Ipsen Announces FDA Approval of Dysport®(abobotulinumtoxinA) for the Treatment of Upper LimbSpasticity in Children, Excluding Cerebral Palsy
– Dysport is the first and only FDA-approved botulinum toxin for treatment of both pediatric
upper and lower limb spasticity1 –
– Pivotal Phase 3 study demonstrated Dysport improved spasticity symptoms in children aged
two to 17 experiencing upper limb spasticity, as measured by the primary efficacy endpoint of
Modified Ashworth Scale at elbow or wrist flexors at Week 61 –
Cambridge, Mass., September 26, 2019 – Ipsen Biopharmaceuticals, an affiliate of Ipsen (Euronext:
IPN; ADR: IPSEY), announced today that the United States Food and Drug Administration (FDA) has
expanded the use of Dysport®
(abobotulinumtoxinA) for injection to include the treatment of upper limb
spasticity in children two years of age and older, excluding spasticity caused by cerebral palsy (CP).
This approval makes Dysport the first botulinum toxin approved by the FDA for both pediatric spasticity
indications, following the previous approval to treat children with lower limb spasticity aged two and older
received in July 2016.
1
“For physicians, it is reassuring to have a botulinum toxin treatment in Dysport which demonstrated
sustained symptom relief for spasticity, which can be physically challenging for children,” said Ann Tilton,
MD, study investigator and Professor of Clinical Neurology at the Louisiana State University Health
Sciences Center New Orleans. “This FDA decision for Dysport means we now have an approved
therapy to offer children and adolescents seeking improvements in mobility in both upper and lower
limbs.”
The approval is based on a Phase 3 study with children aged two to 17 years old being treated for upper
limb spasticity.
1 Due to Orphan Drug Exclusivity, this approval excludes use in children with upper limb
spasticity caused by CP. Dysport demonstrated statistically significant improvements from baseline at
Week 6 with doses of 8 Units/kg and 16 Units/kg vs. 2 Units/kg, as measured by the Modified Ashworth
Scale (MAS) in the elbow or wrist flexors.1 Dysport demonstrated a reduction in spasticity symptoms
through 12 weeks for most children for both upper and lower limbs.1
In the upper limb study, a majority
of patients were retreated between 16-28 weeks; however, some patients had a longer duration of
response (i.e., 34 weeks or more).
1 The most frequent adverse reactions observed were upper
respiratory tract infection and pharyngitis.
1
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.1 Those symptoms include swallowing and breathing difficulties that can be
life-threatening.1 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.1 The potency Units of Dysport are specific to the
preparation and assay method utilized.1 They are not interchangeable with other preparations of
botulinum toxin products.1 Please see below for additional Important Safety Information.
“This approval is a testament to Ipsen’s legacy in neurotoxin research and continued commitment to
advancing patient care,” said Kimberly Baldwin, Vice President, Franchise Head, Neuroscience
Business Unit, Ipsen. “We believe the data for both pediatric upper and lower limb spasticity underscore
the role of Dysport as an important treatment option for patients seeking long-lasting spasticity symptom
PRESS RELEASE
2
relief.”
Spasticity affects more than an estimated 12 million people worldwide and is a condition in which there
is an abnormal increase in muscle tone or stiffness, which may interfere with movement and particularly
impacts growing children.2,3 Treatment with injectable medications, including Dysport, have shown to be
effective in relieving the symptoms associated with spasticity in the arms and legs among children.
2
About Pediatric 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.3
Spasticity affects the muscles and joints of the extremities, and particularly impacts growing children.2
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 CP, spinal cord injury, multiple sclerosis, stroke, and brain
or head trauma.2,3
Symptoms of spasticity may include increased muscle tone, rapid muscle contractions, exaggerated
deep tendon reflexes, and/or muscle spasms.2,3 The degree of spasticity can vary from mild muscle
stiffness to severe, painful, and uncontrollable muscle spasms.3
Spasticity in children is a condition that causes muscle spasms and increased muscle stiffness in either
the upper and/or lower limbs including the elbow, wrist, finger and calf muscles.1 When muscle stiffness
in the calf is intensified, it prohibits the ankle from flexing as needed and causes the foot to be pointed
down and in.1,4
About the Phase 3 Pivotal Study
Dysport was evaluated in a Phase 3, randomized, double-blind, low-dose controlled, multicenter study
that included a total of 210 children treated, aged two to 17 years, for upper limb spasticity.
1 Patients
with a MAS of grade 2 or greater at the primary targeted muscle groups (PTMG) were enrolled and
received doses of Dysport at 8 Units/kg (n=70), 16 Units/kg (n=70) or 2 Units/kg (n=70) injected into the
PTMG (elbow flexors: brachialis and brachioradialis; wrist flexors: flexor carpi radialis, and flexor carpi
ulnaris).1 After the initial treatment, up to three further treatments of Dysport could be administered at
planned doses of either 8 Units/kg or 16 Units/kg, or titrated up or down according to investigator
judgement.1
Dysport showed statistically significant improvements from baseline in MAS in the PTMG at Week 6, the
primary endpoint, with doses of 8 Units/kg and 16 Units/kg compared to low dose Dysport (2 Units/kg) (-
2.0, -2.3 and -1.6, respectively).
1 A total of 208 patients were included in this assessment as part of the
modified intent to treat (mITT) population.1 Higher dose Dysport received a +2.0 Physician Global
Assessment (PGA) score, though there was no statistically significant difference in mean PGA (2.0, 2.0
and 1.8, respectively) or mean Goal Attainment Scale (GAS) (52.6, 52.6 and 52.1, respectively).1
In the upper limb study, a majority of patients were retreated between 16-28 weeks; however, some
patients had a longer duration of response (i.e., 34 weeks or more).1
Adverse reactions (≥3%, and reported more frequently than the control group) in pediatric patients with
upper limb spasticity for Dysport, respectively, were: upper respiratory tract infection, pharyngitis,
nausea, muscular weakness, headache, and epilepsy.
1
A pediatric assessment for Dysport demonstrates that Dysport is safe and effective in another pediatric
population. However, Dysport is not approved for such patient population due to marketing exclusivity for
another botulinum toxin.1
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.1
It is supplied as a lyophilized powder.1 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.1 Dysport is also the first and only FDA-approved botulinum toxin
for the treatment of upper and lower limb spasticity in children two years of age or older.1
3
INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
Dysport®
(abobotulinumtoxinA) for injection is indicated for the treatment of:
Lower and upper limb spasticity in adults
Lower limb spasticity in pediatric patients 2 years of age and older
Upper limb spasticity in pediatric patients 2 years of age and older, excluding spasticity caused by
cerebral palsy
Cervical dystonia in adults
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 and in approved
indications, cases of spread of effect have been reported at doses comparable to or lower than
the maximum recommended total dose.
Contraindications
Dysport is contraindicated in patients with known hypersensitivity to any botulinum toxin products, cow’s
milk protein, components in the formulation or infection at the injection site(s). Serious hypersensitivity
reactions including anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea have been
reported. If such a reaction occurs, discontinue Dysport and institute appropriate medical therapy
immediately.
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. 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
4
junction disorders (e.g., 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 CreutzfeldtJakob 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.
Most Common Adverse Reactions
Adults with lower limb spasticity (≥5%): falls, muscular weakness, and pain in extremity and with
upper limb spasticity (≥4%): muscular weakness.
Pediatric patients with lower limb spasticity (≥10%): nasopharyngitis, cough and pyrexia and with
upper limb spasticity (≥10%): upper respiratory tract infection and pharyngitis.
Adults with cervical dystonia (≥5%): muscular weakness, dysphagia, dry mouth, injection site
discomfort, fatigue, headache, musculoskeletal pain, dysphonia, injection site pain, and eye disorders.
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.
Special Populations
Use in Pregnancy
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. Based on animal data,
Dysport may cause fetal harm.
Pediatric Use
The safety and effectiveness of Dysport injected into proximal muscles of the lower limb for the
treatment of spasticity in pediatric patients has not been established. 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% vs. 6% and 4% vs. 2%, respectively).
To report SUSPECTED ADVERSE REACTIONS or product complaints, contact Ipsen at 1-855-463-
5
- You may also report SUSPECTED ADVERSE REACTIONS to the FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Please see full Prescribing Information, including Boxed Warning and Medication Guide.
About Ipsen in North America
Ipsen (Euronext: IPN; ADR: IPSEY) is a global biopharmaceutical company focused on innovation and
specialty care. The company develops and commercializes innovative medicines in three key
therapeutic areas – Oncology, Neuroscience and Rare Diseases. At Ipsen, we focus our resources,
investments and energy on discovering, developing and commercializing new therapeutic options to
provide hope for patients whose lives are challenged by difficult-to-treat diseases. Ipsen’s North
American operations are located in Cambridge, Massachusetts, one of the company’s three global hubs.
Based in the heart of Kendall Square, our fully integrated biopharmaceutical business includes
Commercial, Research & Development, Manufacturing, and Global External Innovation and Partnering.
Combined with our Canadian headquarters in Mississauga, Ontario, and other locations, Ipsen employs
approximately 600 people in North America. For more information please visit www.ipsenus.com or
www.ipsen.ca. Connect with us on Twitter and LinkedIn.
About Ipsen
Ipsen is a global specialty-driven biopharmaceutical group focused on innovation and specialty care.
The group develops and commercializes innovative medicines in three key therapeutic areas –
Oncology, Neuroscience and Rare Diseases. Its commitment to Oncology is exemplified through its
growing portfolio of key therapies for prostate cancer, neuroendocrine tumors, renal cell carcinoma and
pancreatic cancer. Ipsen also has a well-established Consumer Healthcare business. With total sales
over €2.2 billion in 2018, Ipsen sells more than 20 drugs in over 115 countries, with a direct commercial
presence in more than 30 countries. Ipsen’s R&D is focused on its innovative and differentiated
technological platforms located in the heart of the leading biotechnological and life sciences hubs (ParisSaclay, France; Oxford, UK; Cambridge, US). The Group has about 5,700 employees worldwide. Ipsen
is listed in Paris (Euronext: IPN) and in the United States through a Sponsored Level I American
Depositary Receipt program (ADR: IPSEY). For more information on Ipsen, visit www.ipsen.com.
Forward-Looking Statement
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 uncertainties that may cause actual results, performance or events to differ materially from
those anticipated herein. All of the above risks could affect the Group’s future ability to achieve its
financial targets, which were set assuming reasonable macroeconomic conditions based on the
information available today. Use of the words “believes”, “anticipates” and “expects” and similar
expressions are intended to identify forward-looking statements, including the Group’s expectations
regarding future events, including regulatory filings and determinations, and the outcome of this study or
other studies. Moreover, the targets described in this document were prepared without taking into
account external growth assumptions and potential future acquisitions, which may alter these
parameters. These objectives are based on data and assumptions regarded as reasonable by the
Group. These targets depend on conditions or facts likely to happen in the future, and not exclusively on
historical data. Actual results may depart significantly from these targets given the occurrence of certain
risks and uncertainties, notably the fact that a promising product in early development phase or clinical
trial may end up never being launched on the market or reaching its commercial targets, notably for
regulatory or competition reasons. The Group must face or might face competition from generic products
that might translate into a loss of market share. Furthermore, the Research and Development process
involves several stages each of which involves the substantial risk that the Group may fail to achieve its
objectives and be forced to abandon its efforts with regards to a product in which it has invested
significant sums. Therefore, the Group cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be
sufficient to demonstrate the safe and effective nature of the product concerned. There can be no
guarantees a product will receive the necessary regulatory approvals or that the product will prove to be
commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties
materialize, actual results may differ materially from those set forth in the forward-looking statements.
Other risks and uncertainties include but are not limited to, general industry conditions and competition;
general economic factors, including interest rate and currency exchange rate fluctuations; the impact of
6
pharmaceutical industry regulation and health care legislation; global trends toward health care cost
containment; technological advances, new products and patents attained by competitors; challenges
inherent in new product development, including obtaining regulatory approval; the Group’s ability to
accurately predict future market conditions; manufacturing difficulties or delays; financial instability of
international economies and sovereign risk; dependence on the effectiveness of the Group’s patents and
other protections for innovative products; and the exposure to litigation, including patent litigation, and/or
regulatory actions. The Group also depends on third parties to develop and market some of its products
which could potentially generate substantial royalties; these partners could behave in such ways which
could cause damage to the Group’s activities and financial results. The Group cannot be certain that its
partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A
default by any of the Group’s partners could generate lower revenues than expected. Such situations
could have a negative impact on the Group’s business, financial position or performance. The Group
expressly disclaims any obligation or undertaking to update or revise any forward-looking statements,
targets or estimates contained in this press release to reflect any change in events, conditions,
assumptions or circumstances on which any such statements are based, unless so required by
applicable law. The Group’s business is subject to the risk factors outlined in its registration documents
filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not
exhaustive and the reader is advised to refer to the Group’s 2018 Registration Document available on its
website (www.ipsen.com).
For further information:
Maryann Quinn
Director, Product Communications
Tel: +1-857-529-1151
E-mail: maryann.quinn@ipsen.com
DYSPORT is a registered trademark of Ipsen Biopharm Limited
©2019 Ipsen Biopharmaceuticals, Inc.
September 2019 DYS-US-004024
1 Dysport (abobotulinumtoxinA) [Prescribing Information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc;
September 2019.
2 American Association of Neurological Surgeons. Spasticity page. http://www.aans.org/Patients/NeurosurgicalConditions-and-Treatments/Spasticity. Accessed September 16, 2019.
3 National Institute of Neurological Disorders and Stroke. Spasticity Information Page.
https://www.ninds.nih.gov/Disorders/All-Disorders/Spasticity-Information-Page. Accessed September 16, 2019.
4 Delgado MR, Tilton A, Russman B, et al. (2016). AbobotulinumtoxinA for Equinus Foot Deformity in Cerebral
Palsy: A Randomized Controlled Trial. Pediatrics. 2016;137(2);1-9.
