Global regulatory submissions had been filed resulting in the US approval of Dysport® in the treatment of Adult patients with ULS and submission of variations in EU and Rest of the World countries.
Ipsen today announced that The Lancet Neurology has published online at thelancet.com/neurology the detailed results from the Ipsen sponsored phase III randomized study (NCT01313299) showing the efficacy and safety of Dysport® in post-stroke or traumatic brain injury patients with upper limb spasticity. This international phase III registration study led to the approval of Dysport® for the treatment of ULS in the US by the FDA on July 16, 2015. In Europe, the upper limb spasticity elements of the Dysport® SmPC have already been modified in some countries to include key medical data. Regulatory procedures are still ongoing in different European and Rest of World countries.
This new study met the primary endpoint (Modified Ashworth Scale, MAS) and the first secondary endpoint of Physician Global Assessment (PGA) in patients injected in different upper limb muscle groups (fingers, wrist, elbow or/and shoulder) according to patient disease presentation as Dysport® shows muscle tone reduction and clinical benefit. In addition, efficacy on active movements, spasticity, passive function and ease of applying splints was demonstrated in a statistically and clinically significant manner as compared to placebo. Efficacy was observed as early as one week post-injection and lasted up to 20 weeks in some patients.
Claude Bertrand, Executive Vice President R&D and Chief Scientific Officer, Ipsen stated: “The publication of these data in The Lancet Neurology illustrates the high quality of our study and Ipsen’s commitment to continue to improve the treatment of patients with spasticity helping them gain autonomy. It confirms the therapeutic value of Dysport® in this debilitating condition.”
Professor Jean-Michel Gracies, Neurorehabilitation, Neurology & Neurophysiology, Chairman of the Department of Physical Medicine & Rehabilitation, Groupe Hospitalier Albert CHENEVIER - Henri MONDOR (Créteil, France) stated: “The publication of this study is great news for the field of neurorehabilitation and botulinum toxin use. This is the first study that demonstrates substantial improvements in active range of motion against the injected muscles in the paretic upper limb, together with expected improvements in tone, spasticity per se, and both patient-rated and physician-rated clinical improvement after one injection only. In itself, this study both confirms the therapeutic value of abobotulinum toxin and shows the practicality and value of new assessment methods that should be used as primary outcome in future studies on the product.”
About the Double Blind Phase 3 Study conducted in Adult Upper Limb spasticity with Dysport®
The Phase III study (NCT01313299) was multi-center, prospective, double blind, randomized, and placebo-controlled. It was conducted in the U.S., France, Italy, Belgium, the Czech Republic, Poland, Slovakia, Russia and Hungary.
A total of 243 patients from 34 centers were randomized to treatment with Dysport® 500U (n=80), Dysport® 1000U (n=79) or placebo (n=79). The purpose of this study was to assess the efficacy of Dysport® compared to placebo in improving Upper Limb Spasticity in hemiparetic patients following a stroke or brain trauma. The new study results published in The Lancet Neurology showed improvements on muscle tone (MAS) with mean change in MAS score from baseline at week 4 in the Primary Targeted Muscle Group was 0.3 (SD 0.6) in the placebo group, 1.2 (1.0) in the Dysport® 500 U group (p<0.0001 vs placebo), and 1.4 (1.1) in the Dysport® 1000 U group (p<0.0001 vs placebo). On the Physician Global Assessment score, the mean change from baseline at week 4 was 0.6 (SD 1.0) in the placebo group, 1.4 (1.1) in the Dysport® 500 U group (p=0.0003 vs placebo), and 1.8 (1.1) in the Dysport® 1000 U group (p<0.0001 vs placebo). The efficacy of Dysport® was observed as early as week 1 and persisted up to 20 weeks in some patients.
The mean change from baseline at week 4 in Disability Assessment Scale (DAS) (passive function) for the principal target of treatment was 0.5 (0.7) in the placebo group (n=79), 0.7 (0.8) in the Dysport® 500 U group (p=0.2560 vs placebo), and 0.7 (0.7) in the Dysport® 1000 U group (p=0.0772 vs placebo). Significantly more patients receiving Dysport® 1000 U achieved reductions of 1 point or greater in the DAS for the principal target of treatment at weeks 4 and 12 than in the placebo group. These benefits persisted at week 12 (p=0.0002). In addition, this is the first large study of botulinum toxin A with a stepwise evaluation of spastic paresis, including active movements opposing targeted antagonists and spasticity measured by the Tardieu Scale. Tardieu Scale angles of catch (XV3) improved in finger, wrist and elbow flexors at week 4; the other Tardieu parameters (range of passive slow movement (XV1), spasticity angle (X) and spasticity grade (Y)) improved in some but not all cases at week 4. Active range of motion improved for movements opposing finger, wrist, and elbow flexors in the Dysport® 1000 U group and in finger flexors in the 500 U group. All those improvements in spasticity and function were accompanied by an improvement in the ease of applying splints by the patient after 4 weeks in the Dysport® groups compared with the placebo group. Dysport® was well tolerated at the two doses tested. After the completion of this double blind study, patients were offered the option to continue in an open label longterm study where they would receive additional treatment with Dysport® for a total of 15 months.
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 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 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 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. 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.
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