Xeomin (incobotulinumtoxinA)Company: Merz Pharmaceutical
Approval Status: Approved July 2010
Treatment for: cervical dystonia and blepharospasm
Xeomin is a Clostridium botulinum type - A neurotoxin complex. Clostridium botulinum toxin type A is a bacterial toxin that prevents nerves from functioning normally (a neurotoxin). It prevents nerves from releasing a chemical called acetylcholine, which is essential for the nerves to communicate with muscle cells. This toxin therefore prevents muscles from receiving nerve stimulation. Botulinum toxin type A causes muscle paralysis until such time as the nerve develops new endings to communicate with the muscles. This it is useful for treating conditions where excessive nerve stimulation to muscles is causing abnormal muscle functioning or spasms.
Xeomin is specifically indicated for adults with cervical dystonia to decrease the severity of abnormal head position and neck pain in both botulinum toxin-na?ve and previously treated patients and for the treatment of adults with blepharospasm who were previously treated with onabotulinumtoxinA (Botox).
Xeomin is supplied as a solution for intramuscular injection. The recommended initial doses are as follows:
120 Units usually injected into the sternocleidomastoid, levator scapulae, splenius capitis, scalenus, and/or the trapezius muscle(s). The dose and number of injection sites in each treated muscle should be individualized based on the number and location of the muscle(s) to be treated, the degree of spasticity/dystonia, muscle mass, body weight, and response to any previous botulinum toxin injections.
The recommended initial total dose of Xeomin should be the same dose as the patient?s previous treatment of onabotulinumtoxinA (Botox). If the previous dose of Botox is not known, the initial dose of Xeomin should be between 1.25-2.5 Units/injection site. The total dose should not exceed 70 Units (35 Units/eye).
The FDA approval of Xeomin was based on the following studies:
A randomized, double-blind, placebo-controlled, multi-center phase III trial enrolled 233 patients with cervical dystonia. The baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥20, TWSTRS severity score ≥10, TWSTRS disability score ≥3, and TWSTRS pain score ≥1. The subjects received a single administration of Xeomin 240 Units (n=81), Xeomin 120 Units (n=78), or placebo (n=74). The investigator at each site decided which muscles would receive injections of Xeomin, the number of injection sites, and the volume at each site. The primary efficacy endpoint was the change in the TWSTRS total score from baseline to Week 4 post-injection. 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; 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. Both results were statistically significant over placebo (p<0.001).
A randomized, double-blind, placebo-controlled, multi-center phase III trial enrolled 109 patients with blepharospasm. The baseline Jankovic Rating Scale (JRS) Severity subscore ≥2, and a stable satisfactory therapeutic response to previous administrations of onabotulinumtoxinA (Botox). At least 10 weeks had to have elapsed since the most recent onabotulinumtoxinA administration. The subjects were randomized to receive a single administration of Xeomin or placebo. The 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. The primary efficacy endpoint was the change in the JRS Severity subscore from baseline to Week 6 post-injection. The difference between the Xeomin arm and the placebo arm in the change of the JRS Severity subscore from baseline to Week 6 was -1.0 (p<0.001).
Adverse events associated with the use of Xeomin for cervical dystonia may include, but are not limited to, the following:
- Neck pain
- Muscle weakness
- Injection site pain
- Musculoskeletal pain
Adverse events associated with the use of Xeomin for blepharospasm may include, but are not limited to, the following:
- Eyelid ptosis
- Dry eye
- Dry mouth
- Visual impairment
- Respiratory tract infection
Mechanism of Action
Xeomin blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine from peripheral cholinergic nerve endings. This inhibition occurs according to the following sequence: neurotoxin binding to cholinergic nerve terminals, internalization of the neurotoxin into the nerve terminal, translocation of the light-chain part of the molecule into the cytosol of the nerve terminal, and enzymatic cleavage of SNAP25, a presynaptic target protein essential for the release of acetylcholine. Impulse transmission is re-established by the formation of new nerve endings.
Dressler D Botulinum toxin for treatment of dystonia. European Journal of Neurology : the official journal of the European Federation of Neurological Societies 2010 Jul;17 Suppl 1:88-96.
Jankovic J Clinical efficacy and tolerability of Xeomin in the treatment of blepharospasm. European Journal of Neurology : the official journal of the European Federation of Neurological Societies 2009 Dec;16 Suppl 2:14-8.
For additional information regarding Xeomin or cervical dystonias or blephorspasm, please visit the Merz web page.
Xeomin Drug Information
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