\u2013 Dysport is the first and only FDA-approved botulinum toxin for treatment of both pediatric
upper and lower limb spasticity1 \u2013
\u2013 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 \u2013
Cambridge, Mass., September 26, 2019 \u2013 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\u00ae
(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
\u201cFor 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,\u201d said Ann Tilton,
MD, study investigator and Professor of Clinical Neurology at the Louisiana State University Health
Sciences Center New Orleans. \u201cThis 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.\u201d
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\u2019s 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.
\u201cThis approval is a testament to Ipsen\u2019s legacy in neurotoxin research and continued commitment to
advancing patient care,\u201d said Kimberly Baldwin, Vice President, Franchise Head, Neuroscience
Business Unit, Ipsen. \u201cWe 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.\u201d
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 (\u22653%, 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\u00ae
(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\u00ae
(abobotulinumtoxinA) for injection is indicated for the treatment of:
\uf0b7 Lower and upper limb spasticity in adults
\uf0b7 Lower limb spasticity in pediatric patients 2 years of age and older
\uf0b7 Upper limb spasticity in pediatric patients 2 years of age and older, excluding spasticity caused by
cerebral palsy
\uf0b7 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\u2019s
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 (\u22655%): falls, muscular weakness, and pain in extremity and with
upper limb spasticity (\u22654%): muscular weakness.
Pediatric patients with lower limb spasticity (\u226510%): nasopharyngitis, cough and pyrexia and with
upper limb spasticity (\u226510%): upper respiratory tract infection and pharyngitis.
Adults with cervical dystonia (\u22655%): 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<\/p>\n\n\n\n