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− Results from a pooled safety analysis of three Phase 3 trials (ECZTRA 1, 2, and ECZTRA 3), Phase 2 (ECZTRA 5) and Phase 2b trials demonstrate overall frequency of AEs with tralokinumab was comparable to placebo in the initial 16-week period in adults with moderate-to-severe atopic dermatitis1
− In an exploratory analysis of the Phase 3 ECZTRA 1 trial, treatment with tralokinumab was associated with significant reduction in S. aureus colonization compared with placebo at week 162
- Phase 2 ECZTRA 5 trial showed use of tralokinumab did not affect vaccine response rates of Tdap (combined tetanus, diphtheria, and acellular pertussis) and meningococcal vaccines3
LEO Pharma A/S, a global leader in medical dermatology, today announced data demonstrating the safety profile for tralokinumab, an investigational, fully human monoclonal antibody that specifically neutralizes the interleukin-13 (IL-13) cytokine.1 Data from a pooled analysis of three pivotal Phase 3 (ECZTRA 1, 2, and ECZTRA 3), Phase 2 (ECZTRA 5) and Phase 2b trials show overall frequency of AEs with tralokinumab was comparable to placebo in the initial 16-week period when used as a monotherapy and as a combination therapy with topical corticosteroid (TCS) mometasone furoate in adult patients with moderate-to-severe atopic dermatitis.1 Data presented include the impact of tralokinumab on S. aureus colonization, and the effects of tralokinumab on vaccine responses to Tdap and meningococcal vaccines.2,3 Results were presented online at European Academy of Dermatology and Venereology (EADV) Virtual 2020.
Tralokinumab is a fully human monoclonal antibody that specifically neutralizes the IL-13 cytokine, a key driver of the underlying chronic inflammation in atopic dermatitis in adults.4,5 It is an investigational therapy under clinical development, and its efficacy and safety are currently being evaluated by regulatory authorities.
"Since atopic dermatitis is a chronic condition that can affect people throughout their lives, studies on the safety of tralokinumab and its impact on S. aureus colonization and vaccine response are key to helping health care professionals and patients assess potential new treatment options," said Professor Thomas Werfel, MD, Head of Research, Immunodermatology and Allergy Division, and Deputy Director, Clinical Department of Dermatology and Allergy at Hannover Medical University. "I look forward to seeing additional data."
Pooled Safety Data and Conjunctivitis
In the pooled analysis (n=2,285) of five studies, tralokinumab 300 mg Q2W (every two weeks) demonstrated a safety profile comparable to placebo over 52 weeks with regard to the overall frequency and severity of adverse events, which was consistent with the initial 16-week treatment period.1
Overall frequency of adverse events (AEs) in the initial 16-week period was similar for tralokinumab (66%) compared with placebo (67%), and were recovered or resolved in 60% and 62% respectively.1 The majority were mild or moderate, and serious AEs occurred at a lower frequency for tralokinumab (2.1%) than placebo (2.8%).1 The proportion of AEs leading to permanent discontinuation up to 16 weeks of treatment was low and similar for tralokinumab and placebo (2.3% vs 2.8%).1
Data from the pooled analysis showed conjunctivitis occurred with higher frequency in patients treated with tralokinumab (n=1605) vs placebo (n=680) at a rate of 7.5% vs. 3.2%.6 Overall, 145 and 23 conjunctivitis events occurred in the tralokinumab and placebo groups, respectively.6 The majority of events were mild (68% vs 65%) or moderate (30% vs 35%) in severity and most cases resolved (78.6% vs 73.9%) or were resolving (2.8% vs 4.3%) during the initial treatment period.6 No events were serious, and two events led to permanent discontinuation of tralokinumab.6 An increased incidence of conjunctivitis was observed in patients with more severe atopic dermatitis and a prior history of allergic conjunctivitis.6
Staphylococcus Aureus (S. aureus) Colonization
Results from an exploratory analysis of a Phase 3 trial (ECZTRA 1) (n=802) showed tralokinumab 300 mg Q2W (n= 603) was associated with a significant reduction in Staphylococcus aureus (S. aureus) colonization in lesional skin compared with placebo (n=199) in adult patients with moderate-to-severe atopic dermatitis.2 Median S. aureus abundance was reduced more from baseline to week 16 in patients receiving tralokinumab (n=555) vs placebo (n=184), with a 10-fold greater reduction for tralokinumab versus placebo-treated patients.2
A Phase 2 trial (ECZTRA 5) assessing vaccine responses in adults (n=215) with moderate-to-severe atopic dermatitis who received Tdap and meningococcal vaccines found that tralokinumab 300 mg Q2W did not have an impact on vaccine response.3
The primary endpoint of vaccine response rates was high (>90% for Tdap and >84% for meningococcal vaccines), with only minor differences observed between adults treated with tralokinumab (n=107) vs adults treated with placebo (n=108).3 At 16 weeks, non-inferiority of tralokinumab vs placebo for immune responses to Tdap (91.9% vs 96.1%; treatment difference –4.2% [95% CI –11.4, 3.1]) and meningococcal (86.0% vs 84.2%; treatment difference 1.8% [95% CI –9.2, 12.8]) vaccines was demonstrated.3
During the 16-week treatment period, the overall proportion of patients reporting AEs was slightly lower for tralokinumab (45.8%) than placebo (50.5%) and most were mild (tralokinumab, 30.8% vs placebo, 30.8%) or moderate (24.3% vs 29.0%) in severity.3 Severe AEs occurred in 4.7% of patients treated with tralokinumab.3
"We’ve heard from patients around the world about the physical, psychological and social impact that atopic dermatitis places on so many adults living with this debilitating condition," said Kim Kjøller, M.D., Executive Vice President, Global Research and Development, LEO Pharma. "We are encouraged by these study results, which show that tralokinumab could be a well-tolerated treatment option for health care professionals and their patients."
About ECZTRA 1, 2, ECZTRA 3, ECZTRA 5 and Phase 2b Trials
ECZTRA 1 and ECZTRA 2 (ECZema TRAlokinumab trials Nos. 1 and 2) were randomized, double-blind, placebo-controlled, multinational 52-week trials, which included 802 and 794 adult patients, respectively, to evaluate the efficacy and safety of tralokinumab (300 mg) as monotherapy in adults with moderate-to-severe atopic dermatitis who were candidates for systemic therapy.7
ECZTRA 3 (ECZema TRAlokinumab trial No. 3) was a double-blind, randomized, placebo-controlled, multinational 32-week study, which included 380 adult patients, to evaluate the efficacy and safety of tralokinumab (300 mg) in combination with TCS in adults with moderate-to-severe atopic dermatitis who are candidates for systemic therapy.8
ECZTRA 5 (ECZema TRAlokinumab trial No. 5) was a randomized, double-blind, placebo-controlled, 30-week, Phase 2 trial which included 215 adult patients, with atopic dermatitis to evaluate the effect of tralokinumab (300 mg) on vaccine antibody responses (Tdap and meningococcal vaccines) in adults with moderate-to-severe atopic dermatitis who are candidates for systematic therapy. Patients were treated with either tralokinumab or placebo for 16 weeks. The efficacy, safety and tolerability of tralokinumab when administered with the studied vaccines was also assessed.9
Phase 2b was a randomized, double-blinded, placebo-controlled, dose-ranging clinical trial to evaluate the efficacy and safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis.13
About atopic dermatitis
Atopic dermatitis (AD) is a chronic, inflammatory, heterogeneous skin disease characterized by intense itch and eczematous lesions. Atopic dermatitis is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation. Type 2 cytokines, including IL-13, play a central role in the key aspects of atopic dermatitis pathophysiology.4,12
Tralokinumab is a fully human, high affinity immunoglobulin (Ig) G4 monoclonal antibody (mAb) that works by neutralizing the IL-13 cytokine.5 IL-13 plays a key role in driving the underlying chronic inflammation in atopic dermatitis.4, By specifically binding to the IL-13 cytokine with high affinity, tralokinumab prevents its interaction with the receptor and the subsequent downstream IL-13 signalling.5
About LEO Pharma
The company is a leader in medical dermatology with a robust R&D pipeline, a wide range of therapies and a pioneering spirit. Founded in 1908 and owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, setting new standards of care for people with skin conditions. LEO Pharma is headquartered in Denmark with a global team of 6,000 people, serving 92 million patients in 130 countries. For more information about LEO Pharma, visit www.leo-pharma.com.
MAT-37741. October 2020.
1Simpson E, et al. Safety of specifically targeting interleukin-13 with tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomised, double-blind, placebo-controlled Phase 3 and Phase 2 trials. E-poster at European Academy of Dermatology and Venereology (EADV) Virtual Congress; October 29-31, 2020. P0218; Abstract 1464.
2Bieber T, et al. Impact of targeting interleukin-13 on Staphylococcus aureus colonisation: results from a Phase 3, randomised, double-blind, placebo-controlled trial with tralokinumab in adult patients with atopic dermatitis. Oral presentation at European Academy of Dermatology and Venereology (EADV) Virtual Congress; October 29-31, 2020. Abstract 1363.
3ola J, et al. Vaccine antibody responses in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: results from the 30-week Phase 2 ECZTRA 5 trial. E-poster at European Academy of Dermatology and Venereology (EADV) Virtual Congress; October 29-31, 2020. P0181; Abstract 806.
4ber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75:54–62.
5ovic B, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017;429:208-219.
6Wollenberg A, et al. Conjunctivitis in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: pooled results from five clinical trials. E-poster at European Academy of Dermatology and Venereology (EADV) Virtual Congress; October 29-31, 2020. P0216; Abstract 1448.
7lenberg, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). British Journal of Dermatology. 2020.
8Silverberg JI, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. British Journal of Dermatology. 2020.
9ClinicalTrials.gov. National Library of Medicine (U.S.). Vaccine Responses in Tralokinumab-Treated Atopic Dermatitis - ECZTRA 5 (ECZema TRAlokinumab Trial No. 5) (ECZTRA 5). Identifier NCT03562377. https://clinicaltrials.gov/ct2/show/NCT03562377
10Weidinger S, et al. Atopic dermatitis. Lancet 2016;387:1109-1122.
11Boguniewicz M, et al. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 2011;242(1):233-46.
12Tsoi LC, et al. Atopic dermatitis is an IL-13 dominant disease with greater molecular heterogeneity compared to psoriasis. J Invest Dermatol 2019;139:1480-1489.
13ClinicalTrials.gov. National Library of Medicine (U.S.). Phase 2 Study to Evaluate the Efficacy and Safety of Tralokinumab in Adults with Atopic Dermatitis (Phase 2b). Identifier NCT02347176. https://clinicaltrials.gov/ct2/show/NCT02347176
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