Limb Spasticity

December 4, 2017

Ipsen issued detailed results from a phase III, randomized, double-blind, placebo-controlled study (NCT01249404) and its open-label extension study (NCT01251367) of Dysport (abobotulinumtoxinA) in adult patients with lower limb spasticity following a stroke or traumatic brain injury. Patients had lower limb spasticity (Modified Ashworth Scale [MAS]) 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 (GSC) located in the calf. There was improvement in both the mean change from baseline in MAS score at the ankle joint at week four [LS mean change from baseline on MAS treatment difference vs. placebo were: -0.5 for placebo, -0.6 for Dysport 1000 Units and -0.8 for Dysport 1500 Units (p<0.05)]. The majority of patients in the study experienced a response duration of 12-16 weeks, while some experienced a longer duration of response (approximately 20 weeks). The international phase III registration study led to the FDA expanded approval of Dysport for injection for the treatment of spasticity in adults, based on its supplemental Biologics License Application (sBLA) in lower limb spasticity, on June 16, 2017. This same study has been the basis for marketing authorization in other key markets, including the U.K. and Germany, in late 2016, and regulatory procedures are still ongoing in other countries.

February 22, 2016

Ipsen released results of a phase III randomized study of Dysport in the treatment of dynamic equinus foot deformity (also known as pediatric lower limb spasticity), a condition associated with cerebral palsy in children. The study was multicenter, prospective, double-blind, randomized and placebo-controlled. It was conducted in the U.S., Mexico, Chile, Turkey, France and Poland. A total of 241 patients from 27 centers were randomized to treatment with Dysport 10U/kg/leg (n=80), Dysport 15U/kg/leg (n=80) or placebo (n=81). The purpose of this study was to assess the efficacy of Dysport compared to placebo in the treatment of Lower Limb Spasticity in children with cerebral palsy. Muscle tone and spasticity were assessed using the Modified Ashworth Scale (MAS) and the Tardieu Scale; patient functionality was assessed using the Physician’s Global Assessment (PGA) and goal attainment scaling (GAS). Study results showed a significant improvement v. placebo on muscle tone at both doses at week four post-injection with abobotulinumtoxinA; mean [95%CI] treatment differences v. placebo were: -0.49 [-0.75, -0.23] (p=0.0002) for 15U/kg/leg and -0.38 [-0.64, -0.13] (p=0.003) for 10U/kg/leg.

September 14, 2015

Ipsen issued results of a phase III study of Dysport in post-stroke or traumatic brain injury patients with upper limb spasticity. The multicenter, prospective, double blind, randomized, placebo-controlled, global trial enrolled 243 patients randomized to treatment with Dysport 500U (n=80), Dysport 1000U (n=79) or placebo (n=79). Results 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 v. placebo), and –1.4 (1.1) in the Dysport 1000 U group (p<0.0001 v. 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 v. placebo), and 1.8 (1.1) in the Dysport 1000 U group (p<0.0001 v. placebo). The mean change from baseline at week 4 in Disability Assessment Scale (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 v. placebo), and –0.7 (0.7) in the Dysport 1000 U group (p=0.0772 v. placebo).

August 24, 2015

Merz Neurosciences has issued results of a phase III study of incobotulinumtoxinA for post-stroke upper limb spasticity. The trial was a prospective, multicenter, randomized, doubleblind, placebo-controlled main period (12-week duration) with a single incobotulinumtoxinA 400 U treatment or placebo, followed by a 36-week open-label extension in which subjects (n=259) could receive up to three additional treatment cycles. The main period randomization rate of incobotulinumtoxinA to placebo was 2:1. In the primary analysis, the co-primary variables were improvements in muscle tone defined as “change in Ashworth Scale score from baseline to week four” and improvements in functional outcomes, defined as “investigator’s Global Impression of Change at the week four visit.” Both showed statistical significance, with p<0.001 and p=0.003 respectively. The trial also met a key secondary outcome measure, in which subjects with an improvement =1 on the Ashworth Scale at week four were classified as responders and showed significant improvements in disability associated with spasticity (p<0.001). Treatment-related adverse events were reported for 3.8% and 1.9% of subjects treated with incobotulinumtoxinA and placebo, respectively. Merz has submitted an sBLA to the FDA to seek approval for the use of incobotulinumtoxinA in the treatment of post-stroke upper limb spasticity and anticipates FDA action prior to the end of this calendar year.

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