Regulatory Decision Summary for Letybo

Authorization was primarily based on three pivotal phase III clinical trials (BLESS I, BLESS II and BLESS III) conducted in United States and European countries in subjects with moderate to severe glabellar frown lines.

The three BLESS trials were parallel-group, randomized, double-blind, multi-center, placebo-controlled clinical studies followed by an open-label extension phase with identical study design. Each treatment cycle lasted at least 12 weeks and up to 48 weeks. Subjects were randomized to receive a single intramuscular dose in the glabellar region with either 20 units Letybo or placebo on Day 1 in the first treatment cycle. After the first treatment cycle, all eligible subjects received 20 units Letybo on Day 1 of each of the subsequent treatment cycles in the open-label extension phase.

1,272 subjects were randomized and received a single treatment with Letybo (n = 955) or placebo (n = 317) in double-blind phase. Overall, 1,162 subjects received Letybo treatment in any part of the three studies. For efficacy assessment, composite response was defined as having ≥2-point improvement in Facial Wrinkle Score (FWS) score at maximum frown from baseline and achieving a score of 0 or 1 at a visit of concern following the first injection as assessed independently by both the investigator and the subject.

Superiority of Letybo in improvement of glabellar lines over placebo was consistently demonstrated in the three pivotal BLESS clinical trials in terms of the composite responder rate at Week 4 following the first treatment (the primary efficacy). The difference was 46.5%, 46.9%, and 64.7% in BLESS I, BLESS II and BLESS III, respectively, and clearly clinical meaningful. The composite responder rate in the Letybo group dropped to 12.7%, 4.4%, and 21.1% at Week 12 in BLESS I, BLESS II and BLESS III, respectively.

The observed safety profile for Letybo in treatment of glabellar lines in the BLESS studies appears comparable to the known safety profile of Botulinum toxin A (BoNT/A) products marketed in Canada. In treatment of glabellar lines with the product (20 unit/treatment session), local toxin spread was uncommon. One case of possible distant toxin spread (dysarthria) was reported. All reported adverse event of special interest (AESIs) were not severe and not serious.

In conclusion, the studies in the non-clinical and clinical programmes presented in this submission have demonstrated clinical efficacy of Letybo (20 Units/per treatment session) in treatment of glabellar lines with a safety profile similar to that of BoNT/A products marketed in Canada. Overall, the Letybo has a favorable benefit/risk ratio in treatment of glabellar lines at a single dose of 20 units in a treatment cycle not short than 12 weeks.

The Product Monograph (PM) for Letybo carries the same box warnings as shown in the PM of BoNT/A products marketed in Canada for cosmetic indications.