Ipsen, a global specialty-driven pharmaceutical group, today announced that the U.S. Food and Drug Administration (FDA) has approved Dysport® (abobotulinumtoxinA) for injection for the treatment of pediatric lower limb (PLL) spasticity in children two years of age and older.
“This approval in the US is a milestone in the treatment of pediatric lower limb spasticity, a condition that greatly impacts both children two years of age and older living with this form of spasticity and their caregivers. Dysport® is the first and only botulinum toxin approved by the FDA for this indication,” said Claude Bertrand, Executive Vice President, Research and Development, Chief Scientific Officer, Ipsen. “In our Phase 3 pivotal study, the majority of patients achieved a response lasting 16 to 22 weeks and sometimes longer. Dysport® is the only toxin to provide an FDA-approved dose range for the targeted muscles.”
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.
“The approval of abobotulinumtoxinA means that, for the first time in the USA, physicians have an FDA-approved botulinum toxin and recommended dosing and administration guidance for the treatment of children from two years of age and older with lower limb spasticity,” said Mauricio R. Delgado M.D., Professor of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center and the U.S. principal investigator of the Phase III trial. “This approval is based on data coming from worldwide studies conducted on several continents. Results were published in the journal Pediatrics1 confirming that we have conducted a pivotal study in this field. .”
1 Online at http://pediatrics.aappublications.org/content/early/2016/01/24/peds.2015-2830
About the Phase III Pivotal Study
The Phase III registrational study sponsored by Ipsen included 235 pediatric patients (158 received Dysport® and 77 received placebo; intent to treat population) and was multicenter, double-blind, prospective, randomized, and placebo-controlled. It was conducted in the U.S., Mexico, Poland, Turkey and France.
Patients were randomized (1:1:1) to Dysport® 10 Units/kg/leg, Dysport® 15 Units/kg/leg or placebo injected into the gastrocnemius-soleus muscle complex located in the calf.1 The trial included patients who were botulinum toxin naïve or previously treated with a botulinum toxin more than six months before study entry.
The study results showed a statistically significant improvement in mean change from baseline in MAS in ankle plantar flexor muscle tone at both doses of Dysport® versus placebo at Week 4 [LS mean treatment difference vs. placebo were: -0.5 for placebo, -0.9 for Dysport® 10 Units/kg/leg, and -1.0 for Dysport® 15 Units/kg/leg (p<0.05)]. Data at Week 12 as measured by the MAS was also statistically significant [LS mean treatment difference vs. placebo were: -0.5 for placebo, -0.8 for Dysport® 10 Units/kg/leg, and -1.0 for Dysport® 15 Units/kg/leg (p<0.05)]. The most common adverse reactions (≥10% of patients 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%) and pharyngitis (5%, 0%,11%, 3%, 8%), cough (7%, 6%, 14%, 10%, 6%), and pyrexia (7%, 12%, 8%, 7%, 5%).
A statistically significant improvement was also observed on the mean PGA response to treatment score at Week 4 [LS mean treatment difference of 0.7 for placebo, 1.5 for Dysport® 10 Units/kg/leg, and 1.5 for Dysport® 15 Units/kg/leg (p<0.05)]. Data at Week 12 as measured by the mean PGA response to treatment score was also statistically significant [LS mean treatment difference vs. placebo were: 0.4 for placebo, 0.8 for Dysport® 10 Units/kg/leg, and 1.0 for Dysport® 15 Units/kg/leg (p<0.05)].
A majority of patients in the clinical study were eligible for retreatment between 16 and 22 weeks; however, some had a longer duration of response. The degree and pattern of muscle spasticity and overall clinical benefit at the time of re-injection may necessitate alterations in the dose of Dysport® and muscles to be injected.
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 therapeutic indications in the United States for the treatment of adults with Cervical Dystonia (CD), the treatment of Upper Limb Spasticity (ULS) in adult patients, and now in the treatment of lower limb spasticity in children to improve tone and spasticity. The medicine was first registered in the United Kingdom in 1990 for other uses and is licensed in more than 80 countries in eight different indications, with over 1,300 peerreviewed publications.
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 lifethreatening.
About Pediatric Lower Limb 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.2
Lower limb spasticity commonly involves spasticity in the gastrocnemius and soleus muscle complex located in the calf.1,3 These calf muscles are the chief extensors of the foot at the ankle-joint. In walking, they work to raise the heel from the ground.1
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.2
1. National Institute of Neurological Disorders and Stroke. Spasticity Information Page. http://www.ninds.nih.gov/disorders/spasticity/spasticity.htm Accessed June 23, 2016.
2. Centers for Disease Control and Prevention. Prevalence of four developmental disabilities among children aged 8 years — Metropolitan Atlanta Developmental Disabilities Surveillance Program, 1996 and 2000. In: Surveillance Summaries, January 27, 2006. MMWR 2006;55(No. SS-1).
3. KidsHealth.org. Cerebral Palsy. http://kidshealth.org/en/parents/cerebral-palsy.html Accessed May 25, 2016.