Ipsen announces FDA approval of Dysport® (abobotulinumtoxinA) for the treatment of lower limb spasticity in adults

Ipsen (Euronext: IPN; ADR: IPSEY) (Ipsen) today announced that the U.S. Food and Drug Administration (FDA) has expanded the approved use of Dysport^® (abobotulinumtoxinA) for injection for the treatment of spasticity in adults, based on its supplemental Biologics License Application (sBLA) in lower limb spasticity. In July 2015, Dysport^® was approved for the treatment of upper limb spasticity in adults. In July 2016, Dysport^® was approved to treat pediatric patients with lower limb spasticity aged two and older, making it the first and only botulinum toxin that the FDA approved for this indication.

 

In a Phase III, multi-center, prospective, double-blind, randomized placebo-controlled study, adult patients treated with Dysport^® following a stroke or traumatic brain injury showed improvement in muscle tone at the ankle joint, measured by the mean change from baseline on the Modified Ashworth Scale (MAS) at Week 4. The duration of response for the majority of patients within the study was between 12-16 weeks. In this study, some patients experienced a longer duration of response (approximately 20 weeks).

 

The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose of Dysport^® and muscles to be injected. Repeat Dysport^® treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection.

 

Lower limb spasticity impacts a person’s movement. In adults, approximately one in three stroke patients, one in three patients with spinal cord injury, one in six patients with traumatic brain injury, and two in three patients with Multiple Sclerosis (MS) will develop lower limb spasticity.^1,2 Adult patients with Cerebral Palsy (CP) also commonly experience spasticity in their lower limbs.¹

 

“Adult patients who have developed spasticity as a result of a stroke, Multiple Sclerosis, Cerebral Palsy, spinal cord injury, or traumatic brain injury now have another option when seeking treatment that helps reduce the effects of the increased muscle tone in their lower extremities,” said Alexandre Lebeaut, MD, Executive Vice-President, R&D, Chief Scientific Officer, Ipsen. 

 

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.

 

“Dysport^® is currently the only botulinum toxin approved by the FDA for the treatment of spasticity in adults in upper and lower limbs and also for the treatment of lower limb spasticity in children ages two and older,” said Cynthia Schwalm, Executive Vice-President and President, North America Commercial Operations, Ipsen. “We are proud that Dysport^® is now available to support an additional population of patients— including those adults managing their spasticity associated with stroke, brain injury, spinal cord injury, Multiple Sclerosis, or Cerebral Palsy—and that Ipsen is able to provide comprehensive support offerings, including the IPSEN CARES^® patient assistance program and the C.L.I.M.B.^® injector training platform for healthcare providers.”

 

About 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.³ In adults, approximately one in three stroke patients, one in three patients with spinal cord injury, one in six patients with traumatic brain injury, and two in three patients with MS will develop lower limb spasticity.^1,2

 

Lower limb spasticity commonly involves spasticity in the gastrocnemius and soleus muscle complex located in the calf.^4,5 These calf muscles, during walking, work to raise the heel from the ground.⁴ 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.³

 

About the Phase III Study

The Phase III, multi-center, prospective, double-blind, randomized placebo-controlled study, sponsored by Ipsen, evaluated the efficacy and safety of Dysport^® for the treatment of lower limb spasticity in a population of 381 adult patients (253 received Dysport^® and 128 received placebo.) Patients had lower limb spasticity (MAS score >2 in the affected ankle joint for toxin naïve patients or MAS score >3 in the affected ankle joint for toxin non-naïve patients at least four months since the last botulinum toxin injection in the affected lower limb) and were at least six months post-stroke or post-traumatic brain injury.

 

Patients were randomized to Dysport^® 1000 Units (N=125), Dysport^® 1500 Units (N=128), or placebo (N=128) injected intramuscularly into the gastrocnemius-soleus muscle complex located in the calf. In the study, at least one additional lower limb muscle was injected, according to the clinical presentation. Some of the lower limb muscles injected during the study included: tibialis posterior, flexor digitorum longus, and/or flexor hallucis longus.

 

There was improvement in both the mean change from baseline in MAS score at the ankle joint at Week 4 [LS mean change from baseline on MAS treatment difference vs. placebo were: -0.5 for placebo, -0.6 for Dysport^® 1000 Units (NS⁶), and -0.8 for Dysport^® 1500 Units (p<0.05)].

 

The study concluded that Dysport^® 1500 Units injection resulted in a statistically significant improvement in muscle tone and spasticity at the ankle joint. The duration of response for the majority of patients within the study was between 12-16 weeks. In this study, some patients experienced a longer duration of response (approximately 20 weeks).

 

The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose of Dysport^® and muscles to be injected. Repeat Dysport^® treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection.

 

The most common adverse reactions (≥5% and greater than placebo in either Dysport^® group) in adults with lower limb spasticity for Dysport^® 1000 Units, Dysport^® 1500 Units, and Placebo, respectively, were: falls (9%, 6%, 3%), muscular weakness (2%,7%, 3%), pain in extremity (6%, 6%, 2%).  Muscular weakness was reported more frequently in women (10%) treated with 1500 Units of Dysport^® compared to men (5%).

 

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 spasticity in adult patients. Dysport^® is also the first and only FDA-approved botulinum toxin for the treatment of lower limb spasticity in pediatric patients two years of age and older.

 

The C.L.I.M.B.^® (Continuum of Learning to Improve Management with Botulinum Toxin) 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^®. Visit www.Dysport.com to learn more.

 

About IPSEN CARES^® in the United States

IPSEN CARES^® (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^® 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^® 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).