Drug Trials Snapshots: LETYBO
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the LETYBO Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
LETYBO (letibotulinumtoxinA)
(le tye' boe)
Hugel, Inc.
Approval date: February 29, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
LETYBO is a drug used in adults to temporarily improve the appearance of moderate to severe glabellar lines (wrinkles between the eyebrows).
How is this drug used?
LETYBO is given by a healthcare provider directly into the muscle through a needle (known as an intramuscular injection). It is injected into five different sites of the muscles of the frown lines. LETYBO should not be given more frequently than every three months.
Who participated in the clinical trials?
The FDA approved LETYBO based on evidence from three clinical trials (BLESS I [NCT02677298], BLESS II [NCT02677805], and BLESS III [NCT03985982]) of 1,271 patients with moderate to severe wrinkles between the eyebrows for efficacy and safety assessment. These trials were conducted at 31 sites in the United States and European Union.
How were the trials designed?
The benefit and side effects of LETYBO were primarily evaluated in three clinical trials.
All three trials enrolled patients 18 to 75 years old with moderate to severe glabellar lines (wrinkles between the eyebrows). Patients received a single intramuscular injection of LETYBO or placebo at five sites within the muscles between the eyebrows.
The benefit of LETYBO was assessed by determining the proportion of patients achieving a score of 0 or 1 (none or mild) and at least a 2-grade improvement of wrinkles between the eyebrows at maximum frown from baseline to Week 4. Improvement of wrinkles between the eyebrows at maximum frown was assessed independently by both the investigator and the patient using the Glabellar Line Scale (GLS). The GLS is a 4-point grading scale (0 = none, 1 = mild, 2 = moderate, 3 = severe).
How were the trials designed?
The efficacy and safety of LETYBO were primarily evaluated in three randomized, double-blind, placebo-controlled trials.
All three trials enrolled patients ranging in age from 18 to 75 years old with moderate to severe glabellar facial lines at maximum frown. Patients were randomized to receive a single treatment with LETYBO or placebo intramuscularly. Patients received intramuscular injections (0.1 mL/injection site) of LETYBO or placebo at five sites, one in the procerus muscle and two in each corrugator supercilii muscle.
The primary efficacy endpoint was the proportion of patients achieving a score of 0 or 1 (none or mild) and at least a 2-grade improvement from baseline at maximum frown at Week 4. Improvement of glabellar line severity at maximum frown was assessed independently by both the investigator and the patient using the GLS (0 = none, 1 = mild, 2 = moderate, 3 = severe).
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female participants were enrolled in the combined clinical trials used to evaluate the efficacy of LETYBO.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of participants by race enrolled in the combined clinical trials used to evaluate the efficacy of LETYBO.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of participants by age enrolled in the combined clinical trials used to evaluate the efficacy of LETYBO.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of participants by ethnicity enrolled in the combined clinical trials used to evaluate the efficacy of LETYBO.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics of Efficacy Trials by Age, Sex, Race, Ethnicity, and Region
| Demographic | BLESS I | BLESS II | BLESS III | |||
|---|---|---|---|---|---|---|
| LETYBO N=528 |
Placebo N=175 |
LETYBO N=160 |
Placebo N=53 |
LETYBO N=266 |
Placebo N=89 |
|
| Age, years | ||||||
| Mean | 49.3 | 48.7 | 52 | 52.4 | 52.2 | 49.4 |
| Median | 49 | 49 | 52.5 | 51 | 53 | 52 |
| Range (min, max) | 19, 75 | 21, 74 | 27, 75 | 29, 73 | 21, 75 | 22, 75 |
| Age group, years, n (%) | ||||||
| 18 to 64 | 462 (87.5) | 157 (89.7) | 141 (88.1) | 45 (84.9) | 233 (87.6) | 81 (91.0) |
| 65 to 75 | 66 (12.5) | 18 (10.3) | 19 (11.9) | 8 (15.1) | 33 (12.4) | 8 (9.0) |
| Sex, n (%) | ||||||
| Female | 483 (91.5) | 155 (88.6) | 150 (93.8) | 45 (84.9) | 248 (93.2) | 80 (89.9) |
| Male | 45 (8.5) | 20 (11.4) | 10 (6.3) | 8 (15.1) | 18 (6.8) | 9 (10.1) |
| Race, n (%) | ||||||
| White | 482 (91.3) | 153 (87.4) | 153 (95.6) | 50 (94.3) | 236 (88.7) | 79 (88.8) |
| Black or African American | 33 (6.3) | 18 (10.3) | 3 (1.9) | 1 (1.9) | 25 (9.4) | 7 (7.9) |
| Asian | 7 (1.3) | 3 (1.7) | 2 (1.3) | 1 (1.9) | 4 (1.5) | 1 (1.1) |
| American Indian or Alaska Native | 2 (0.4) | 0 | 1 (0.6) | 0 | 0 | 0 |
| Native Hawaiian or Pacific Islander | 0 | 0 | 0 | 1 (1.9) | 0 | 0 |
| Other | 4 (0.8) | 1 (0.6) | 1 (0.6) | 0 | 1 (0.4) | 2 (2.2) |
| Ethnicity, n (%) | ||||||
| Not Hispanic or Latino | 497 (94.1) | 166 (94.9) | 126 (78.8) | 45 (84.9) | 200 (75.2) | 67 (75.3) |
| Hispanic or Latino | 25 (4.7) | 8 (4.6) | 33 (20.6) | 7 (13.2) | 66 (24.8) | 22 (24.7) |
| Missing | 6 (1.1) | 1 (0.6) | 1 (0.6) | 1 (1.9) | 0 | 0 |
| Region, n (%) | ||||||
| United States | 268 (50.8) | 95 (54.3) | 160 (100) | 53 (100) | 225 (84.6) | 79 (88.8) |
| European Union | 260 (49.2) | 80 (45.7) | 0 | 0 | 41 (15.4) | 10 (11.2) |
Source: Adapted from FDA Review
What are the benefits of this drug?
In all three trials, patients with moderate to severe wrinkles between the eyebrows had improvement of frown lines four weeks after treatment with LETYBO. In Trial BLESS I, 47% of patients treated with LETYBO had temporary improvement of wrinkles between the eyebrows compared to 0% of patients in the group that received placebo. In Trial BLESS II, 49% of patients treated with LETYBO had temporary improvement of wrinkles between the eyebrows compared to 2% of patients in the group that received placebo. In Trial BLESS III, 65% of patients treated with LETYBO had temporary improvement of wrinkles between the eyebrows compared to 0% of patients in the group that received placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes efficacy results for the evaluated patients in the clinical trials. The primary efficacy endpoint was the proportion of patients who achieved treatment success, defined as a score of 0 or 1 (none or mild) and at least a 2-grade improvement from baseline to Week 4 at maximum frown, as assessed independently by both the investigator and the patient using the GLS. The GLS is a 4-point grading scale (0 = none, 1 = mild, 2 = moderate, 3 = severe).
Table 2. Percentage of Subjects With Moderate to Severe Glabellar Lines Achieving a Score of None or Mild and At Least a 2-Grade Improvement From Baseline on the Investigator and Subject Assessment of Glabellar Line Severity at Maximum Frown at Week 4
| Endpoint | BLESS I | BLESS II | BLESS III | |||
|---|---|---|---|---|---|---|
| LETYBO N=528 n (%) |
Placebo N=175 n (%) |
LETYBO N=160 n (%) |
Placebo N=53 n (%) |
LETYBO N=266 n (%) |
Placebo N=89 n (%) |
|
| Treatment success | ||||||
| Multi-component assessment | 246 (47) | 0 (0) | 78 (49) | 1 (2) | 172 (65) | 0 (0) |
| Treatment difference (95% CI) | 47 (43, 51) | 45 (36, 54) | 65 (59, 71) | |||
| Individual components | ||||||
| Investigator assessment | 348 (66) | 1 (1) | 120 (75) | 1 (2) | 209 (79) | 1 (1) |
| Subject assessment | 290 (55) | 0 (0) | 83 (52) | 1 (2) | 183 (69) | 0 (0) |
Source: LETYBO Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The majority of patients were female. The number of male patients was limited; therefore, differences in how well LETYBO worked in male patients compared to female patients could not be determined.
- Race: The majority of patients were White. The number of patients in other races were limited; therefore, differences in how well LETYBO worked among races could not be determined.
- Age: The majority of patients were younger than 65 years of age; therefore, differences in how well LETYBO worked among younger versus older age groups could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 summarizes efficacy results by subgroup based on the proportion of patients achieving a score of 0 or 1 (none or mild) and at least a 2-grade improvement from baseline at maximum frown at Week 4.
Table 3. Primary Efficacy Results by Subgroup
| Subgroup | BLESS I | BLESS II | BLESS III | |||
|---|---|---|---|---|---|---|
| LETYBO N=528 n/Ns (%) |
Placebo N=175 n/Ns (%) |
LETYBO N=160 n/Ns (%) |
Placebo N=53 n/Ns (%) |
LETYBO N=266 n/Ns (%) |
Placebo N=89 n/Ns (%) |
|
| Age group, years | ||||||
| 18 to 64 | 222/462 (48.1) | 0/157 (0) | 73/141 (51.8) | 1/45 (2.2) | 155/233 (66.5) | 0/81 (0) |
| 65 to 75 | 24/66 (36.4) | 0/18 (0) | 5/19 (26.3) | 0/8 (0) | 17/33 (51.5) | 0/8 (0) |
| Sex | ||||||
| Female | 230/483 (47.6) | 0/155 (0) | 77/150 (51.3) | 1/45 (2.2) | 166/248 (66.9) | 0/80 (0) |
| Male | 16/45 (35.6) | 0/20 (0) | 1/10 (10.0) | 0/8 (0) | 6/18 (33.3) | 0/9 (0) |
| Race | ||||||
| White | 216/482 (44.8) | 0/153 (0) | 75/153 (49.0) | 1/50 (2.0) | 157/236 (66.5) | 0/79 (0) |
| Black or African American | 22/33 (66.7) | 0/18 (0) | 2/3 (66.7) | 0/1 (0) | 12/25 (48.0) | 0/7 (0) |
| Asian | 5/7 (71.4) | 0/3 (0) | 0/2 (0) | 0/1 (0) | 2/4 (50.0) | 0/1 (0) |
| American Indian or Alaska Native | 1/2 (50.0) | NA | 1/1 (100) | NA | NA | NA |
| Native Hawaiian or Pacific Islander | NA | NA | NA | 0/1 (0) | NA | NA |
| Other | 2/4 (50.0) | 0/1 (0) | 0/1 (0) | NA | 1/1 (100) | 0/2 (0) |
| Ethnicity | ||||||
| Not Hispanic or Latino | 233/497 (46.9) | 0/166 (0) | 60/126 (47.6) | 0/45 (0) | 121/200 (60.5) | 0/67 (0) |
| Hispanic or Latino | 10/25 (40.0) | 0/8 (0) | 18/33 (54.5) | 1/7 (14.3) | 51/66 (77.3) | 0/22 (0) |
| Missing | 3/6 (50.0) | 0/1 (0) | 0/1 (0) | 0/1 (0) | NA | NA |
| Region | ||||||
| United States | 146/268 (54.5) | 0/95 (0) | 78/160 (48.8) | 1/53 (1.9) | 153/225 (68.0) | 0/79 (0) |
| European Union | 100/260 (38.5) | 0/80 (0) | NA | NA | 19/41 (46.3) | 0/10 (0) |
| Previous use of botulinum toxin | ||||||
| No | 160/345 (46.4) | 0/116 (0) | 49/105 (46.7) | 1/42 (2.4) | 106/169 (62.7) | 0/53 (0) |
| Yes | 86/183 (47.0) | 0/59 (0) | 29/55 (52.7) | 0/11 (0) | 66/97 (68.0) | 0/36 (0) |
Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients meeting criteria; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
What are the possible side effects?
Botulinum toxin products may spread from the area of injection to other areas and cause serious life-threatening side effects including swallowing and difficulty breathing that could lead to death. Spread of botulinum toxin products to other areas can also cause loss of strength and muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly, and loss of bladder control.
Other serious side effects of botulinum toxin products include severe allergic reactions and heart attack.
The most common side effects of LETYBO are headache, drooping of eyelid and brow, and twitching of eyelid.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes adverse reactions in patients with moderate to severe glabellar lines in the clinical trials.
Table 4. Adverse Reactions Reported in More Than One Subject in the LETYBO Group Compared to the Placebo Group in BLESS I, II, and III
| Adverse Reaction | LETYBO N=911 n (%) |
Placebo N=310 n (%) |
|---|---|---|
| Headachea | 17 (2) | 2 (1) |
| Brow ptosisb | 3 (<1) | 0 |
| Eyelid ptosis | 3 (<1) | 0 |
| Blepharospasm | 2 (<1) | 0 |
Source: LETYBO Prescribing Information
a Includes headache, head discomfort, migraine, and procedural headache
b Includes brow ptosis and brow heaviness
Were there any differences in side effects among sex, race and age?
- Sex: The majority of patients were female. The number of male patients was limited; therefore, differences in the occurrence of side effects among male patients compared to female patients could not be determined.
- Race: The majority of patients were White. The number of patients in other races were limited; therefore, differences in in the occurrence of side effects among races could not be determined.
- Age: The majority of patients were younger than 65 years of age; therefore, differences in the occurrence of side effects among younger and older age groups could not be determined.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Subgroup Analysis of Headache
| Demographic Characteristic | LETYBO N=911 n (%) |
Placebo N=310 n (%) |
|---|---|---|
| Age group, years | ||
| 18 to 64 | 16 (2) | 2 (1) |
| 65 to 75 | 1 (<1) | 0 |
| Sex | ||
| Female | 16 (2) | 2 (1) |
| Male | 1 (<1) | 0 |
| Race | ||
| White | 17 (2) | 2 (1) |
| Black or African American | 0 | 0 |
| Asian | 0 | 0 |
| American Indian or Alaska Native | 0 | 0 |
| Native Hawaiian or Pacific Islander | 0 | 0 |
| Other | 0 | 0 |
| Ethnicity | ||
| Not Hispanic or Latino | 16 (2) | 2 (1) |
| Hispanic or Latino | 1 (<1) | 0 |
Source: Adapted from FDA Review
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.