BASKING RIDGE, N.J., Aug. 1, 2016 /PRNewswire/ — Ipsen Biopharmaceuticals, Inc., a subsidiary of Ipsen SA (Euronext: IPN; ADR: IPSEY) (Ipsen), today announced that the U.S. Food and Drug Administration (FDA) has approved its supplemental Biologics License Application (sBLA) for Dysport^® (abobotulinumtoxinA) for injection for the treatment of lower limb spasticity in pediatric patients two years of age and older. Dysport^® is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. Those treated with Dysport^® showed statistically significant improvement in co-primary efficacy assessments: mean change from baseline in Modified Ashworth scale (MAS) in ankle plantar flexor muscle tone and mean Physician’s Global Assessment (PGA) response to treatment score at Week 4 and Week 12. 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. This approval is based on a randomized, multicenter, double-blind, placebo-controlled, international Phase III pivotal study in 235 pediatric patients (158 received Dysport^® and 77 received placebo) aged 2 to 17 years with lower limb spasticity due to cerebral palsy causing dynamic equinus foot deformity.

“Pediatric lower limb spasticity is a neurological condition that is commonly seen in children with cerebral palsy, which affects the communication between the brain and the muscles, resulting in movement and posture problems,” said Cynthia Schwalm, Chief Executive Officer, Ipsen Biopharmaceuticals, Inc. “Dysport^® is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. Ipsen is committed to providing patients, their caregivers and their physicians with a comprehensive support offering, including Dysport^®, the IPSEN CARES™ patient assistance program, and the C.L.I.M.B.^® injector training platform for healthcare providers.”

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.

“This approval means that, for the first time, physicians have a FDA-approved botulinum toxin with recommended dosing guidance for the treatment of children two years of age and older with lower limb spasticity based on a large registrational study,” said Ann Tilton M.D., Professor of Clinical Neurology, Chief, Section of Child Neurology, Louisiana State University School of Medicine.

“United Cerebral Palsy (UCP) is honored to work with responsible companies, like Ipsen, to help meet the needs of people with challenging conditions such as cerebral palsy,” said Gloria Johnson-Cusack, Board Chair, United Cerebral Palsy. “Lower Iimb spasticity in pediatric patients with cerebral palsy represents a significant unmet treatment need, as there have been no FDA-approved botulinum toxin treatment options available until now. It is our hope that the work of Ipsen in this area will benefit many individual pediatric patients who struggle with lower limb spasticity.”

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, during walking, 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

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 co-primary efficacy endpoints showed a statistically significant improvement in mean change from baseline in MAS in ankle plantar flexor muscle tone at both doses of Dysport^® vs. 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: nasopharyngitis (9%, 12%,16%, 10%, 5%), upper respiratory tract infection (9%, 20%, 5%, 10%, 13%), 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.

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 Upper Limb Spasticity (ULS) in adult patients, to decrease the severity of increased muscle tone in elbow flexors, wrist flexors and finger flexors.

The C.L.I.M.B.^® (Continuum of Learning to Improve Management with Botulinum Toxin; http://www.climb-training.com^[1]) 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^®.

About IPSEN CARES^TM
IPSEN CARES^TM (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^TM 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^TM 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^[2]).

Indications and Important Safety Information

Dysport^® (abobotulinumtoxinA) for injection is indicated for the treatment of:

• Adults with upper limb spasticity, to decrease the severity of increased muscle tone in elbow flexors, wrist flexors, and finger flexors
• 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.

The safety and effectiveness of Dysport^® in the treatment of lower limb spasticity in adult patients has not been demonstrated.

IMPORTANT SAFETY INFORMATION

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.

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 (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^®.