AbobotulinumtoxinA Proves Effective Across Multiple Therapeutic Uses

Today, at the 70^th Nnnual Meeting of the American Academy of Neurology (AAN), Ipsen Biopharmaceuticals Inc will present data regarding abobotulinumtoxinA (Dysport) across multiple therapeutic uses.

AbobotulinumtoxinA, a lyophilized powder to be administered intravenously, is isolated and purified from Clostridium bacteria.¹

The first presentation will include a safety analysis of pooled data of abobotulinumtoxinA for pediatric lower limb (PLL) spasticity in patients 2 years to 17 years old (as well as nearly 200 children aged 2 years to 5 years); the second presentation will include an evaluation of Physician’s Global Assessment (PGA) response to repeated abobotulinumtoxinA injections in adult lower limb (ALL) spasticity; and the third presentation will include data on the persistence of therapeutic benefits after a single injection cycle of abobotulinumtoxinA on the clinical symptoms of cervical dystonia (CD) in adults. Five additional posters will be presented at the meeting.

The first presentation regarding PLL patients will display results that show consistency in the safety profile of abobotulinumtoxinA across age groups. Common childhood illnesses were related to the most adverse events (AEs). The preschool group included 299 children aged two to five years (abobotulinumtoxinA=195; placebo=104), the elementary school group included 134 children aged 6 years to 9 years (abobotulinumtoxinA=87; placebo=47) and the middle/high school group includes 43 children aged 10+ years (abobotulinumtoxinA=30; placebo=13).²

One database was formed from individual AE data from each study.

Rates of treatment emergent adverse events (TEAEs) of abobotulinumtoxinA versus placebo included: preschool (60.5% vs. 52.9%), elementary school (58.6% vs. 36.2%), middle/high school (40.0% vs. 46.2%). Rates of TEAEs considered related to abobotulinumtoxinA treatment were low across all age groups: preschool (14.9% vs. 8.7%), elementary school (11.5% vs. 2.1%), middle/high school (6.7% vs. 15.4%). The only premature study withdrawal was due to the only serious TEAE considered to be treatment related. The TEAE occurred in the middle/high school group and involved moderate muscle pain and weakness in the 30 U/kg group.

The second presentation regarding ALL spasticity showed results form a Phase 3, randomized, placebo-controlled study evaluating the PGA of treatment response after repeated injections of abobotulinumtoxinA in traumatic brain injury or stroke patients with ALL spasticity. The study had a double-blind, single-cycle phase (n = 388) and an open-label (OL) multicycle extension. The mean PGA score (a nine-point ordinal scale from −4 (markedly worse) to +4 (markedly improved) that is a commonly used scale for evaluating treatment response in clinical trials with botulinum toxins) increased at week 4 across treatment cycles with both BoNT-A 1000U and 1500U (+1.0 in the double-blind phase [double-blind placebo group: +0.7] to +1.8 and +1.9 in cycle 4 of the OL extension for 1000U and 1500U, respectively).³

The proportion of responders (PGA score of ≥ +1) treated with abobotulinumtoxinA 1000U and 1500U increased from 58.0% and 62.5%, respectively, at week 4 of the double-blind phase (double-blind placebo group: 49.2%) to 86.4% and 96.1%, respectively, at week 4 of cycle 4. The maximum clinical benefit (as measured by the PGA) was obtained after repeated dosing of abobotulinumtoxinA in the lower extremity. Using the most effective dosing regimen in adult post-stroke or traumatic brain injury patients was confirmed by the latter results.

The third presentation regarding data on the clinical symptoms of cervical dystonia will show results from a meta-analysis that studied the impact of one injection cycle of abobotulinumtoxinA. The analysis consists of 2 observational international studies and 1 registry (from the United States). Previous botulinum toxin treatment was administered in the majority (84.4%) of participants. At the baseline/first injection and at the end of the cycle/next injection, assessments were performed. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui tremor scores comprised the clinical efficacy assessments.³

Between visit 1 and visit 2 of evaluated patients, 73.9% had an injection interval of 12-16 weeks, and 23.1% had an interval of more than 16 weeks. In TWSTRS total, persistent improvements between injection visits were noted, such as disability, pain scores, severity, and the proportion of patients categorized as having severe tremors associated with CD decreased between injections.

However, while abobotulinumtoxinA has shown efficacy, multiple safety warnings come with the drug, including swallowing and breathing difficulties that can be life-threatening.

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References:

1. Ipsen Announces Efficacy and Safety Data for Dysport (abobotulinumtoxinA) Across Multiple Therapeutic Uses at the 2018 Annual Meeting of the American Academy of Neurology. https://www.businesswire.com/news/home/20180423005736/en/Ipsen-Announces-Efficacy-Safety-Data-Dysport%C2%AE-abobotulinumtoxinA. Accessed April 23, 2018.
2. Safety profile of abobotulinumtoxinA (Dysport®) for lower limb spasticity: Pooled analysis of controlled clinical trials. https://submissions.mirasmart.com/Verify/AAN2018/submission/temp/rad9F675.pdf. Accessed April 23, 2018.
3. Efficacy and safety of abobotulinumtoxinA in spastic lower limb. http://n.neurology.org/content/early/2017/11/01/WNL.0000000000004687. Accessed April 23, 2018.
4. Multicenter observational study of abobotulinumtoxinA neurotoxin in cervical dystonia: The ANCHOR-CD registry. https://www.sciencedirect.com/science/article/pii/S0022510X17301387. Accessed April 23, 2018.