Ipsen today announced that the U.S. Food and Drug Administration (FDA) has approved its supplemental Biologics License Application (sBLA) for Dysport® (abobotulinumtoxinA) for the treatment of upper limb spasticity in adult patients after the submission of the dossier in September 2014. Dysport® is now approved for the treatment of upper limb spasticity in adult patients, to decrease the severity of increased muscle tone in elbow flexors, wrist flexors and finger flexors. Clinical improvement may be expected one week after administration of Dysport®. A majority of patients in clinical studies were retreated between 12 and 16 weeks; some patients had a duration of response as long as 20 weeks. In Europe, regulatory procedures are in progress for strengthening the existing upper limb spasticity label indication of Dysport® to include key medical data such as muscle dose recommendations, treatment intervals, efficacy data and safety updates.
Marc de Garidel, Ipsen’s Chairman and CEO, stated: “We are pleased with the FDA approval of Dysport® in the treatment of upper limb spasticity in adults in the United States. This differentiated label is a testimony to the quality of the clinical data. Ipsen has reinforced its commercial capacity and is now prepared to start commercialization of Dysport® in this new indication in the US. This launch represents a major step forward in our ambition to become a global leader in treating patients with spasticity.”
“The FDA approval of Dysport® provides a new therapeutic option to help adults living with spasticity” said Allison Brashear, M.D., Professor and Chair of Neurology, Wake Forest Baptist Medical Center and the U.S. principal investigator of the Phase III trial. “This approval is based on strong clinical data which showed that Dysport® improved muscle tone in the upper limb essential for active use of the hand and arm. It is important to realize that early identification is critical for patients with upper limb spasticity, given that when left untreated, spasticity can result in increased muscle tone.”
About the Approval
The approval was based on a rigorous development program that included clinical trials conducted in over 600 patients. In the Phase III pivotal study, 238 adult patients with upper limb spasticity participated in the study for up to one year. The international, multi-center, double-blind, randomized, placebo-controlled study compared the efficacy of Dysport® (n=159) versus placebo (n=79) in hemiparetic patients following stroke or brain trauma. The trial also included patients who were botulinum toxin naïve or previously treated with a botulinum toxin, encompassing a broad patient population. The co-primary endpoints of the study were the improvement of muscle tone in the treated upper limb measured by the Modified Ashworth Scale (MAS) versus placebo and the clinical benefit for patients as assessed by the Physician Global Assessment (PGA) versus placebo at Week 4. The trial was followed by an open-label study wherein patients received Dysport® for up to five treatment cycles to assess the long term safety.
The Phase III pivotal data showed that those treated with Dysport® demonstrated statistically significant improvement in muscle tone measured by the MAS and a significantly higher physician-rated clinical benefit measured by the PGA versus placebo at Week 4 (p≤ 0.05). At Week 4, both doses of Dysport® (Dysport® 500 units and 1000 units) significantly reduced muscle tone as measured by MAS in all primary target muscle groups, which included elbow, wrist, and finger muscles, with approximately 3 out of 4 patients1 responding to Dysport®. The most frequently reported adverse reactions (≥2%) are: urinary tract infection, nasopharyngitis, muscular weakness, musculoskeletal pain, dizziness, fall and depression. The safety profile observed in the study was consistent with the known safety profile of Dysport®, and there were no differences in the rate of serious adverse events between the treatment groups: placebo (3.7%), Dysport® 500 U (3.7%), Dysport® 1000 U (3.7%).
About Upper Limb Spasticity
It is estimated that 1.8 million adult Americans may suffer from spasticity2 3 4 5, which in the upper arm can cause muscle stiffness, flexing, spasms, twitching and pain. Upper limb spasticity (ULS) can make everyday tasks, such as washing your hands, difficult. The condition most commonly occurs after a stroke, but can also result from other injuries to the central nervous system, such as a spinal cord injury or traumatic brain injury (TBI), or occur in adults with multiple sclerosis (MS) or cerebral palsy (CP). Symptoms may not appear until months or even years after the stroke or injury but may include bent elbows or wrists, and hands clenched into fists.
Dysport® is an injectable form of botulinum toxin type A (BoNT-A), which is isolated and purified from Clostridium BoNT-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 and is licensed in more than 80 countries for various indications including: blepharospasm, hemifacial spasm, spasmodic torticollis (ST) (previously referred to as cervical dystonia), axillary hyperhidrosis, and glabellar lines. Dysport® is approved in the United States for the treatment of adults with Cervical Dystonia, for the treatment of adults with moderate to severe glabellar lines, and now the treatment of upper limb spasticity in adults.
Ipsen (ipsen.com) 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 40 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 urologyoncology. 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 and neuro-endocrine 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. Ipsen’s shares are traded on segment A of Euronext Paris (stock code: 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.
Ipsen Forward Looking Statement
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1.*MAS responders week 4: 74% to Dysport® 500 units, 79% to Dysport® 1000 units and 23% to placebo
2. "Stroke Facts." Centers for Disease Control and Prevention. Web. 10 June 2015.
3. Opheim A, et al. (2014). Upper-Limb Spasticity During the First Year After Stroke. Stroke Arm Longitudinal Study at the University of Gothenburg. American Journal of Physical Medicine & Rehabilitation, 93: 884:896.
4. "Traumatic Brain Injury in the United States: Fact Sheet." Centers for Disease Control and Prevention. 6 June 2015.
5. Ganish S, et al. (2013). Medical Comorbidities in Disorders of Consciousness Patients and Their Association with Functional Outcomes. Archives of Physical Medicine and Rehabilitation, 94: 1899-907.
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