Drug Trials Snapshots: ADBRY

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 ADBRY Prescribing Information for all of 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).

ADBRY (tralokinumab-ldrm)
(ad’ bree)
LEO Pharma A/S
Approval date: December 27, 2021

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

ADBRY is a drug for the treatment of moderate-to-severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

How is this drug used?

ADBRY is a subcutaneous (under skin) injection that is taken every 2 weeks. First dose of 600 mg (four 150-mg injections) is followed by 300 mg (two 150-mg injections) given every two weeks. After 16 weeks, dosing frequency may be decreased to 300 mg (two 150-mg injections) given every 4 weeks for some patients who achieve a response of clear or almost clear. ADBRY can be used with or without topical corticosteroids.

Who participated in the clinical trials?

The FDA approved ADBRY based on evidence from three clinical trials of 1,934 patients with moderate-to-severe atopic dermatitis (AD) not adequately controlled by topical medication(s). The trials were conducted at 284 sites in the United States, Canada, France, Germany, Denmark, Belgium, Poland, Netherlands, Spain, Italy, Great Britain, Russia, Korea, Japan, and Australia. 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.

What are the benefits of this drug?

More patients achieved clear or almost clear skin and a reduction in itch after treatment with ADBRY in comparison to those who were treated with placebo.

What are the benefits of this drug (results of trials used to assess efficacy)?

Table 1 below summarizes efficacy results at Week 16 for the evaluated patients in Trials 1, 2, and 3. The primary endpoint was the proportion of patients with Investigator’s Global Assessment (IGA) score of Clear (score of 0) or Almost Clear (score of 1) with at least a 2-point decrease from baseline at Week 16, comparing ADBRY-treated patients to placebo-treated patients.

Table 1. Efficacy Results at Week 16 – Trials 1, 2, and 3

Parameter	Trial 1		Trial 2		Trial 3
	ADBRY	Placebo	ADBRY	Placebo	ADBRY + TCS	Placebo + TCS
Number of subjects randomized and dosed	601	197	577	193	243	123
IGA 0 or 1a	16%	7%	21%	9%	38%	27%
Difference (95% CI)	9% (4%, 13%)		12% (6%, 17%)		11% (1%, 21%)
EASI-75b	25%	13%	33%	10%	56%	37%
Difference (95% CI)	12% (7%, 18%)		22% (17%, 28%)		20% (9%, 30%)
Number of subjects with baseline worst daily pruritus NRS (weekly average) score ≥4	594	194	563	192	240	123
Worst daily pruritus NRS (≥4‑point reduction)	20%	10%	25%	9%	46%	35%
Difference (95% CI)	10% (4%, 15%)		16% (11%, 21%)		11% (1%, 22%)

Source: Adapted from FDA Review
^aResponders was defined as proportion of subjects with an IGA 0 (clear) or 1 (almost clear).
^bResponders was defined as proportion of subjects with at least 75% reduction in EASI score from baseline
Abbreviations: CI, confidence interval; EASI-75, Eczema Area and Severity Index; IGA, investigator’s global assessment; NRS, numeric rating score; TCS, topical corticosteroids

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

• Sex: ADBRY worked similarly in male and female patients.
• Race: The number of patients of races other than White was limited; therefore, differences in response among races could not be determined.
• Age: The number of patients above 65 years of age was limited; therefore, differences in response between patients above and below 65 years of age could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 2, Table 3, and Table 4 below summarize efficacy results at Week 16 by age, sex, and race for each clinical trial.

Table 2. IGA 0/1 Response at Week 16 by Age, Sex and Race - Trial 1

Subgroups (n[A], n[P])	ADBRY N=601	Placebo N=197	Difference (95% CI)
Age, years
18 to 64 (572, 183)	16%	8%	8% (3%, 13%)
≥65 (29, 14)	17%	0%	17% (4%, 31%)
Sex
Male (350, 122)	13%	7%	7% (1%, 12%)
Female (251, 75)	20%	8%	12% (4%, 20%)
Race
White (424, 137)	18%	6%	13% (7%, 18%)
Black or African American (41, 17)	15%	29%	-15% (-39%, 9%)
Asian (120, 40)	8%	3%	5% (-2%, 12%)
Other (1, 0)	7%	-	-
Overall	16%	7%	9% (4%, 13%)

Source: Adapted from FDA Review
Abbreviations: A, ADBRY; CI, confidence interval; P, placebo

Table 3. IGA 0/1 Response at Week 16 by Age, Sex and Race - Trial 2

Subgroups (n[A], n[P])	ADBRY N=591	Placebo N=201	Difference (95% CI)
Age, years
18 to 64 (548, 186)	21%	10%	12% (6%, 17%)
≥65 (29, 7)	17%	0%	17% (4%, 31%)
Sex
Male (347, 108)	20%	10%	9% (2%, 17%)
Female (230, 85)	24%	8%	16% (8%, 24%)
Race
White (370, 123)	24%	10%	14% (7%, 21%)
Black or African American (31, 9)	19%	33%	-14% (-48%, 20%)
Asian (154, 52)	18%	6%	12% (3%, 20%)
Other (19, 9)	9%	-	-
Overall	21%	9%	11% (6%, 17%)

Source: Adapted from FDA Review
Abbreviations: A, ADBRY; CI, confidence interval; P, placebo

Table 4. IGA 0/1 Response at Week 16 by Age, Sex and Race - Trial 3

Subgroups (n[A], n[P])	ADBRY + TCS N=243	Placebo+ TCS N=123	Difference (95% CI)
Age, years
18 to 64 (231, 115)	38%	27%	11% (1%, 21%)
≥65 (12, 8)	33%	25%	8% (-32%, 49%)
Sex
Male (120, 83)	34%	23%	11% (-1%, 24%)
Female (123, 40)	41%	35%	7% (-11%, 24%)
Race
White (194, 81)	38%	32%	6% (-6%, 18%)
Black or African American (22, 12)	45%	0%	45% (25%, 66%)
Asian (17, 24)	41%	25%	16% (-13%, 45%)
Other (10, 6)	10%	17%	-7% (-42%, 28%)
Overall	38%	27%	11% (1%, 21%)

Source: Adapted from FDA Review
Abbreviations: A, ADBRY; CI, confidence interval; P, placebo; TCS, topical corticosteroids

What are the possible side effects?

The most common side effects of ADBRY in clinical trials were upper respiratory tract infection (common cold), conjunctivitis (inflammation of the outer layer of the eye), irritation at injection site, and a slight temporary increase in a type of white blood cell (eosinophils).

ADBRY can rarely cause allergic reactions (hypersensitivity), including a severe reaction known as anaphylaxis. Patients should stop using ADBRY and tell their healthcare provider or get emergency help right away if they experience any of the following symptoms: breathing problems; swelling of the face, mouth, and tongue; hives; itching; fainting, dizziness, feeling lightheaded (low blood pressure); or a skin rash.

Patients with an untreated parasitic (helminthic) infection should not be treated with ADBRY.

Patients should not receive live vaccines while being treated with ADBRY.

What are the possible side effects (results of trials used to assess safety)?

Table 5 below summarizes safety results at Week 16 for the evaluated patients in Trials 1, 2, and 3.

Table 5. Adverse Reactions Occurring in ³1% of the ADBRY Monotherapy Group or the ADBRY + TCS Group in the Atopic Dermatitis Trials Through Week 16 – Trials 1, 2, and 3

Adverse Reaction	Trial 1+2		Trial 3
	ADBRY N=1180 n (%)	Placebo N=388 n (%)	ADBRY +TCS N=243 n (%)	Placebo + TCS N=123 n (%)
Upper respiratory tract infection	281 (23.8)	79 (20.4)	73 (30.0)	19 (15.4)
Conjunctivitis	88 (7.5)	12 (3.1)	33 (13.6)	6 (4.9)
Injection site reaction	87 (7.4)	16 (4.1)	27 (11.1)	1 (0.8)
Eosinophilia	17 (1.4)	2 (0.5)	3 (1.2)	0

Source: Adapted from FDA Review
Monotherapy: pooled analysis of Trials 1 and 2
ADBRY + TCS: Analysis of Trial where subjects were on background topical corticosteroid (TCS) therapy.
Abbreviations: TCS, topical corticosteroids

Were there any differences in side effects among sex, race and age?

• Sex: The occurrence of side effects was similar in male and female patients.
• Race: The occurrence of side effects was similar in White and Black or African American patients.
• Age: The number of patients above 65 years of age was limited; therefore, differences in adverse event rates between patients above and below 65 years of age could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The results of subgroup analyses by sex, age, and race are presented in the following tables.

Table 6. AEs During the Initial Treatment Period by Sex - Trials 1 and 2 (Safety Population)

Event	ADBRY N=1194		Placebo N=396
	Female N=485	Male N=709	Female N=161	Male N=235
Any AE	337 (69.5%)	487 (68.7%)	120 (74.5%)	163 (69.4%)
Any SAE	9 (1.9%)	24 (3.4%)	5 (3.1%)	8 (3.4%)

Source: Adapted from FDA Review
Abbreviations: AE, adverse event; SAE, serious adverse event

Table 7. AEs During the Initial Treatment Period by Age - Trials 1 and 2 (Safety Population)

Event	ADBRY N=1194		Placebo N=396
	18 to 64 Years N=1135	≥65 Years N=59	18 to 64 Years N=375	≥65 Years N=21
Any AE	789 (69.5%)	35 (61.4%)	270 (72.0%)	13 (61.9%)
Any SAE	30 (2.6%)	3 (5.3%)	10 (2.7%)	3 (14.3%)

Source: Adapted from FDA Review
Abbreviations: AE=Adverse Event, SAE=Serious Adverse Event

Table 8. AEs During the Initial Treatment Period by Race - Trials 1 and 2 (Safety Population)

Event	ADBRY N=1194			Placebo N=396
	Asian N=275	Black or African American N=84	White N=797	Asian N=91	Black or African American N=34	White N=259
Any AE	185 (67.3%)	36 (42.9%)	573 (71.9%)	66 (72.5%)	19 (55.9%)	187 (72.2%)
Any SAE	5 (1.8%)	2 (2.4%)	24 (3.0%)	0	3 (8.8%)	10 (3.9%)

Source: Adapted from FDA Review
Abbreviations: AE, adverse event; SAE, serious adverse event

DEMOGRAPHIC SNAPSHOT

Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of ADBRY.

Figure 1. Baseline Demographics by Sex – Efficacy Population

Source: Adapted from FDA Review

Figure 2 summarizes the percentage of patients by race enrolled in the combined clinical trials used to evaluate the efficacy of ADBRY.

Figure 2. Baseline Demographics by Race – Efficacy Population

Source: Adapted from FDA Review
* Includes American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander and Other.

Figure 3 summarizes the percentage of patients by age enrolled in the combined clinical trials used to evaluate the efficacy of ADBRY.

Figure 3. Baseline Demographics by Age – Efficacy Population

Source: Adapted from FDA Review

Who participated in the trials?

Table 9 below summarizes demographics for the randomized subjects who were dosed (FAS population) in the clinical trials.

Table 9. Baseline Demographics - Trial 1, Trial 2, and Trial 3 (FAS1)

Demographic Subgroup	TRIAL 1		TRIAL 2		TRIAL 3
	ADBRY N=601	Placebo N=197	ADBRY N=577	Placebo N=193	ADBRY + TCS N=243	Placebo + TCS N=123
Sex, n (%)
Male	350 (58%)	122 (62%)	347 (60%)	108 (56%)	120 (49%)	83 (67%)
Female	251 (42%)	75 (38%)	230 (40%)	85 (44%)	123 (51%)	40 (33%)
Age, years
Mean (SD)	38.6 (13.7)	39.3 (15.3)	36.9 (14.7)	34.8 (14.0)	39.1 (14.7)	37.5 (14.8)
Median	37	36	34	29	37	34
Range	18 to 92	18 to 82	18 to 86	18 to 80	18 to 79	18 to 78
Age group, years, n (%)
18 to 64	572 (95%)	183 (93%)	548 (95%)	186 (96%)	231 (95%)	115 (94%)
65 to 84	28 (5%)	14 (7%)	28 (5%)	7 (4%)	12 (5%)	8 (6%)
≥85	1 (<1%)	0 (0%)	1 (<1%)	0 (0%)	0 (0%)	0 (0%)
Race2, n (%)
White	424 (71%)	137 (70%)	370 (64%)	123 (64%)	194 (80%)	81 (66%)
Black of African American	41 (7%)	17 (9%)	31 (5%)	9 (5%)	22 (9%)	12 (10%)
American Indian or Alaska Native	1 (<1%)	0 (0%)	2 (<1%)	0 (0%)	0 (0%)	0 (0%)
Native Hawaiian or other Pacific Islander	5 (1%)	0 (0%)	1 (<1%)	0 (0%)	1 (<1%)	1 (1%)
Asian	120 (20%)	40 (20%)	154 (26%)	52 (26%)	17 (7%)	24 (19%)
Other	8 (1%)	0 (0%)	19 (3%)	9 (5%)	9 (4%)	5 (4%)

Source: Adapted from FDA Review
¹ Full Analysis Set (FAS) was defined as all randomized subjects who were dosed
² Missing race information for 5 subjects in Trial 1: 2 in the ADBRY Q2W arm and 3 in the placebo arm
Abbreviations: Q2W, every two weeks; TCS, topical corticosteroids

How were the trials designed?

The benefit and side effects of ADBRY were evaluated in three clinical trials of adult patients with moderate to severe atopic dermatitis not adequately controlled by topical medication(s). In all three trials, subjects received subcutaneous injections of ADBRY 600 mg or placebo on Day 0, followed by 300 mg every other week or placebo for 16 weeks. In one of the trials, in addition to ADBRY or placebo injections, patients applied topical corticosteroids (TCS) to affected areas of the skin. Neither the participants nor the health care providers knew which injection treatment was being given until after the trials were completed but they knew which TCS was being given.

Patients were evaluated for improvement of atopic dermatitis from the first to the last day of treatment. The benefit of ADBRY to placebo was assessed after 16 weeks of treatment using the Investigator’s Global Assessment [IGA] score that measures the severity of disease on a scale from 0 to 4 for all three trials.

How were the trials designed?

The efficacy of ADBRY was evaluated in three randomized, double-blind, placebo-controlled trials. All patients had moderate to severe atopic dermatitis defined as a score of ≥3 using an Investigator’s Global Assessment (IGA) severity scale of 0 to 4, an Eczema Area and Severity Index (EASI) score ≥16 on a scale of 0 to 72, and a minimum body surface area involvement of ≥10%.

In Trials 1 and 2, patients received ADBRY or placebo injection every two weeks for 16 weeks. The trials lasted for 66 weeks. In Trial 3, patients received ADBRY or placebo injection every two weeks with concomitant topical corticosteroids (TCS) and as needed topical calcineurin inhibitors for problem areas only. Trial 3 lasted 46 weeks.

The primary efficacy outcome measure for all three trials was the proportion of patients at Week 16 who achieved success, defined as an IGA grade of Clear (score of 0) or Almost Clear (score of 1) with a 2-grade or greater improvement from baseline, comparing ADBRY-treated patients to placebo-treated patients.

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.

PRESCRIBING INFORMATION

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