Regulatory Decision Summary for Botox Cosmetic

The Sponsor has submitted a Supplemental New Drug Submission (SNDS) Level 1 Change for Botox Cosmetic (onabotulinumtoxinA) for the addition of a new indication.

After evaluation of the submitted data package, Health Canada authorized Botox Cosmetic for the following indication at the requested dose is 26 to 36 units across 18 to 28 sites of injection along the jawline (inferior to the lower mandibular border) and vertical neck bands.

Lower Facial Muscle Prominence

• for the improvement in the appearance of platysma prominence in adults.

The safety and effectiveness of dosing with Botox Cosmetic more frequently than every 3 months have not been evaluated.

Authorization was based on two pivotal, Phase 3, multicentre, randomized, double-blind, placebo-controlled clinical studies and three supportive studies. The supportive studies included a Phase 3, open-label extension study to evaluate the safety of up to 3 retreatments with Botox, a Phase 2 dose-ranging study, and a non-interventional scale validation study.

Two Phase 3 studies evaluated Botox Cosmetic (N = 408 Botox Cosmetic and N = 426 placebo) for the improvement in the appearance of moderate to severe platysma prominence. Based on baseline severity, subjects were randomized to receive a single treatment of Botox Cosmetic or placebo. The primary efficacy measure was the assessment of platysma prominence severity at maximum contraction using the 5-grade Clinician Allergan Platysma Prominence Scale (C-APPS) by the investigators, and the 5-grade Participant Allergan Platysma Prominence Scale (P-APPS) by the subjects. For both scales, the 5 grades are 1 = Minimal, 2 = Mild, 3 = Moderate, 4 = Severe, 5 = Extreme. C-APPS and P-APPS assessments were performed independently. The primary efficacy timepoint was Day 14 after the first treatment.

The proportion of responders was greater in the Botox Cosmetic group compared to placebo at Day 14. Both pivotal Phase 3 clinical trials met the primary efficacy endpoint.

In pivotal studies, 30 subjects were 65 years of age or older. The responder rates appeared to be higher for subjects younger than age 65 than for subjects 65 years or older. Studies specifically designed to determine the dose in geriatric (≥ 65 years of age) patients have not been performed.

Eligible subjects who completed the lead-in study had the option to participate in an open-label extension study with up to 3 additional Botox Cosmetic treatments for platysma prominence. The main purpose of the open-label extension study was to assess the safety of up to 3 retreatments with Botox Cosmetic, this study was not powered to assess efficacy, as such only trends in efficacy may be observed. In these subjects, similar trends in efficacy were observed with each subsequent Botox Cosmetic treatment for platysma prominence severity.

There were no adverse reactions reported by ≥ 1% of Botox Cosmetic-treated subjects and more frequent than in placebo-treated subjects. Adverse reactions that occurred at < 1% among 350 Botox Cosmetic-treated subjects include mild dysphagia in 3 subjects and mild facial paresis in 2 subjects. No change was observed in the overall safety profile with repeat dosing up to 4 treatments with Botox Cosmetic.

In conclusion, the benefit of Botox Cosmetic for the improvement in the appearance of moderate to severe platysma prominence outweighed the potential safety events as identified in the product monograph. The risks are considered sufficiently mitigated through the thorough disclosures in the product monograph.

An updated Risk Management Plan (RMP) for Botox Cosmetic was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered acceptable.

For further details about Botox Cosmetic, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.