Ipsen announces publication in Pediatrics of the results of the phase III randomized study showing the efficacy and safety of Dysport® (abobotulinumtoxinA) in children with dynamic equinus foot deformity due to cerebral palsy
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Single injections of both Dysport®
(abobotulinumtoxinA) doses (10U/kg/leg and 15U/kg/leg) significantly
reduce muscle hypertonia and spasticity translating into clinical and
functional benefits
PARIS–(BUSINESS WIRE)–Regulatory News:
Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the scientific
journal Pediatrics published1 the detailed results of
the phase III randomized study (NCT01249417) showing both the efficacy
and the safety of Dysport® in the treatment of dynamic
equinus foot deformity (also known as pediatric lower limb spasticity),
a condition associated with cerebral palsy in children.
The study met the primary endpoint (Modified Ashworth Scale, MAS) and
the first secondary endpoint (Physician Global Assessment, PGA) in
children with dynamic equinus foot deformity who received injections of
Dysport® in the gastrocnemius and soleus calf muscles. Dysport®
showed statistically significant improvement in muscle tone, resulting
in an improved overall clinical benefit at week 4 at the two dose levels
tested (10 and 15U/kg for unilateral injection or 20 and 30U/kg for
bilateral injections). In addition, improvement of spasticity and
attainment of overall treatment goals were demonstrated in a
statistically and clinically significant manner as compared to placebo
at week 4 after injection. Both doses of Dysport® were well
tolerated and there was no evidence of a dose relationship for adverse
events. The most frequent treatment emergent adverse events were common
childhood infections (upper respiratory tract infections).
Claude Bertrand, Executive Vice President R&D and Chief Scientific
Officer, Ipsen stated: “The peer-reviewed publication of these
Phase 3 results in the journal Pediatrics confirms the favorable
efficacy and safety profile of Dysport® in the
treatment of lower limb spasticity in children with cerebral palsy and
demonstrates improvement in functional benefit after a single injection
of Dysport®. The study results confirm the
therapeutic value of Dysport® in this
debilitating condition, the most common cause of chronic motor
disability in childhood2;3;4. ”
Professor Mauricio Delgado, Director of the Pediatric Neurology
Department at Texas Scottish Rite Hospital for Children and Professor of
Neurology and Neurotherapeutics at the University of Texas Southwestern
Medical Center) and Principal Investigator of the study stated:
“The publication of this study in Pediatrics is important news for
the field of pediatric neurorehabilitation and for the treatment of
children with equinus foot deformity due to cerebral palsy. This is the
first international study that demonstrates substantial improvements in
muscle tone and spasticity translating into clinical and functional
benefits after a single injection in this patient population. This study
both highlights the potential therapeutic value of Dysport®
(abobotulinum toxin) in children with cerebral palsy and shows the
potential value of new assessment methods that could have practical
clinical application.”
About the Double Blind Phase 3 Study in cerebral palsy (hemiplegic
and diplegic) children with lower limb spasticity
The Phase III study (NCT01249417) was multi-center, prospective, double
blind, randomized, and placebo-controlled. It was conducted in the U.S.,
Mexico, Chile, Turkey, France and Poland.
A total of 241 patients from 27 centers were randomized to treatment
with Dysport® 10U/kg/leg (n=80), Dysport®
15U/kg/leg (n=80) or placebo (n=81). The purpose of this study was to
assess the efficacy of Dysport® compared to placebo in the
treatment of Lower Limb Spasticity in children with cerebral palsy.
Muscle tone and spasticity were assessed using the MAS and the Tardieu
Scale; patient functionality was assessed using the Physician’s Global
Assessment (PGA) and goal attainment scaling (GAS).
Study results showed a significant improvement versus placebo on muscle
tone at both doses at week 4 post-injection (Primary endpoint –
Assessment scale: Modified Ashworth Scale) with abobotulinumtoxinA; mean
[95%CI] treatment differences vs. placebo were: -0.49 [-0.75, -0.23]
(p=0.0002) for 15U/kg/leg and -0.38 [-0.64, -0.13] (p=0.003) for
10U/kg/leg.
A significant improvement was also observed on the overall clinical
improvement (first secondary endpoint – Physician Global Assessment)
with mean treatment differences vs. placebo of 0.77 [0.45, 1.10] for
15U/kg/leg and 0.82 [0.50, 1.14] for 10U/kg/leg (both p<0.0001).
In addition, significant improvement in spasticity (tertiary endpoint –
using the Tardieu scale) was observed at Week 4. Both doses improved the
Tardieu scale spasticity grade Y at 4 Weeks (p<0.001). For the
15U/kg/leg dose, Week 4 improvements were also accompanied by
significant improvements in the angle of catch XV3 (p=0.0003)
and angle of arrest XV1 (p=0.01).
The use of Goal Attainment Scale clearly demonstrates that improvements
in tone and spasticity allow the patients to achieve their overall
functional goals, namely those related to walking and gait patternat
both doses tested at Week 4.
Both doses of Dysport® were well tolerated and there was no
evidence of a dose relationship for adverse events (AEs). The most
frequent TEAEs (treatment emergent adverse events) were common childhood
infections (upper respiratory tract infections). Five patients in the
abobotulinumtoxinA groups had an AE of epilepsy recorded versus none in
the placebo group, however none was considered related to study
treatment and there was an over-representation of epilepsy in the
treatment groups.
After the completion of this double blind study, patients were offered
the option to continue in an open label long-term study where they would
receive additional treatment with Dysport®.
About Dysport®
Dysport® is an injectable form of botulinum toxin type A
(BTX-A), which is isolated and purified from Clostridium BTX-A bacteria.
It is supplied as a lyophilized powder.
Dysport® was first registered for the treatment of
blepharospasm and hemifacial spasm in the United Kingdom in 1990. It is
licensed in 82 countries for various indications including
blepharospasm, upper and lower limb spasticity in adults, hemifacial
spasm, spasmodic torticollis (also referred to as cervical dystonia),
lower limb spasticity due to cerebral palsy in children, axillary
hyperhidrosis and glabellar lines.
Dysport® is approved for the treatment of lower limb
spasticity in children in many European and international markets, but
not in the United States (USA). As such, data from studies of Dysport®
in children with lower limb spasticity are investigational in the USA.
About Ipsen
Ipsen is a global specialty-driven biotechnological group with total
sales exceeding €1.2 billion in 2014. Ipsen sells more than 20 drugs in
more than 115 countries, with a direct commercial presence in 30
countries. Ipsen’s ambition is to become a leader in specialty
healthcare solutions for targeted debilitating diseases. Its development
strategy is supported by 3 franchises: neurology, endocrinology and
urology-oncology. Ipsen’s commitment to oncology is exemplified through
its growing portfolio of key therapies improving the care of patients
suffering from prostate cancer, bladder cancer or neuroendocrine tumors.
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, France; Slough/Oxford, UK; Cambridge, US). In
2014, R&D expenditure totaled close to €187 million, representing about
15% of Group sales. The Group has more than 4,500 employees worldwide.
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IPN, ISIN code: FR0010259150) and 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 trade 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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1 online at http://pediatrics.aappublications.org/content/early/2016/01/24/peds.2015-2830
2
Delgado MR, Albright AL. Movement disorders in children: definitions,
classifications, and grading systems. J Child Neurol. 2003;18
Suppl 1:S1-8.
3 Aisen ML, Kerkovich D, Mast J, et al.
Cerebral palsy: clinical care and neurological rehabilitation. Lancet
Neurol. 2011;10(9):844-852.
4 Yeargin-Allsopp M, Van
Naarden Braun K, Doernberg NS, Benedict RE, Kirby RS, Durkin MS.
Prevalence of cerebral palsy in 8-year-old children in three areas of
the United States in 2002: a multisite collaboration. Pediatrics.
2008;121(3):547-554.
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