Adults with Cervical Dystonia

Overview Efficacy Safety Dosing

XEOMIN® for Adults with Cervical Dystonia

Reduces Severity of Cervical Dystonia Symptoms, Including Abnormal Head Position and Neck Pain

XEOMIN® is indicated for the treatment of adults with cervical dystonia.1

Proven Effective in the Treatment of Adults with Cervical Dystonia

XEOMIN Efficacy vs Placebo

Compared with placebo, XEOMIN demonstrated significant improvement in Toronto Western Spasmodic compared with baseline.*1,2

Studied in nearly 600 patients with cervical dystonia in clinical trials worldwide3

Results in the 120 unit and 240 unit treatment groups were both significantly better than placebo2

Pivotal Study Design

Phase 3, multicenter, double-blind study in 233 patients from the intent-to-treat (ITT) population who were randomized to receive a single treatment of XEOMIN 240 units (n=81), XEOMIN 120 units (n=78), or placebo (n=74). Male and female patients 18 to 75 years of age were eligible if they had cervical dystonia of predominantly rotational form and a TWSTRS Total Score ≥20. Patients previously treated with botulinum toxin were eligible but only if ≥10 weeks had passed since their last injection. Patients had TWSTRS Severity Score ≥10, TWSTRS Disability Score ≥3, and TWSTRS Pain Score ≥1. Patients with swallowing disorders or any significant neuromuscular disease that might interfere with the study were excluded from enrollment. Change from baseline in total TWSTRS was the primary efficacy endpoint.2

Injection sites

Each patient received a single administration of 4.8 mL of reconstituted study agent (XEOMIN 240 units, XEOMIN 120 units, or placebo).1

The investigator at each site decided which muscles would receive injections of the study agent, the number of injection sites, and the volume at each site.

Most patients received a total of 2–10 injections into the selected muscles. Patients were assessed by telephone at 1 week post-injection, during clinic visits at weeks 4 and 8, and then by telephone assessments or clinic visits every 2 weeks up to week 20.1

Patient population

The mean age of the study patients was 53 years, and 66% of the patients were women. At study baseline, 61% of patients had previously received a botulinum toxin as treatment for cervical dystonia. The study was completed by 94% of study patients. Three patients discontinued the study prematurely due to adverse events: two patients in the 240 unit group experienced musculoskeletal pain and muscle weakness, and one patient in the 120 unit group experienced nausea and dizziness.3

Results

The primary efficacy endpoint was the change in the TWSTRS Total Score from baseline to week 4 post-injection, in the intent to treat (ITT) population, with missing values replaced by the patient’s baseline value. In the ITT population, the difference between the XEOMIN 240 unit group and the placebo group in the change of the TWSTRS Total Score from baseline to week 4 was -9.0 points, (95% confidence interval (CI) -12.0; -5.9 points); the difference between the XEOMIN 120 unit group and the placebo group in the change of the TWSTRS Total Score from baseline to week 4 was -7.5 points, (95% CI -10.4; -4.6 points).3

Comparison of each XEOMIN group with the placebo group was statistically significant at P<0.001. XEOMIN doses of 120 units and 240 units demonstrated no significant difference in effectiveness between the doses. The efficacy of XEOMIN was similar in patients who were botulinum toxin–naïve and those who had received botulinum toxin prior to this study.2

Examination of age and gender subgroups did not identify differences in response to XEOMIN. There were too few African-American patients to adequately assess efficacy in that population.2

Efficacy of XEOMIN vs Active Comparator (Botox®)

XEOMIN and Botox were similarly effective in treating the symptoms of cervical dystonia as measured by TWSTRS score at week 4.4

Noninferiority Study Design

A prospective, randomized, multicenter, double-blind, active-controlled, noninferiority clinical trial using XEOMIN (n=213) or onabotulinumtoxinA (Botox; n=207). Included patients were diagnosed with cervical dystonia of the predominantly rotational form and a stable previous therapeutic response to Botox. Patients had to have a TWSTRS Severity Score of ≥10, a rotation score of ≥2, and a rotation score higher than the score for laterocollis and retrocollis. Patients were excluded if they had concomitant diseases that made an injection impossible. There were no relevant differences between treatment groups at baseline. Both groups had a median TWSTRS Severity Score of 18 points (moderate severity). The control visit was scheduled for day 28, but patients were monitored for up to 16 weeks.4

The potency units of XEOMIN are specific to the preparation and assay method used and are not interchangeable with other preparations of botulinum toxin products. Therefore, Units of biological activity of XEOMIN cannot be compared to or converted into Units of any other botulinum toxin products.

References

  1. XEOMIN® [package insert]. Raleigh, NC: Merz North America, Inc; 2018.
  2. Comella CL, Jankovic J, Truong DD, Hanschmann A, Grafe S; US XEOMIN Cervical Dystonia Study Group. Efficacy and safety of incobotulinumtoxinA (NT 201, XEOMIN®, botulinum neurotoxin type A, without accessory proteins) in patients with cervical dystonia. J Neurol Sci. 2011;308(1-2):103-109.
  3. Data on file. Raleigh, NC: Merz North America, Inc.
  4. Benecke R, Jost WH, Kanovsky P, Ruzicka E, Comes G, Grafe S. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64(11):1949-1951.