TRIALISTMD Β· Drug Intelligence Platform
FDA APPROVED 2021
IL-13 Antagonist Β· IgG4 mAb Β· Dermatology Β· Atopic Dermatitis
Tralokinumab-ldrm
ADBRYβ’ Β· LEO Pharma A/S
A fully human IgG4 monoclonal antibody that selectively neutralizes interleukin-13 (IL-13), a key Th2 cytokine driving atopic dermatitis. The first selective IL-13 antagonist approved in the US β and the second systemic biologic for moderate-to-severe AD β based on three pivotal Phase 3 trials (ECZTRA 1, ECZTRA 2, and ECZTRA 3).
Drug Overview
BLA 761180Indication
Moderate-to-Severe AD
Adults inadequately controlled by topical therapies
Mechanism
IL-13 Selective Antagonist
Fully human IgG4 monoclonal antibody Β· 147 kDa
Approved Dose
300 mg Q2W
Loading 600 mg at Week 0 Β· SC injection
Q4W Option
After Week 16
Patients <100 kg achieving IGA 0/1 (“clear”/”almost clear”)
Mechanism of Action
Tralokinumab-ldrm is a human IgG4 monoclonal antibody that specifically binds human interleukin-13 (IL-13) and inhibits its interaction with the IL-13 receptor Ξ±1 and Ξ±2 subunits (IL-13RΞ±1 and IL-13RΞ±2). IL-13 is a key cytokine of the Type 2 (Th2) immune response. By blocking the IL-13RΞ±1/IL-4RΞ± receptor complex, tralokinumab inhibits IL-13βinduced downstream signaling, proinflammatory cytokine and chemokine release, and IgE production β all central to the pathophysiology of atopic dermatitis.
Binds Free IL-13
High-affinity binding to circulating IL-13 cytokine
β
Receptor Blockade
Blocks IL-13RΞ±1 and IL-13RΞ±2; prevents IL-13RΞ±1/IL-4RΞ± complex signaling
β
Th2 Suppression
β cytokines, β chemokines (CCL17/18/26), β IgE; suppressed Th17/Th22 genes
β
Skin Restoration
β Keratin 16, β Ki-67; β Loricrin (barrier protein)
Selectivity vs. dupilumab: Unlike dupilumab (which blocks IL-4RΞ±, inhibiting both IL-4 and IL-13 signaling), tralokinumab exclusively targets IL-13. It does not directly inhibit IL-4 signaling. The clinical implications of this selectivity β including its relationship to the conjunctivitis risk seen with both agents β remain under investigation.
Pharmacodynamic Biomarkers
TARC/CCL17 β
Periostin β
IL-22 β
LDH β
Serum IgE β
Keratin 16 β
Ki-67 β
CCL18 β
CCL26 β
Loricrin β
Drug Identity
| Generic Name | Tralokinumab-ldrm |
| Brand Name | ADBRYβ’ |
| Drug Class | Interleukin-13 (IL-13) antagonist; fully human IgG4 monoclonal antibody |
| Antibody Isotype | Human IgG4; 1,326 amino acids; molecular weight ~147 kDa |
| Production | Mouse myeloma (NS0) cells by recombinant DNA technology |
| Sponsor / Manufacturer | LEO Pharma A/S (Ballerup, Denmark) Β· Distributed by LEO Pharma Inc. (Madison, NJ, USA) |
| Formulation | 150 mg/mL sterile, preservative-free solution Β· Single-dose prefilled syringe with needle guard (27G Γ Β½ inch, siliconized Type-1 glass) Β· pH ~5.5 |
| Inactive Ingredients | Acetic acid (0.3 mg), polysorbate 80 (0.1 mg), sodium acetate trihydrate (6 mg), sodium chloride (5 mg), water for injection |
| NDC Numbers | 50222-346-02 (2-syringe carton) Β· 50222-346-04 (4-syringe multipack) |
| BLA / Approval | BLA 761180 Β· Initial US Approval December 2021 Β· 351(a) NME |
Competitive Landscape
| Drug | Target | Approval Date | Dose | Population |
|---|---|---|---|---|
| Dupilumab (DUPIXENT) | IL-4RΞ± (IL-4/IL-13 dual) | March 28, 2017 | 300 mg Q2W SC | Adults & pediatric β₯6 months |
| Tralokinumab (ADBRY) | IL-13 selective | December 2021 | 300 mg Q2W SC | Adults only |
| Lebrikizumab (EBGLYSS) | IL-13 selective | September 13, 2023 | 250 mg Q2W SC | Adults & adolescents β₯12 years |
Sources: FDA prescribing information (BLA 761180) and FDA Medical Review (Ref ID 4909926).
Clinical Efficacy
ECZTRA 1 Β· ECZTRA 2 Β· ECZTRA 3Co-Primary Endpoints
IGA 0/1 & EASI-75
Both assessed at Week 16
Trial Design
RCT, DB, PC
3 Phase 3 trials; up to 52 weeks
Total Efficacy Population
1,934
Adults β₯18 years Β· moderate-to-severe AD
Entry Criteria
IGA β₯3 Β· EASI β₯16
BSA β₯10% Β· inadequate topical response
ECZTRA 1 β Primary Endpoint Results
NCT03131648 Β· MONOTHERAPY Β· 52 WEEKSECZTRA 1 (LP0162-1325 Β· NCT03131648) Β· n=802 randomized (800 dosed) Β· 5 countries Β· ADBRY 300 mg Q2W vs. Placebo Β· IGA 0/1 at Week 16
Difference from placebo: +9% (95% CI: 4%β13%) Β· p<0.001
ECZTRA 1 Β· EASI-75 (β₯75% improvement from baseline) at Week 16
Difference from placebo: +12% (95% CI: 6%β18%) Β· p<0.001
ECZTRA 2 β Primary Endpoint Results
NCT03160885 Β· MONOTHERAPY Β· 52 WEEKSECZTRA 2 (LP0162-1326 Β· NCT03160885) Β· n=772 randomized (770 dosed) Β· 9 countries Β· ADBRY 300 mg Q2W vs. Placebo Β· IGA 0/1 at Week 16
Difference from placebo: +12% (95% CI: 7%β17%) Β· p<0.001
ECZTRA 2 Β· EASI-75 at Week 16
Difference from placebo: +22% (95% CI: 17%β28%) Β· p<0.001
ECZTRA 3 β Primary Endpoint Results
NCT03363854 Β· COMBINATION WITH TCS Β· 32 WEEKSECZTRA 3 (LP0162-1339 Β· NCT03363854) Β· n=368 randomized & dosed Β· 8 countries Β· ADBRY 300 mg Q2W + TCS vs. Placebo + TCS Β· IGA 0/1 at Week 16
Difference from placebo: +11% (95% CI: 1%β21%) Β· p=0.025
ECZTRA 3 Β· EASI-75 at Week 16
Difference from placebo: +20% (95% CI: 9%β30%) Β· p<0.001
Key Secondary & Maintenance Endpoints
| Endpoint | ECZTRA 1 (ADBRY) | ECZTRA 2 (ADBRY) | ECZTRA 3 (ADBRY+TCS) |
|---|---|---|---|
| Pruritus NRS β₯4-point β at Week 16 | 20% vs. 10% pbo | 25% vs. 9% pbo | 46% vs. 35% pbo+TCS |
| IGA 0/1 maintained at Week 52 (Q2W arm) | 51% | 60% | 89% at Week 32 |
| IGA 0/1 maintained at Week 52 (Q4W arm) | 39% | 50% | 76% at Week 32 |
| EASI-75 maintained at Week 52 (Q2W arm) | 60% | 57% | 92% at Week 32 |
| EASI-75 maintained at Week 52 (Q4W arm) | 49% | 55% | 90% at Week 32 |
| EASI-75 maintained at Week 52 (Placebo arm) | 33% | 20% | β |
Maintenance analyses restricted to Week 16 responders re-randomized at Week 16. ECZTRA 3 continuation period 16β32 weeks. All analyses: CMH test stratified by region and baseline IGA. Non-responders/rescue medication recipients counted as non-responders. TCS = mometasone furoate 0.1% cream as needed.
Baseline Demographics
TABLE 12 Β· ECZTRA-1, ECZTRA-2, ECZTRA-3 (FAS)
Source: Table 12 β Demographics, Trials ECZTRA-1, ECZTRA-2, and ECZTRA-3 (Full Analysis Set). FDA Integrated Medical Review, BLA 761180 (Ref ID: 4784656), p. 43β44. FAS = all randomized subjects who were dosed. Sites 423, 435 (ECZTRA-2) and 818 (ECZTRA-3) excluded per statistical reviewer.
| Parameter | ECZTRA 1 | ECZTRA 2 | ECZTRA 3 (+TCS) | |||
|---|---|---|---|---|---|---|
| ADBRY Q2W (N=601) | Placebo (N=197) | ADBRY Q2W (N=577) | Placebo (N=193) | ADBRY+TCS (N=243) | Placebo+TCS (N=123) | |
| Sex | ||||||
| Male, n (%) | 350 (58%) | 122 (62%) | 347 (60%) | 108 (56%) | 120 (49%) | 83 (67%) |
| Female, n (%) | 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 | 18β92 | 18β82 | 18β86 | 18β80 | 18β79 | 18β78 |
| 18β64 years, n (%) | 572 (95%) | 183 (93%) | 548 (95%) | 186 (96%) | 231 (95%) | 115 (94%) |
| 65β84 years, n (%) | 28 (5%) | 14 (7%) | 28 (5%) | 7 (4%) | 12 (5%) | 8 (6%) |
| β₯85 years, n (%) | 1 (<1%) | 0 | 1 (<1%) | 0 | 0 | 0 |
| Race | ||||||
| White, n (%) | 424 (71%) | 137 (70%) | 370 (64%) | 123 (64%) | 194 (80%) | 81 (66%) |
| Asian, n (%) | 120 (20%) | 40 (20%) | 154 (26%) | 52 (26%) | 17 (7%) | 24 (19%) |
| Black / African American, n (%) | 41 (7%) | 17 (9%) | 31 (5%) | 9 (5%) | 22 (9%) | 12 (10%) |
| Other / Not reported | 16 (3%) | 3 (2%) | 22 (4%) | 9 (5%) | 10 (4%) | 6 (5%) |
Missing race data for 5 subjects in ECZTRA-1 (2 ADBRY, 2 placebo). Abbreviations: FAS, full analysis set; Q2W, every 2 weeks; TCS, topical corticosteroids. Source: FDA Statistical Reviewer analysis, Table 12, BLA 761180 (Ref ID: 4784656).
Baseline Disease Characteristics
TABLE 13 Β· ECZTRA-1, ECZTRA-2, ECZTRA-3 (FAS)
Source: Table 13 β Baseline Disease Characteristics, Trials ECZTRA-1, ECZTRA-2, and ECZTRA-3 (Full Analysis Set). FDA Integrated Medical Review, BLA 761180 (Ref ID: 4784656), p. 45. Entry criteria: IGA β₯3 at screening and baseline; EASI β₯16 at baseline; BSA β₯10%.
| Characteristic | ECZTRA 1 | ECZTRA 2 | ECZTRA 3 (+TCS) | |||
|---|---|---|---|---|---|---|
| ADBRY Q2W (N=601) | Placebo (N=197) | ADBRY Q2W (N=577) | Placebo (N=193) | ADBRY+TCS (N=243) | Placebo+TCS (N=123) | |
| IGA Score at Baseline | ||||||
| IGA 3 β Moderate, n (%) | 296 (49%) | 95 (48%) | 296 (51%) | 93 (48%) | 127 (52%) | 64 (52%) |
| IGA 4 β Severe, n (%) | 305 (51%) | 102 (52%) | 281 (49%) | 100 (51%) | 116 (48%) | 59 (48%) |
| EASI Score at Baseline | ||||||
| Mean (SD) | 32.2 (13.7) | 32.9 (13.9) | 32.4 (14.3) | 33.1 (13.8) | 29.1 (12.0) | 30.4 (12.9) |
| Median | 28.2 | 30.3 | 28.6 | 30.8 | 25.4 | 26.2 |
| Range | 16β72 | 16β70.8 | 15.4β72 | 16β72 | 15.8β68.4 | 16.1β72 |
| Worst Daily Pruritus NRS (Weekly Average) at Baseline | ||||||
| Mean (SD) | 7.7 (1.4) | 7.7 (1.4) | 7.9 (1.5) | 8.0 (1.3) | 7.7 (1.5) | 7.9 (1.5) |
| Median | 7.9 | 7.9 | 8.0 | 8.1 | 8.0 | 8.0 |
| NRS β₯4, n (%) | 594 (99%) | 194 (98%) | 563 (98%) | 192 (99%) | 240 (99%) | 123 (100%) |
| Body Surface Area (BSA) at Baseline (%) | ||||||
| Mean (SD) | 52.7 (24.1) | 54.4 (25.5) | 53.2 (25.4) | 54.3 (24.6) | 47.9 (23.6) | 49.1 (26.1) |
| Median | 50 | 53 | 50 | 50 | 42 | 40 |
| Range | 10β100 | 10β100 | 10β100 | 11β100 | 11β100 | 12β100 |
Abbreviations: BSA, body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; NRS, numeric rating scale; Q2W, every 2 weeks; SD, standard deviation; TCS, topical corticosteroids. Source: Table 13, FDA Medical Review BLA 761180 (Ref ID: 4784656).
Pooled Baseline Summary
ECZTRA 1 + ECZTRA 2 + ECZTRA 3Mean Age
37 yrs
Range 18β92 years across trials
Sex (Male)
58%
Across ECZTRA 1 & 2 monotherapy
IGA 3 / IGA 4
50% / 50%
Equal moderate and severe disease
Mean EASI
~32
Scale 0β72; entry criterion β₯16
Mean BSA
~53%
Extensive disease; range 10β100%
Mean Pruritus NRS
7.7β8.0
Severe itch; 98β100% had NRS β₯4
Asthma (Comorbidity)
39%
Reflecting atopic march
Hay Fever
49%
Comorbid allergic rhinitis
Food Allergy
36%
Comorbid at baseline
Allergic Conjunctivitis
21%
Baseline comorbidity β important for AE interpretation
Pooled comorbidity data from the safety population (n=1,964 treated with ADBRY across 5 trials including dose-finding and vaccine-response trials). Source: Section 6.1, ADBRY Prescribing Information (BLA 761180, Ref ID: 4911283).
Contraindications
- Known hypersensitivity to tralokinumab-ldrm or any excipients in ADBRY
Warnings & Precautions
Hypersensitivity (5.1)
Anaphylaxis and angioedema reported. Discontinue immediately and initiate appropriate therapy if serious hypersensitivity reaction occurs.
Conjunctivitis & Keratitis (5.2)
Both more frequent vs. placebo. Advise patients to report new or worsening eye symptoms. Most cases resolved or were resolving during treatment.
Helminth Infections (5.3)
IL-13 inhibition may impair anti-helminthic immunity. Treat pre-existing infections before initiation. Discontinue ADBRY if active infection during treatment fails anthelmintic therapy.
Live Vaccines (5.4)
Avoid live vaccines. Complete age-appropriate vaccinations prior to starting ADBRY. Non-live vaccine responses (Tdap, meningococcal) preserved in clinical studies.
Common Adverse Reactions β Weeks 0β16
TABLE 1 Β· ECZTRA 1+2 MONOTHERAPY POOLADBRY 300 mg Q2W (N=1,180) vs. Placebo (N=388) β Pooled ECZTRA 1 + ECZTRA 2 β Weeks 0β16
URTI cluster: URTI, viral URTI, pharyngitis, nasopharyngitis. Conjunctivitis cluster includes allergic conjunctivitis. ISR cluster: pain, erythema, swelling.
Conjunctivitis & Keratitis β Detailed Data
| Event | ADBRY | Placebo | Notes |
|---|---|---|---|
| Conjunctivitis (incl. allergic) β initial 16 wks (pool of 5 trials) | 7.5% | 3.1% | 29 vs. 12 events/100 PY; 126 subjects, 145 events; 114 resolved; 2 discontinuations |
| Conjunctivitis β maintenance Wk 16β52 (Q2W) | 8.9% | β | 20 events/100 PY; 1 severe event; 1 discontinuation |
| Conjunctivitis β maintenance Wk 16β52 (Q4W) | 6.3% | β | 14 events/100 PY |
| Keratitis (incl. keratoconjunctivitis) β initial 16 wks | 0.5% | 0% | Incl. 1 ulcerative keratitis; 9 subjects, 10 events; 5 resolved; none serious or led to discontinuation |
| Keratitis β maintenance Wk 16β52 (Q2W) | 0.6% | β | 1 subject (ulcerative, severe; resolved after discontinuation); 1.2/100 PY |
| Keratoconjunctivitis β maintenance (Q2W) | 1.9% | β | 3 subjects; not serious/severe; resolved; no discontinuations; 3.6/100 PY |
Clinical note β conjunctivitis & atopic comorbidity: At baseline, 21% of the safety population had pre-existing allergic conjunctivitis; 56% of subjects in the tralokinumab arm who developed conjunctivitis events had a prior history of allergic conjunctivitis or keratoconjunctivitis. This substantially complicates attribution. The mechanism may relate to IL-13 signaling in the conjunctiva, though this remains under investigation.
Eosinophilia & Immunogenicity
| Parameter | ADBRY | Placebo | Notes |
|---|---|---|---|
| Eosinophilia >5,000 cells/mcL β initial 16 wks | 1.2% | 0.3% | Mean/median increase from baseline to Week 4: +190 / +100 cells/mcL; declined to baseline with continued treatment |
| ADA β initial 16 weeks | 1.4% | 1.3% | Similar ADA incidence between arms |
| Neutralizing antibodies β initial 16 wks | 0.1% | 0.2% | |
| ADA β across all periods | 4.6% | β | Persistent ADA 0.9%; neutralizing antibodies 1.0% |
| ADA clinical impact | β | No clinically meaningful differences in PK, safety, or efficacy in ADA-positive patients | |
Discontinuation Rates
| Trial / Period | ADBRY | Placebo | Leading Reasons |
|---|---|---|---|
| ECZTRA 1+2 monotherapy β Wk 0β16 | 0.7% | 0% | Injection site reaction (0.3%), eosinophilia (0.3%) |
| ECZTRA 3 (+TCS) β Wk 0β16 | 0.8% | 0% | Injection site reaction (0.4%), conjunctivitis (0.4%) |
Mechanism of Action
| Target | Interleukin-13 (IL-13) β Th2 immune response cytokine |
| Specificity | Selective IL-13 neutralization; does NOT block IL-4 (cf. dupilumab = dual IL-4/IL-13 via IL-4RΞ±) |
| Receptor Blockade | Inhibits IL-13RΞ±1 and IL-13RΞ±2 interactions; specifically blocks the IL-13RΞ±1/IL-4RΞ± signaling complex |
| Downstream Effects | β proinflammatory cytokines, β chemokines (CCL17, CCL18, CCL26), β IgE; suppression of Th2, Th17, and Th22 pathway gene expression in lesional AD skin |
| Antibody Class | Fully human IgG4 monoclonal antibody Β· 1,326 amino acids Β· ~147 kDa Β· NS0 mouse myeloma cells |
Pharmacokinetics
Bioavailability (SC)
76%
Absolute bioavailability after SC administration
tmax
5β8 days
Time to maximum concentration after SC dose
Half-life
3 weeks
Terminal elimination half-life
Volume of Distribution
~4.2 L
Central compartment Vd
Systemic Clearance
0.149 L/day
Estimated CL at steady state
Steady-State Trough
~99 mcg/mL
Mean (range 98β101) at 300 mg Q2W
Time to Steady-State
Week 16
With 600 mg loading + 300 mg Q2W
Dose Proportionality
Linear
Up to 2,100 mg (30 mg/kg IV; 3.5Γ MRHD)
Metabolism
Catabolic
Proteolytic degradation to small peptides; no CYP interactions
PK Special Populations
| Body Weight (>100 kg) | Exposure decreases with increasing weight. At 300 mg Q4W, median AUC in patients >100 kg is ~1.46-fold lower vs. <100 kg β basis for Q4W restriction to patients <100 kg only |
| Age (18β92 yrs) | No clinically significant PK differences |
| Sex | No clinically significant PK differences |
| Renal Impairment | No significant PK changes in mildβmoderate impairment; severe renal impairment not studied |
| Hepatic Impairment | No significant PK changes in mild impairment; moderateβsevere not studied |
| Drug Interactions | Not formally assessed; no CYP-based interactions expected |
Pharmacodynamics
Vaccine immunogenicity: In a dedicated vaccine-response trial, antibody responses to tetanus, diphtheria, acellular pertussis (Tdap), and meningococcal vaccines were assessed at Week 12 of ADBRY treatment. Responses were similar to placebo-treated subjects. Immune responses to other vaccines were not assessed.
| Systemic biomarkers β | TARC/CCL17, periostin, IL-22, lactate dehydrogenase (LDH), serum IgE |
| Skin tissue biomarkers | β Keratin 16 (epidermal proliferation), β Ki-67; β Loricrin (barrier protein) |
| Gene expression (skin) | Suppression of Th2 pathway genes: CCL17, CCL18, CCL26; suppression of Th17/Th22-regulated markers in lesional skin |
| Eosinophil kinetics | Transient increase peaking ~Week 4 (mean +190 cells/mcL, median +100 cells/mcL); declines to baseline levels with continued treatment |
Dosing Regimen
Loading Dose (Week 0)
600 mg SC
Four 150 mg injections at different sites within the same body area
Maintenance Dose
300 mg Q2W
Two 150 mg injections; begin at Week 2
Optional Q4W Interval
After Week 16
Only for patients <100 kg achieving IGA 0/1 (“clear” or “almost clear”)
| Administration Route | Subcutaneous injection β thigh, abdomen (avoid 5 cm periumbilical zone), or upper arm (caregiver only) |
| Injection Sites | Multiple sites within the same body area per dose; rotate body area with each subsequent dose set; avoid tender, damaged, bruised, or scarred skin; individual injections β₯1 inch (3 cm) apart |
| Injection Angle | ~45Β° to skin surface; pinch fold of skin before inserting |
| Room Temp Warm-up | 30 minutes before injection; allow to reach 20β25Β°C (68β77Β°F); do not microwave, heat, or shake |
| Missed Dose | Administer as soon as possible; resume original schedule thereafter |
| Self-Injection | Permitted after training; first injection under HCP supervision |
| Concomitant TCS | May be used with or without TCS; topical calcineurin inhibitors reserved for problem areas (face, neck, intertriginous, genital) |
| Live Vaccines | Avoid; complete age-appropriate vaccinations prior to initiating therapy |
Storage & Formulation
| Formulation | 150 mg/mL β clear to opalescent, colorless to pale yellow solution; sterile, preservative-free; pH ~5.5; siliconized Type-1 glass syringe, no latex |
| Refrigerated Storage | 2β8Β°C (36β46Β°F); original carton; protect from light; do not freeze or shake |
| Room Temp Stability | Up to 25Β°C (77Β°F) for β€14 days after removal from refrigerator; discard if not used within 14 days |
| Pack Sizes | 2-syringe carton (NDC 50222-346-02) Β· 4-syringe multipack (NDC 50222-346-04) |
| Single-Dose Only | No preservatives β discard any unused product remaining in prefilled syringe |
Special Populations
| Pediatric Use | Safety and effectiveness not established in pediatric patients; PREA pediatric trials deferred (ages 6 monthsβ18 years) |
| Geriatric Use | No dose adjustment needed; limited data in patients β₯65 years (n=77 in initial treatment period); no significant PK differences by age |
| Pregnancy | Limited human data; IgG antibodies cross the placental barrier. Animal studies at up to 10Γ MRHD (IV in cynomolgus monkeys) showed no adverse developmental effects through 6 months of infant age |
| Lactation | No human milk data available; consider clinical benefit vs. potential risk |
| Renal Impairment | No dose adjustment for mildβmoderate; severe renal impairment not studied |
| Hepatic Impairment | No dose adjustment for mild impairment; moderateβsevere not studied |
| Weight β₯100 kg | Q4W interval not recommended β median AUC ~1.46-fold lower vs. <100 kg; maintain Q2W dosing |
Regulatory History
BLA 761180APRIL 27, 2020
Initial BLA 761180 Submission
LEO Pharma A/S submitted BLA 761180 under 351(a) of the Public Health Service Act for treatment of moderate-to-severe atopic dermatitis in adults
APRIL 23, 2021
FDA Complete Response Letter (CRL) β Cycle 1
CRL issued by CDRH due to insufficient needle-safety performance data for the accessorized pre-filled syringe (APFS), not for clinical efficacy or safety concerns. Review team concluded substantial evidence of effectiveness with no safety issues precluding approval.
JULY 2, 2021
BLA 761180 Resubmission (Cycle 2 / SDN 41)
Applicant resubmitted with final finished combination product needle safety performance testing (95% confidence / 99% reliability); 24-month real-time aged samples; updated 120-day safety data (data cut-off 3/31/2021) confirming no new safety concerns
OCTOBER 13, 2021
CDRH Review β Combination Product Approvable
ICC review memorandum confirmed no outstanding deficiencies; combination product (APFS) approvable
DECEMBER 22, 2021
FDA Integrated Review Memorandum
Clinical reviewer: Hamid Tabatabai, MD. Team Leader: David Kettl, MD. Concluded favorable benefit-risk with appropriate labeling for moderate-to-severe atopic dermatitis in adults
DECEMBER 2021
FDA Approval β ADBRYβ’ (tralokinumab-ldrm)
Approved for 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. Second systemic biologic approved for AD; first selective IL-13 antagonist in the US.
FDA Review Assessment
Reviewer conclusion: The Phase 3 program (ECZTRA 1, 2, and 3) showed statistically significant improvement in both co-primary endpoints (IGA 0/1 and EASI-75 at Week 16) in all three trials. The review team concluded there was substantial evidence to support the effectiveness of tralokinumab and did not identify safety issues that might impact approval.
Initial CRL context: The Complete Response in Cycle 1 was issued solely on device/combination product grounds (needle safety). Clinical efficacy and safety were not objections to approval.
Initial CRL context: The Complete Response in Cycle 1 was issued solely on device/combination product grounds (needle safety). Clinical efficacy and safety were not objections to approval.
Pediatric Plan
PREA Requirements: Because tralokinumab is a new active ingredient, a pediatric assessment was required under the Pediatric Research Equity Act (21 U.S.C. 355c). Studies were conducted in adults only. Per the agreed iPSP (June 2018): partial waiver for <6 months (impractical); Phase 3 trials in pediatric patients ages 6 months to <18 years were deferred.
Key Drug Information
| Parameter | Detail |
|---|---|
| Proprietary Name | ADBRYβ’ |
| INN / Generic Name | Tralokinumab-ldrm |
| Sponsor / Manufacturer | LEO Pharma A/S (Industriparken 55, DK-2750 Ballerup, Denmark) Β· US License No. 2169 |
| US Distributor | LEO Pharma Inc., Madison, NJ 07940, USA |
| BLA Type | 351(a) Biologics License Application β Standard Review β New Molecular Entity |
| NDC Numbers | 50222-346-02 (2-syringe carton) Β· 50222-346-04 (4-syringe multipack) |
| Formulation | 150 mg/mL solution Β· prefilled syringe Β· 27G Γ Β½ inch needle Β· siliconized Type-1 glass Β· no latex |
| BCS Class | N/A (biological / monoclonal antibody) |
| Storage | 2β8Β°C; original carton; β€25Β°C β€14 days after removal; do not freeze or shake |
| PI Revision Date | December 2021 |
| Reference IDs | 4911283 (Prescribing Information) Β· 4909926 (Integrated Medical Review) |
Data sourced from: FDA Prescribing Information for ADBRY (tralokinumab-ldrm) β BLA 761180 (Ref ID: 4911283, revised 12/2021) and FDA Integrated Medical Review β BLA 761180, SDN 41 (Ref ID: 4909926, memorandum date December 22, 2021). Clinical Reviewer: Hamid Tabatabai, MD. For investigational and educational purposes only. Not for clinical decision-making.
