CLINICAL DATA

EXTENSIVELY TESTED
XEOMIN® is clinically proven to temporarily improve the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.

Using criteria based on combined physician and patient reported response, XEOMIN® was proven to deliver significantly superior efficacy over placebo at Day 30 in two randomized, double-blind, multi-center clinical trials.1-3

The studies enrolled 547 healthy patients (=18 years old) with glabellar lines of at least moderate severity at maximum frown. Three hundred and sixty six subjects were treated with 20 Units of XEOMIN® and 181 subjects were treated with placebo. Subjects were excluded if they had marked ptosis, deep dermal scarring, or an inability to lessen glabellar lines, even by physically spreading them apart. XEOMIN® treated subjects ranged from 24 to 74 years of age with a mean age of 46.

Patients were classified as responders only if they had a 2-grade improvement on a 4-point scale compared to baseline, as assessed by both the investigator and subject. Using these criteria, the percentage of subjects with treatment success was greater on the XEOMIN® arm than the placebo arm at Day 30 in both studies.1-3

Table 1. Treatment Success at Day 301 (at least 2 grades of improvement from baseline at maximum frown)

STUDY 1 STUDY 2
XEOMIN® (N=184) Placebo (N=92) XEOMIN® (N=182) Placebo (N=89)
Composite treatment success* 111(60%) 0(0%) 87(48%) 0(0%)
Investigator assessment 141(77%) 0(0%) 129(71%) 0(0%)
Subject assessment 120(65%) 0(0%) 101(55%) 1(1%)

*Success on both the Investigator and Subject Assessments

In addition, the percentage of patients achieving investigator-rated scores of 0 (none) or 1 (mild) for glabellar lines at Day 30, at maximum frown, were 79.9% and 76.4% in the incobotulinumtoxinA groups in each study respectively, compared with 0.0% for placebo in both studies (p<0.0001 for both comparisons).1-3

HEAD TO HEAD STUDY
Independent review panel, treating physicians and treated patients reported results for XEOMIN®(incobotulinumtoxinA) and BOTOX® (onabotulinumtoxinA) during the four months post-treatment.

Designed as a prospective, multicenter, randomized, double blinded, parallel trial, XEOMIN® and BOTOX® subjects were randomized 1:1. The study enrolled 250 healthy female patients (=18 years old) with glabellar lines of at least moderate severity at maximum frown. 122 subjects were treated with 20 Units of XEOMIN® and 128 subjects were treated with 20 Units of BOTOX® in a single treatment cycle. Both groups of treated subjects had a median age of 41.

Patients were classified as responders only if they had a = 1 point improvement from the baseline on the Facial Wrinkle Scale (FWS) at maximum frown as assessed by the independent review panel using subject photographs at one month post treatment. Investigator and subject ratings were also collected at 1, 2, 3 and 4 months using this criteria.

STUDY SAFETY 11.5% of subjects in the XEOMIN® group and 14.1% of subjects in the BOTOX® group reported at least one adverse event during the study. Two serious adverse events were reported, one in each treatment group. Both adverse events were unrelated to study drug. The most common adverse events for both treatments groups were headache (5.7/3.9%), infection (2.5/3.1%) and facial asymmetry (1.6/2.3%) for XEOMIN® and BOTOX® respectively.

EFFICACIOUS PERFORMANCE4
Treated patients reported similar satisfaction between XEOMIN® and BOTOX® at 1,2,3 and 4 months. Independent review panel, treating physicians and treated patients reported similar efficacy profiles for XEOMIN® and BOTOX®.

Patients were classified as responders only if they had a = 1 point improvement from the baseline on the FWS at maximum frown as assessed by the independent review panel using subject photographs at one month post treatment. Investigator and subject ratings were also collected at 1, 2, 3 and 4 months using this criteria.

SUBJECT REPORTED ONSET4
  • Subject reported median onset is similar at 3 days
NO DIFFERENCE IN PEAK EFFECT4
  • In the XEOMIN® (incobotulinumtoxinA) group, 93.1% of subjects reported a peak effect within 4 weeks of treatment and 94.9% of the BOTOX® (onabotulinumtoxinA) subjects reported a peak effect within 4 weeks of treatment.
REFERENCES:

1.Xeomin® (incobotulinumtoxinA) Prescribing Information. Raleigh, NC, Merz North America, Inc., 2015. 2.Carruthers A, Carruthers J, Heinz M, et al. Multicentre, randomized phase III study of a single dose of incobotulinumtoxinA, free from complexing proteins, in the treatment of glabellar frown lines. Dermatol Surg. 2013;39(4):551-8. 3.Hanke CW, Narins RS, Brandt F, et al. A randomized, placebo-controlled, double-blind phase III trial investigating the efficacy and safety of incobotulinumtoxinA in the treatment of glabellar frown lines using a stringent composite endpoint. Dermatol Surg. 2013;39(6):891-9. 4.Kane M, Gold M, Coleman W, et al. IncobotulinumtoxinA versus onabotulinumtoxinA in the treatment of glabellar facial lines: Results from a multicenter, randomized, double-blinded trial. Dermatol Surg. 2015;41(11):1310-9.


INDICATIONS AND USAGE
XEOMIN® (incobotulinumtoxinA) for injection, for intramuscular use is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines with corrugator and/or procerus muscle activity in adult patients.
IMPORTANT SAFETY INFORMATION
WARNING: DISTANT SPREAD OF TOXIN EFFECT
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.

CONTRAINDICATIONS
  • Hypersensitivity reactions have been reported with botulinum toxin products (anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea). If serious and/or immediate hypersensitivity reactions occur further injection of XEOMIN® should be discontinued and appropriate medical therapy immediately instituted. XEOMIN® is contraindicated in patients with a known hypersensitivity to the active substance botulinum toxin type A, or to any of the excipients (human albumin, sucrose) in the formulation.
  • Use in patients with an infection at the injection site could lead to severe local or disseminated infection. XEOMIN® is contraindicated in the presence of infection at the proposed injection site(s).
WARNINGS AND PRECAUTIONS
  • 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.
  • Treatment with XEOMIN® and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. When distant effects occur, additional respiratory muscles may be involved. Patients may require immediate medical attention should they develop problems with swallowing, speech, or respiratory disorders. Dysphagia may persist for several months, which may require use of a feeding tube. Aspiration may result from severe dysphagia [See BOXED WARNING].
  • Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of XEOMIN®.
  • Glabellar Lines: Do not exceed the recommended dosage and frequency of administration of XEOMIN®. In order to reduce the complication of ptosis the following steps should be taken:
    • avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes;
    • corrugator injections should be placed at least 1 cm above the bony supraorbital ridge.
  • XEOMIN® contains human serum albumin. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and Creutzfeldt-Jakob disease (CJD). No cases of transmission of viral diseases or CJD have ever been reported for albumin.
ADVERSE REACTIONS
Glabellar Lines: The most commonly observed adverse reaction (incidence ≥ 2% of patients and greater than placebo) for XEOMIN® was Headache (5.4%).
DRUG INTERACTIONS
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.
USE IN PREGNANCY
Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. XEOMIN® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
PEDIATRIC USE
The safety and effectiveness of XEOMIN® in patients less than 18 years of age have not been established.