Source: FDA, National Drug Code (US) Revision Year: 2024
LETYBO blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine. When injected intramuscularly at therapeutic doses, LETYBO is internalized into the nerve terminal, translocates into the neuronal cytosol where it cleaves SNAP25, a protein necessary for synaptic membrane docking and subsequent release of acetylcholine which produces a dose dependent decrease of muscle function. Recovery of muscle function is gradual due to degradation of the neurotoxin and formation of axonal sprouts. Muscle reinnervation occurs, leading to a slow reversal of the pharmacological effects of LETYBO.
No formal pharmacodynamic studies have been conducted with LETYBO.
Using currently available analytical technology, it is not possible to detect LETYBO in the peripheral blood following intramuscular injection at the recommended doses.
Animal studies have not been conducted to evaluate the carcinogenic, mutagenic, or impairment of fertility potential of letibotulinumtoxinA-wlbg.
Three randomized, multi-center, double-blind, placebo-controlled trials (BLESS I [NCT02677298], BLESS II [NCT02677805] and BLESS III [NCT03985982]) of identical design were conducted to evaluate LETYBO for use in the temporary improvement of the appearance of moderate to severe glabellar facial lines. These trials enrolled 1,276 subjects, randomized 3 to 1 to a single treatment with LETYBO (n=957) or placebo (n=319). Of the 1,276 enrolled subjects, 1,271 were included in the full analysis set (FAS) evaluable for efficacy with LETYBO (n=954) and placebo (n=317).
The trials enrolled healthy adults (ranging in age from 19 to 75) with glabellar lines of at least moderate severity at maximum frown and excluded subjects who had ptosis, deep dermal scarring or an inability to substantially lessen glabellar lines even by physically spreading the glabellar lines apart. The mean age was 50 years with 152 subjects (12%) ≥65 years of age. Most of the subjects were women (91%) and White (91%). Injection volume was 0.1 mL/injection site, for a dose/injection site in the active treatment groups of 4 Units. Subjects were injected intramuscularly at 5 sites, 1 in the procerus muscle and 2 in each corrugator supercilii muscle, for a total dose in the active treatment groups of 20 Units.
The primary efficacy endpoint was measured at Week 4 and was defined as the proportion of subjects achieving a score of 0 or 1 and an improvement of at least 2 points from baseline at maximum frown, as assessed independently by both the investigator and the subject using the Glabellar Line Scale (GLS). The GLS is a 4- point grading scale (0=none, 1=mild, 2=moderate, 3=severe). The results of these 3 efficacy trials are presented in Table 3.
Table 3: Percentage of Subjects with Moderate to Severe Glabellar Lines Achieving a Score of 0 or 1 and an Improvement of At Least 2 Points from Baseline to Week 4 at Maximum Frown on the Investigator and Subject Assessment of Glabellar Line Severity (Full Analysis Set) in Trials BLESS I, II, and III:
| BLESS I | BLESS II | BLESS III | ||||
|---|---|---|---|---|---|---|
| LETYBO (N = 528) | Placebo (N = 175) | LETYBO (N = 160) | Placebo (N = 53) | LETYBO (N = 266) | Placebo (N = 89) | |
| Treatment Success* | ||||||
| Multi-component Assessment n (%) | 246 (47%) | 0 (0%) | 78 (49%) | 1 (2%) | 172 (65%) | 0 (0%) |
| Treatment Difference and 95% Confidence Interval** | 47% (43%, 51%) | 45% (36%, 54%) | 65% (59%, 71%) | |||
| Individual Components | ||||||
| Investigator Assessment n (%) | 348 (66%) | 1 (1%) | 120 (75%) | 1 (2%) | 209 (79%) | 1 (1%) |
| Subject Assessment n (%) | 290 (55%) | 0 (0%) | 83 (52%) | 1 (2%) | 183 (69%) | 0 (0%) |
* A score of 0 or 1 (none or mild) and an improvement of at least 2 points from baseline at maximum frown concurrently on both the investigator’s and subject’s assessments
** Based on the Mantel-Haenszel method
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
