Drug Trials Snapshots: EBGLYSS
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 IMDELLTRA 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).
EBGLYSS (lebrikizumab-lbkz)
EHB-glihs
Eli Lilly and Company
Approval date: September 13, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
EBGLYSS is an interleukin-13 antagonist indicated for the treatment of adult and pediatric patients 12 years of age and older who weigh at least 40 kg with moderate to severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
How is this drug used?
EBGLYSS is an injection that is taken at an initial dose of 500 mg (two 250 mg injections) on Day 1 and Day 14 (two weeks later), followed by 250 mg every two weeks until Week 16 or later, when adequate clinical response is achieved.
Who participated in the clinical trials?
The FDA approved EBGLYSS based on evidence from three clinical trials (J2T-DM-KGAB, J2T-DM-KGAC, and J2T-DM-KGAD) of 1,062 patients 12 years of age and older with moderate to severe AD. The trials were conducted at 223 of sites in 16 countries including Australia, Bulgaria, Canada, Estonia, France, Germany, Latvia, Lithuania, Mexico, Poland, Singapore, South Korea, Spain, Taiwan, Ukraine, and the United States. The trials enrolled 508 subjects in the United States and 554 subjects outside the United States.
The number of patients representing efficacy findings may differ from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.
How were the trials designed?
EBGLYSS was evaluated in three clinical trials of 1,062 patients 12 years of age and older with moderate to severe AD whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
The three trials were randomized, double-blind, placebo-controlled, and parallel group studies. Two trials were designed to evaluate the efficacy and safety of EBGLYSS as a monotherapy and one trial was designed to evaluate the safety and efficacy of EBGLYSS when used in combination with topical corticosteroid (TCS) treatment.
The benefit of EBGLYSS was assessed after 16 weeks of treatment using Investigator’s Global Assessment (IGA) scale that measures overall severity of disease on a scale from 0 (clear) to 4 (severe).
How were the trials designed?
The efficacy of EBGLYSS was evaluated in three randomized, double-blind, placebo-controlled, and parallel group trials. Studies KGAB and KGAC were designed to evaluate the efficacy and safety of EBGLYSS as a monotherapy for moderate to severe AD, utilizing a 16-week placebo-controlled period followed by a 36-week maintenance treatment period. Study KGAD was a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the safety and efficacy of EBGLYSS when used in combination with TCS treatment, compared with placebo in combination with TCS for moderate to severe AD.
The primary endpoint for the three studies is percentage of participants with the IGA score of 0 (clear) or 1 (almost clear) and a reduction of ≥2 points from baseline to Week 16.
In all three trials, subjects in the EBGLYSS group received subcutaneous injections of EBGLYSS 500 mg at Week 0 and at Week 2, followed by 250 mg every other week through Week 16.
To evaluate the maintenance and durability of response in the monotherapy trials (KGAB and KGAC), subjects originally randomized to EBGLYSS who achieved an IGA score of 0 or 1, or at least a 75% reduction in the Eczema Area and Severity Index (EASI) from baseline at Week 16 and did not require rescue therapy were re-randomized to an additional 36 weeks of either a maintenance dose of EBGLYSS 250 mg every two weeks, EBGLYSS 250 mg every four weeks, or placebo.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of EBGLYSS.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the combined clinical trials used to evaluate the efficacy of EBGLYSS.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the combined clinical trials used to evaluate the efficacy of EBGLYSS.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of EBGLYSS.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population in Studies KGAB, KGAC, and KGAD
|
Demographic |
KGAB |
KGAC |
KGAD |
||||||
|
Placebo N=141 |
EBGLYSS |
Total |
Placebo |
EBGLYSS |
Total |
Placebo + TCS |
EBGLYSS + TCS |
Total |
|
|
Age group, years, n (%) |
|
|
|
|
|
|
|
|
|
|
Adolescents 12 to <18 |
18 (12.8) |
37 (13.1) |
55 (13.0) |
17 (11.6) |
30 (10.7) |
47 (11.0) |
14 (21.2) |
32 (22.1) |
46 (21.8) |
|
Adults ≥18 to <65 |
113 (80.1) |
225 (79.5) |
338 (79.7) |
119 (81.5) |
228 (81.1) |
347 (81.3) |
47 (71.2) |
98 (67.6) |
145 (68.7) |
|
Adults ≥65 |
10 (7.1) |
21 (7.4) |
31 (7.3) |
10 (6.8) |
23 (8.2) |
33 (7.7) |
5 (7.6) |
15 (10.3) |
20 (9.5) |
|
Race, n (%) |
|
|
|
|
|
|
|
|
|
|
American Indian or Alaska Native |
0 |
7 (2.5) |
7 (1.7) |
2 (1.4) |
3 (1.1) |
5 (1.2) |
2 (3.0) |
5 (3.4) |
7 (3.3) |
|
Asian |
31 (22.0) |
39 (13.8) |
70 (16.5) |
44 (30.1) |
78 (27.8) |
122 (28.6) |
13 (19.7) |
18 (12.4) |
31 (14.7) |
|
Black or African American |
16 (11.3) |
33 (11.7) |
49 (11.6) |
10 (6.8) |
25 (8.9) |
35 (8.2) |
9 (13.6) |
19 (13.1) |
28 (13.3) |
|
Native Hawaiian or other Pacific Islander |
0 |
2 (<1) |
2 (<1) |
1 (<1) |
2 (<1) |
3 (<1) |
0 |
3 (2.1) |
3 (1.4) |
|
White |
93 (66.0) |
196 (69.3) |
289 (68.2) |
85 (58.2) |
168 (59.8) |
253 (59.3) |
40 (60.6) |
900 (62.1) |
130 (61.6) |
|
Multiple |
1 (<1) |
4 (1.4) |
5 (1.2) |
3 (2.1) |
4 (1.4) |
7 (1.6) |
1 (1.5) |
8 (5.5) |
9 (4.3) |
|
Not reported |
0 |
1 (<1) |
1 (<1) |
0 |
0 |
0 |
0 |
0 |
0 |
|
Other |
0 |
1 (<1) |
1 (<1) |
1 (<1) |
1 (<1) |
2 (<1) |
1 (1.5) |
2 (1.4) |
3 (1.4) |
|
Sex, n (%) |
|
|
|
|
|
|
|
|
|
|
Female |
73 (51.8) |
141 (49.8) |
214 (50.5) |
75 (51.4) |
136 (48.4) |
211 (49.4) |
33 (50.0) |
70 (48.3) |
103 (48.8) |
|
Male |
68 (48.2) |
142 (50.2) |
210 (49.5) |
71 (48.6) |
145 (51.6) |
216 (50.6) |
33 (50.0) |
75 (51.7) |
108 (51.2) |
|
Ethnicity, n (%) |
|
|
|
|
|
|
|
|
|
|
Hispanic or Latino |
16 (11.3) |
25 (8.8) |
41 (9.7) |
17 (11.6) |
33 (11.7) |
50 (11.7) |
15 (22.7) |
30 (20.7) |
45 (21.3) |
|
Not Hispanic or Latino |
125 (88.7) |
252 (89.0) |
377 (88.9) |
127 (87.0) |
244 (86.8) |
371 (86.9) |
51 (77.3) |
112 (77.2) |
163 (77.3) |
|
Not reported |
0 |
4 (1.4) |
4 (<1) |
2 (1.4) |
4 (1.4) |
6 (1.4) |
0 |
2 (1.4) |
2 (<1) |
|
Unknown |
2 (<1) |
2 (<1) |
0 |
0 |
0 |
0 |
1 (<1) |
1 (<1) |
|
Source: Adapted from FDA Review
Abbreviations: TCS, topical corticosteroids
What are the benefits of this drug?
In the three trials, a greater percentage of participants achieved IGA 0 or 1, with a 2-point or more reduction at Week 16 in the EBGLYSS-treated group compared with the placebo-treated group.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes efficacy results for primary endpoint of the monotherapy trials (KGAB and KGAC). The results in the concomitant therapy trial (KGAD) at Week 16, where subjects received EBGLYSS + TCS or placebo + TCS were consistent with the results in the monotherapy trials.
Table 2. Percentage of Participants With an IGA Score of 0 or 1 and a ≥2-Point Reduction From Baseline at Week 16, Efficacy Population, Studies KGAB and KGAC
|
Parameter |
KGAB |
KGAC |
||
|
Placebo |
EBGLYSS |
Placebo |
EBGLYSS |
|
|
Response, n (%)1 |
18 (12.7) |
122 (43.1) |
16 (10.8) |
93 (33.2) |
|
Difference (95% CI)2 |
29.7 (21.6, 37.8) |
21.9 (14.2, 29.6) |
||
Source: Adapted from FDA Review
1 Unadjusted response rate.
2 The common risk difference is the difference in proportions adjusted by geographic region (United States versus European Union versus rest of world), age (adolescent patients 12 to >e;18 versus adults ≥18 years) and disease severity (IGA 3 versus 4) where the confidence intervals are calculated using Mantel-Haenszel-Sato method.
Abbreviations: CI, confidence interval; IGA, Investigator Global Assessment
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: EBGLYSS worked similarly in females and males.
- Race: EBGLYSS worked similarly in White, Asian, and Black or African American participants. The number of participants of other races was limited; therefore, differences in response among other races could not be determined.
- Age: EBGLYSS worked similarly in participants 12 to 17 years of age and 18 years of age and older.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 summarizes efficacy results for primary endpoint by subgroup in Studies KGAB and KGAC.
Table 3. IGA (0,1) With 2-Point Improvement Response Rates at Week 16 by Subgroup, Efficacy Population, Studies KGAB and KGAC
|
Subgroup |
Placebo N=287 n/Ns (%) |
EBGLYSS N=564 n/Ns (%) |
Difference (95% CI)1 |
|
Sex |
|
|
|
|
Female |
18/148 (12.5) |
125/277 (45.3) |
32.8 (24.6, 41.0) |
|
Male |
15/139 (11.0) |
90/287 (31.2) |
20.3 (12.6, 27.9) |
|
Race |
|
|
|
|
American Indian or Alaska Native |
0/2 (0.0) |
4/10 (40.0) |
40.0 (9.6, 70.4) |
|
Asian |
3/75 (4.1) |
29/117 (25.1) |
21.1 (12.0, 30.2) |
|
Black or African American |
3/26 (13.2) |
19/58 (33.2) |
19.9 (1.2, 38.7) |
|
Native Hawaiian or other Pacific Islander |
1/1 (100.0) |
2/4 (52.0) |
-48.0 (NA, NA) |
|
White |
25/178 (14.1) |
158/364 (43.3) |
29.2 (21.7, 36.7) |
|
Multiple |
1/4 (29.3) |
1/8 (12.5) |
-14.5 (-68.3, 39.3) |
|
Other |
0/1 (0.0) |
1/2 (50.0) |
50.0 (NA, NA) |
|
Not reported |
- |
1/1 (72.0) |
- |
|
Age, years |
|
|
|
|
Adolescents 12 to <18 |
5/35 (14.3) |
31/67 (46.6) |
32.3 (15.6, 49.0) |
|
Adults ≥18 to <65 |
28/232 (11.9) |
169/453 (37.3) |
25.3 (19.0, 31.7) |
|
Adults ≥65 |
1/20 (5.2) |
15/44 (34.2) |
29.0 (11.4, 46.6) |
|
Ethnicity |
|
|
|
|
Hispanic or Latino |
6/33 (19.2) |
23/58 (39.7) |
20.5 (1.2, 39.8) |
|
Not Hispanic or Latino |
27/252 (10.9) |
188/496 (38.0) |
27.1 (21.2, 33.0) |
|
Not reported |
0/2 (0.0) |
4/8 (46.5) |
46.5 (NA, NA) |
|
Missing |
- |
0/2 (0.0) |
- |
Source: Adapted from FDA Review
Note: Some values are not available, denoted by NA, due to the small number of responders in the specified category.
1 Unadjusted response rate and confidence interval. Treatment group differences are evaluated within each subgroup using the chi-square test.
Abbreviations: CI, confidence interval; IGA (0,1), Investigator Global Assessment score 0 (clear) or 1 (almost clear); n, number of responders in the specified category; N, number of patients in the analysis population; Ns, number of patients in the specified subgroup
What are the possible side effects?
The most frequent adverse reactions were injection site reactions (pain, redness, discomfort, dermatitis, itching, swelling, and rash), conjunctivitis (pink eye), and herpes zoster (shingles). Hypersensitivity reactions including hives and angioedema were also reported.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes the most common adverse reactions occurring greater than placebo and <1% during the EBGLYSS trials.
Table 4. Adverse Reactions Occurring in ≥1% of the EBGLYSS Monotherapy Group or the EBGLYSS + TCS Group in the Atopic Dermatitis Trials Through Week 16
|
Adverse Reactions |
EBGLYSS Monotherapya |
EBGLYSS + TCSb |
|||
|
EBGLYSS 250 mg Q2Wc N=638 n (%) |
Placebo N=338 n (%) |
EBLYSS 250 mg Q2Wc + TCS N=145 n (%) |
Placebo + TCS N=66 n (%) |
||
|
Conjunctivitisd |
61 (10) |
10 (3) |
7 (5) |
0 |
|
|
Injection site reactionse |
16 (3) |
4 (1) |
4 (3) |
1 (2) |
|
|
Herpes zoster |
3 (<1) |
0 |
2 (1) |
0 |
|
Source: EBGLYSS Prescribing Information
a Integrated analysis of KGAB, KGAC, and the phase 2 dose finding trial (KGAF)
b Analysis of TCS concomitant therapy trial KGAD
c EBGLYSS 500 mg at Week 0 and Week 2, followed by 250 mg every two weeks
d Conjunctivitis cluster includes conjunctivitis, conjunctivitis allergic, and conjunctivitis bacterial
e Injection site reactions cluster includes injection site-related: pain, erythema, reaction, discomfort, dermatitis, pruritus, swelling, and rash
Abbreviations: Q2W, every two weeks; TCS, topical corticosteroid
/accordions]
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of subjects of races other than White was small; therefore, differences among races in side effects from EBGLYSS could not be determined.
- Age: Observed side effects from EBGLYSS were seen more often in adults (18 to <65 years) than in adolescents (12 to <18 years). Because of limited data, this difference may be due to chance. The number of subjects 65 years of age and older was small, therefore differences in this age group and younger subjects could not be determined. .
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Side Effects by Sex Occurring in at Least 1% of Subjects From the Placebo-Controlled Period
| Preferred Terms |
Placebo |
EBGLYSS |
||
|
Female N=212 n (%) |
Male N=205 n (%) |
Female N=412 n (%) |
Male N=393 n (%) |
|
|
Subjects with at least one event |
111 (52) |
110 (54) |
202 (49) |
192 (49) |
|
Conjunctivitis |
2 (1) |
5 (2) |
22 (5) |
29 (7) |
|
Dermatitis atopic |
34 (16) |
40 (20) |
23 (6) |
24 (6) |
|
Nasopharyngitis |
7 (3) |
7 (3) |
15 (4) |
20 (5) |
|
Headache |
10 (5) |
4 (2) |
18 (4) |
17 (4) |
|
Conjunctivitis allergic |
2 (1) |
1 (<1) |
5 (1) |
9 (2) |
|
Dry eye |
2 (1) |
2 (1) |
3 (<1) |
8 (2) |
|
Oral herpes |
6 (3) |
3 (1) |
7 (2) |
8 (2) |
|
Hypertension |
2 (1) |
2 (1) |
5 (1) |
4 (1) |
|
Rhinitis allergic |
0 |
1 (<1) |
4 (1) |
4 (1) |
|
COVID-19 |
5 (2) |
0 |
8 (2) |
1 (<1) |
Source: Adapted from FDA Review
Table 6. Side Effects by Age Group (Years) Occurring in at Least 1% of Subjects From the Placebo-Controlled Period
| Preferred Term |
Placebo |
EBGLYSS |
||||||
|
12 to <18 N=52 n (%) |
≥18 to <65 N=331 n (%) |
≥65 to <75 N=28 n (%) |
≥75 N=6 n (%) |
12 to <18 N=105 n (%) |
≥18 to <65 N=632 n (%) |
≥65 to <75 N=53 n (%) |
≥75 N=15 n (%) |
|
|
Subjects with at least one event |
29 (56) |
176 (53) |
11 (39) |
5 (83) |
38 (36) |
328 (52) |
19 (36) |
9 (60) |
|
Conjunctivitis |
1 (2) |
5 (2) |
0 |
1 (17) |
4 (4) |
47 (7) |
0 |
0 |
|
Dermatitis atopic |
3 (6) |
58 (18) |
2 (7) |
3 (50) |
5 (5) |
36 (6) |
3 (6) |
3 (20) |
|
Headache |
2 (4) |
10 (3) |
0 |
1 (17) |
3 (3) |
30 (5) |
2 (4) |
0 |
|
Nasopharyngitis |
1 (2) |
12 (4) |
0 |
0 |
5 (5) |
29 (5) |
1 (2) |
0 |
|
Oral herpes |
1 (2) |
6 (2) |
1 (4) |
1 (17) |
1 (1) |
14 (2) |
0 |
0 |
|
Conjunctivitis allergic |
1 (2) |
2 (<1) |
0 |
0 |
2 (2) |
12 (2) |
0 |
0 |
|
COVID-19 |
1 (2) |
4 (1) |
0 |
0 |
0 |
8 (1) |
1 (2) |
0 |
|
Dry eye |
0 |
4 (1) |
0 |
0 |
3 (3) |
8 (1) |
0 |
0 |
|
Hypertension |
0 |
3 (1) |
1 (4) |
0 |
0 |
7 (1) |
2 (4) |
0 |
|
Pruritus |
2 (4) |
5 (2) |
0 |
0 |
2 (2) |
6 (<1) |
1 (2) |
0 |
|
Rhinitis allergic |
0 |
1 (<1) |
0 |
0 |
2 (2) |
6 (<1) |
0 |
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.