resulted in a statistically significant improvement in muscle tone and
spasticity at the ankle joint. The duration of response for the majority
of patients within the study was between 12-16 weeks. In this study,
some patients experienced a longer duration of response (approximately
20 weeks).
The degree and pattern of muscle spasticity at the time of re-injection
may necessitate alterations in the dose of Dysport® and
muscles to be injected. Repeat Dysport® treatment should be
administered when the effect of a previous injection has diminished, but
no sooner than 12 weeks after the previous injection.
The most common adverse reactions (≥5% and greater than placebo in
either Dysport® group) in adults with lower limb spasticity
for Dysport® 1000 Units, Dysport® 1500 Units, and
Placebo, respectively, were: falls (9%, 6%, 3%), muscular weakness
(2%,7%, 3%), pain in extremity (6%, 6%, 2%). Muscular weakness was
reported more frequently in women (10%) treated with 1500 Units of
Dysport® compared to men (5%).
About Dysport® (abobotulinumtoxinA) for
Injection
Dysport® is an injectable form of botulinum toxin type A
(BoNT-A), which is isolated and purified from Clostridium bacteria
producing BoNT-A. It is supplied as a lyophilized powder. Dysport®
has approved indications in the United States for the treatment of
adults with Cervical Dystonia (CD) and for the treatment of spasticity
in adult patients. Dysport® is also the first and only
FDA-approved botulinum toxin for the treatment of lower limb spasticity
in pediatric patients two years of age and older.
The C.L.I.M.B.® (Continuum of Learning
to Improve Management
with Botulinum Toxin) injector
training platform is a multi-tiered learning continuum designed to
educate physicians with every level of experience with botulinum toxin
therapy. C.L.I.M.B.® can help physicians improve their
clinical skills involving the appropriate use of Dysport®.
Visit www.Dysport.com
to learn more.
About IPSEN CARES® in the United States
IPSEN CARES® (Coverage, Access, Reimbursement, &
Education Support) is dedicated to ensuring patients, providers and
caregivers have the resources needed to help access the Ipsen
medications that are critical to managing their conditions. IPSEN CARES®
is staffed Monday to Friday by experts who can assist with a broad range
of medical, educational, logistical and coverage information regarding
Ipsen medicines. Involving the entire treatment team that surrounds
patients on a daily basis, IPSEN CARES® can provide
benefits verification (research of a patient’s medical or pharmacy
benefit insurance coverage); prior authorization information; a patient
assistance program (free medications for uninsured patients); co-pay
assistance programs for eligible patients; billing and coding support;
coordination with specialty pharmacies. Additional information is also
available by visiting (http://www.ipsencares.com).
INDICATIONS AND IMPORTANT SAFETY INFORMATION (United States)
INDICATIONS
Dysport® (abobotulinumtoxinA) for injection is
indicated for the treatment of:
- Spasticity in adult patients
- Adults with cervical dystonia
- Lower limb spasticity in pediatric patients 2 years of age and older.
The safety and effectiveness of Dysport® injected into upper
limb muscles or proximal muscles of the lower limb for the treatment of
spasticity in pediatric patients has not been established.
Safety and effectiveness in pediatric patients with lower limb
spasticity below 2 years of age have not been evaluated.
Safety and effectiveness in pediatric patients with cervical dystonia or
upper limb spasticity have not been established.
IMPORTANT SAFETY INFORMATION
Warning: Distant Spread of Toxin Effect
Postmarketing reports indicate that the effects of Dysport® and
all botulinum toxin products may spread from the area of injection to
produce symptoms consistent with botulinum toxin effects. These may
include asthenia, generalized muscle weakness, diplopia, blurred vision,
ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and
breathing difficulties. These symptoms have been reported hours to weeks
after injection. Swallowing and breathing difficulties can be life
threatening and there have been reports of death. The risk of symptoms
is probably greatest in children treated for spasticity, but symptoms
can also occur in adults treated for spasticity and other conditions,
particularly in those patients who have underlying conditions that would
predispose them to these symptoms. In unapproved uses, including upper
limb spasticity in children, and in approved indications, cases of
spread of effect have been reported at doses comparable to lower than
the maximum recommended total dose.
Contraindications
Dysport® is contraindicated in patients with known
hypersensitivity to any botulinum toxin preparation or to any of the
components; or in the presence of infection at the proposed injection
site(s); or in patients known to be allergic to cow’s milk protein.
Hypersensitivity reactions including anaphylaxis have been reported.
Warnings and Precautions
Lack of interchangeability between botulinum toxin products
The potency Units of Dysport® are specific to the preparation
and assay method utilized. They are not interchangeable with other
preparations of botulinum toxin products, and, therefore, units of
biological activity of Dysport® cannot be compared to or
converted into units of any other botulinum toxin products assessed with
any other specific assay method.
Dysphagia and Breathing Difficulties
Treatment with Dysport® and other botulinum toxin products
can result in swallowing or breathing difficulties. Patients with
pre-existing swallowing or breathing difficulties may be more
susceptible to these complications. In most cases, this is a consequence
of weakening of muscles in the area of injection that are involved in
breathing or swallowing. When distant side effects occur, additional
respiratory muscles may be involved (see Boxed Warning). Deaths as a
complication of severe dysphagia have been reported after treatment with
botulinum toxin. Dysphagia may persist for several weeks, and require
use of a feeding tube to maintain adequate nutrition and hydration.
Aspiration may result from severe dysphagia and is a particular risk
when treating patients in whom swallowing or respiratory function is
already compromised. Patients treated with botulinum toxin may require
immediate medical attention should they develop problems with
swallowing, speech, or respiratory disorders. These reactions can occur
within hours to weeks after injection with botulinum toxin.
Pre-existing Neuromuscular Disorders
Individuals with peripheral motor neuropathic diseases, amyotrophic
lateral sclerosis, or neuromuscular junction disorders (eg, myasthenia
gravis or Lambert-Eaton syndrome) should be monitored particularly
closely when given botulinum toxin. Patients with neuromuscular
disorders may be at increased risk of clinically significant effects
including severe dysphagia and respiratory compromise from typical doses
of Dysport®.
Human Albumin and Transmission of Viral Diseases
This product contains albumin, a derivative of human blood. Based on
effective donor screening and product manufacturing processes, it
carries an extremely remote risk for transmission of viral diseases and
variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk
for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk
actually exists, the risk of transmission would also be considered
extremely remote. No cases of transmission of viral diseases, CJD, or
vCJD have ever been identified for licensed albumin or albumin contained
in other licensed products.
Intradermal Immune reaction
The possibility of an immune reaction when injected intradermally is
unknown. The safety of Dysport® for the treatment of
hyperhidrosis has not been established. Dysport® is approved
only for intramuscular injection.
Adverse reactions
Most common adverse reactions (≥2% and greater than placebo in either
Dysport® group) in adults with upper limb spasticity for
Dysport® 500 Units, Dysport® 1000 Units, and
Placebo, respectively, were: nasopharyngitis (4%, 1%, 1%), urinary tract
infection (3%, 1%, 2%), muscular weakness (2%, 4%, 1%), musculoskeletal
pain (3%, 2%, 2%), dizziness (3%, 1%, 1%), fall (2%, 3%, 2%), and
depression (2%, 3%, 1%).
Most common adverse reactions (≥ 5% and greater than placebo in either
Dysport® group) in adults with lower limb spasticity for Dysport® 1000
Units, Dysport® 1500 Units, and Placebo, respectively, were: falls (9%,
6%, 3%), muscular weakness (2%,7%, 3%), pain in extremity(6%, 6%, 2%).
Muscular weakness was reported more frequently in women (10%) treated
with 1500 units of Dysport compared to men (5%).
Most common adverse reactions (≥5% and greater than placebo) in adults
with cervical dystonia for Dysport® 500 Units and Placebo,
respectively, were: muscular weakness (16%, 4%), dysphagia (15%, 4%),
dry mouth (13%, 7%), injection site discomfort (13%, 8%), fatigue (12%,
10%), headache (11%, 9%), musculoskeletal pain (7%, 3%), dysphonia (6%,
2%), injection site pain (5%, 4%), and eye disorders (7%, 2%).
Most common adverse reactions (≥10% in any group and greater than
placebo) in pediatric patients with lower limb spasticity for Dysport®
10 Units/kg, 15 Units/kg, 20 Units/kg, or 30 Units/kg; and Placebo,
respectively, were: upper respiratory tract infection (9%, 20%, 5%, 10%,
13%), nasopharyngitis (9%, 12%,16%, 10%, 5%), influenza (0%, 10%, 14%,
3%, 8%), pharyngitis (5%, 0%,11%, 3%, 8%), cough (7%, 6%, 14%, 10%, 6%),
and pyrexia (7%, 12%, 8%, 7%, 5%).
Drug interactions
Co-administration of Dysport® and aminoglycosides or other
agents interfering with neuromuscular transmission (e.g., curare-like
agents), or muscle relaxants, should be observed closely because the
effect of botulinum toxin may be potentiated. Use of anticholinergic
drugs after administration of Dysport® may potentiate
systemic anticholinergic effects such as blurred vision. The effect of
administering different botulinum neurotoxins at the same time or within
several months of each other is unknown. Excessive weakness may be
exacerbated by another administration of botulinum toxin prior to the
resolution of the effects of a previously administered botulinum toxin.
Excessive weakness may also be exaggerated by administration of a muscle
relaxant before or after administration of Dysport®.
Use in Pregnancy
Based on animal data Dysport® may cause fetal harm. There are
no adequate and well-controlled studies in pregnant women. Dysport®
should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
Pediatric Use
Based on animal data Dysport® may cause atrophy of injected
and adjacent muscles; decreased bone growth, length, and mineral
content; delayed sexual maturation; and decreased fertility.
Geriatric Use
In general, elderly patients should be observed to evaluate their
tolerability of Dysport®, due to the greater frequency of
concomitant disease and other drug therapy. Subjects aged 65 years and
over who were treated with DYSPORT® for lower limb spasticity reported a
greater percentage of fall and asthenia as compared to those younger
(10% versus 6% and 4% versus 2%, respectively).
To report SUSPECTED ADVERSE REACTIONS or product complaints in the
United States, contact Ipsen at 1-855-463-5127. You may also report
SUSPECTED ADVERSE REACTIONS to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see Dysport® Full
Prescribing Information including Boxed Warning and Medication
Guide for the United States.
About Ipsen in North America
Ipsen Biopharmaceuticals, Inc. is the US affiliate of Ipsen, a global
specialty-driven pharmaceutical group. The US head office is located in
Basking Ridge, New Jersey. Ipsen Biopharmaceuticals Canada, Inc. is an
integrated business unit within North America and has its head office
located in Mississauga, Ontario. Ipsen Bioscience, Inc., the Ipsen US
research and development center focused on peptide research in oncology
and endocrinology, is located in Cambridge, Massachusetts. At Ipsen
Bioscience, we focus on creating a highly cooperative and passionate R&D
organization through partnerships, innovation, and continuous learning
to effectively deliver new treatments for patients. At Ipsen, we focus
our resources, investments, and energy on discovering, developing, and
commercializing new therapeutic options for oncologic, neurologic, and
endocrine diseases. For more information on Ipsen in North America,
please visit www.ipsenus.com
or www.ipsen.ca.
About Ipsen
Ipsen is a global specialty-driven pharmaceutical group with total sales
close to €1.6 billion in 2016. Ipsen sells more than 20 drugs in more
than 115 countries, with a direct commercial presence in more than 30
countries. Ipsen’s ambition is to become a leader in specialty
healthcare solutions for targeted debilitating diseases. Its fields of
expertise cover oncology, neurosciences and endocrinology (adult &
pediatric). Ipsen’s commitment to oncology is exemplified through its
growing portfolio of key therapies improving the care of patients
suffering from prostate cancer, neuro-endocrine tumors, renal cell
carcinoma and pancreatic cancer. Ipsen also has a significant presence
in primary care. Moreover, the Group has an active policy of
partnerships. Ipsen’s R&D is focused on its innovative and
differentiated technological platforms, peptides and toxins, located in
the heart of the leading biotechnological and life sciences hubs (Les
Ulis/Paris-Saclay, France; Slough/Oxford, UK; Cambridge, US). In 2016,
R&D expenditures exceeded €200 million. The Group has more than 4,900
employees worldwide. Ipsen’s shares are traded on segment A of Euronext
Paris (stock code: IPN, ISIN code: FR0010259150) and are eligible to the
“Service de Règlement Différé” (“SRD”). The Group is part of the SBF 120
index. Ipsen has implemented a Sponsored Level I American Depositary
Receipt (ADR) program, which trades on the over-the-counter market in
the United States under the symbol IPSEY. For more information on Ipsen,
visit www.ipsen.com.
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The forward-looking statements, objectives and targets contained herein
are based on the Group’s management strategy, current views and
assumptions. Such statements involve known and unknown risks and
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References
-
Martin A, et al. Epidemiological, humanistic, and economic burden of
illness of lower limb spasticity in adults: a systematic review. Neuropsychiatric
Disease and Treatment. 2014; 10 (111-122) -
Sköld A, et al. Spasticity after traumatic spinal cord injury: nature,
severity, and location. Archives of Physical Medicine and
Rehabilitation. 1999; 80 (1548-57) -
National Institute of Neurological Disorders and Stroke. Spasticity
Information Page. https://www.ninds.nih.gov/Disorders/All-Disorders/Spasticity-Information-Page
Accessed May 16, 2017. -
Gray H. Anatomy of the Human Body. “The Muscles and Fasciæ of the
Leg.” http://www.bartleby.com/107/129.html.
Accessed June 23, 2016. -
Delgado M, et al. AbobotulinumtoxinA for equinus foot deformity in
cerebral palsy: A randomized clinical trial. Pediatrics.
2016;137(2). - Not Significant
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