XEOMIN demonstrated significant improvements in the Jankovic Rating Scale (JRS) Severity Subscore at week 6 compared with baseline and placebo.*2
Pivotal Study Design
Phase 3, multicenter, double-blind study in which 109 patients (ITT population) were randomized 2:1 to receive a single treatment with XEOMIN (n=75) or placebo (n=34). Male and female patients 18–80 years of age were eligible if they had bilateral benign essential blepharospasm previously treated with Botox, a JRS Severity Subscore ≥2, and at least 10 weeks had passed since their previous administration of onabotulinumtoxinA. Each patient in the XEOMIN group received a dose of XEOMIN that was similar to their most recent onabotulinumtoxinA injection sessions prior to study entry. The mean dose of XEOMIN was approximately 33 units per eye. Change in JRS Severity Subscore from baseline was the primary efficacy endpoint.1
* Missing values replaced with last observation carried forward.
Patients with any significant neuromuscular disease that might interfere with the study were excluded from enrollment. Patients were randomized (2:1) to receive a single administration of XEOMIN (n=75) or placebo (n=34). The mean age of the study patients was 62 years, and 65% of the patients were women.1
The study was completed by 94% of study patients. Approximately one-third of patients had other dystonic phenomena; in all but 1% this was limited to facial, cervical, perioral, and mandibular muscles. No patients discontinued the study prematurely due to adverse events.1
Each patient in the XEOMIN group received a XEOMIN treatment (dose, volume, dilution, and injection sites per muscle) that was similar to the most recent onabotulinumtoxinA injection sessions prior to study entry. The highest dose permitted in this study was 50 units per eye; the mean XEOMIN dose was 33 units per eye. Patients were assessed during clinic visits at weeks 3 and 6, and then by telephone or at clinic visits every 2 weeks up to week 20.1
The primary efficacy endpoint was the change in JRS Severity Subscore from baseline to week 6 post-injection, in the ITT population, with missing values replaced by the patient’s most recent value (ie, last observation carried forward). In the ITT population, the difference between the XEOMIN group and the placebo group in the change of the JRS Severity Subscore from baseline to week 6 was -1.0 (95% CI -1.4; -0.5) points. Comparison of the XEOMIN group with the placebo group was statistically significant at P<0.001.1
Examination of age and gender subgroups did not identify substantial differences in response to XEOMIN among these subgroups. There were too few African-American patients to assess efficacy in that population.1
In a double-blind non-inferiority trial, XEOMIN and Botox were similarly effective in treating the symptoms of blepharospasm as measured by the JRS Sum Score at week 3.4
Noninferiority Study Design
A randomized, double-blind, multicenter trial in subjects previously treated with onabotulinumtoxinA (Botox). The mean total doses of study medication injected were similar in the 2 groups (XEOMIN: 39.6 units, SD: 13.3 units; Botox: 40.8 units, SD: 14.2 units).4 Dose used was equivalent to the last 2 treatments with Botox (maximum 35 U/eye).4
Results: XEOMIN and Botox® were effective in treating blepharospasm as measured by the JRS sum score at 3 weeks. XEOMIN showed a decrease in the JRS sum score signifying an improvement in the symptoms of blepharospasm. The adjusted mean change in the JRS sum score at the control visit was -2.90 for the XEOMIN group (p<0.0001).
No patients terminated the study prematurely because of an adverse event (AE). Ptosis was the most frequently reported AE. Overall, more than 90% of AEs were of mild or moderate intensity.
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.