XEOMIN® is indicated for the treatment of adults with cervical dystonia.1
Compared with placebo, XEOMIN demonstrated significant improvement in Toronto Western Spasmodic compared with baseline.*1,2
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
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
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
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
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.
XEOMIN® (incobotulinumtoxinA) for injection, for intramuscular or intraglandular use, is a prescription medicine that is used to treat adults with:
See full prescribing information for complete BOXED WARNING.
The effects of XEOMIN and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults, particularly in those patients who have underlying conditions that would predispose them to these symptoms.
Chronic Sialorrhea: The most commonly observed adverse reactions (incidence ≥3% of patients and greater than placebo) for XEOMIN were tooth extraction (5%), dry mouth (4%), diarrhea (4%), hypertension (4%), fall (3%), bronchitis (3%), dysphonia (3%), back pain (3%) and dry eye (3%).
Upper Limb Spasticity: The most commonly observed adverse reactions (incidence ≥2% of patients and greater than placebo) for XEOMIN were seizure (3%), nasopharyngitis (2%), dry mouth (2%), and upper respiratory tract infection (2%).
Cervical Dystonia: The most commonly observed adverse reactions (incidence ≥5% of patients and greater than placebo) for XEOMIN 120 Units and XEOMIN 240 Units, respectively, were: dysphagia (13%, 18%), injection pain site (9%, 4%), neck pain (7%, 15%), muscle weakness (7%, 11%), and musculoskeletal pain (7%, 4%).
Blepharospasm: The most commonly observed adverse reactions (incidence ≥5% of patients and twice greater than placebo) for XEOMIN were eyelid ptosis (19%), dry mouth (16%), dry eye (16%), visual impairment (12%), diarrhea (8%), headache (7%), dyspnea (5%) and nasopharyngitis (5%).
Co-administration of XEOMIN and aminoglycoside antibiotics or other agents interfering with neuromuscular transmission, e.g., tubocurarine-type muscle relaxants, should only be performed with caution as these agents may potentiate the effect of the toxin.
Use of anticholinergic drugs after administration of XEOMIN may potentiate systemic anticholinergic effects. The effect of administering different botulinum toxin products at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.
There are no adequate data on the developmental risk associated with the use of XEOMIN in pregnant women. XEOMIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Safety and effectiveness of XEOMIN in patients less than 18 years of age have not been established.
Please see accompanying full Prescribing Information, including BOXED WARNING.