Tralokinumab Meets Endpoints in Adolescent AD Trial

LEO Pharma announced the 16-week results from its 52-week trial, ECZTRA 6 (NCT0356861), in which the investigational therapy tralokinumab (Adtralza; LEO Pharma) as a monotherapy demonstrated significant improvement in both the primary and secondary endpoints among adolescent patients aged 12 to 17 years with moderate to severe atopic dermatitis (AD). The data from the study was presented at the 2021 Fall Clinical Dermatology Conference, held October 21 to 24 in Las Vegas, Nevada, and virtually.¹

Tralokinumab is a high-affinity, human monoclonal antibody that specifically binds to and inhibits IL-13, a key driver of atopic dermatitis signs and symptoms.^2,3 It is currently in development in the United States but has not yet been approved by the FDA. It has been approved for the treatment of adults with moderate to severe atopic dermatitis by the European Commission and the Medicines and Healthcare Products Regulatory Agency (MHRA) in June 2021 and by Health Canada in October 2021.^4,5

“After 16 weeks, adolescents who received either dose of tralokinumab, without rescue therapy, showed significantly greater improvement in atopic dermatitis signs and symptoms and quality of life compared to those receiving placebo,” said Amy Paller, MD, chair of the Department of Dermatology at the Feinberg School of Medicine, Northwestern University in Chicago, Illinois, and the international coordinating investigator for the trial. “These findings are encouraging, as moderate to severe atopic dermatitis can have major physical and psychosocial impacts on adolescents who have limited options for long-term treatment.”

The 16-week initial treatment period of the study determined the efficacy and safety of tralokinumab 150-mg (n=98) or 300-mg (n=97) every 2 weeks (Q2W) compared to placebo (n=94) in adolescent patients.¹

At week 16, tralokinumab met its primary and secondary endpoints, showing significantly more patients treated with tralokinumab achieved a clinical response, compared to placebo, defined as achieving an Investigator Global Assessment (IGA) of 0/1 and/or an improvement of Eczema Area and Severity Index (EASI) 75:¹

• Of the 150-mg arm, 21.4% (p < .001) of the patients achieved clear or almost-clear skin and so did 17.5% (p = .002) of the tralokinumab 300-mg group compared to 4.3% of placebo as measured by IGA.¹
• For the EASI 75 improvement, 28.6% (p < .001) of the tralokinumab 150-mg group and 27.8% (p = .001) of the tralokinumab 300-mg group achieved 75% or greater disease improvement from baseline compared to 6.4% placebo.¹

Secondary endpoints were all met by addressing the extent and severity of AD (SCORAD). The patients achieved at least a 4-point improvement in adolescent weekly average worst daily pruritus NRS score and health-related quality of life related to dermatological conditions (CDLQI).¹

The safety and tolerability of tralokinumab compared with placebo, when used to treat adolescent patients with moderate to severe AD, was also investigated. The overall frequency and severity of adverse events (AEs) in the trial were comparable across the treatment groups over 16 weeks (67% for tralokinumab 150-mg, 65% for tralokinumab 300-mg, and 62% for placebo).¹

The percentage of AEs, serious AEs, AEs leading to discontinuation, and conjunctivitis events were similar between both doses of tralokinumab (150-mg and 300-mg) and placebo treatment groups in the first 16 weeks. Most AEs in the 3 treatment arms were mild or moderate in severity and most of the AEs patients encountered were resolved. The safety results were consistent with the Phase 3 adult tralokinumab trials.¹

“We are encouraged by these results that advance our understanding of tralokinumab in adolescents, many of whom often struggle with the negative emotional and physical impacts of atopic dermatitis,” said Jörg Möller, MD, executive vice president of global research and development at LEO Pharma, Denmark. “This is an important milestone for the overall ECZTRA clinical trial program as we expand studies to include younger patients.”

References:

1. Paller A. Efficacy and safety of tralokinumab in adolescents with moderate-to-severe atopic dermatitis: results of the phase 3 ECZTRA 6 trial. Fall Clinical Dermatology Conference. Oct. 21-24, 2021. Poster Presentation.
2. Bieber T. Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020;75(1):54-62. doi:10.1111/all.13954.
3. Popovic B, Breed J, Rees DG, 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(2):208-219. doi:10.1016/j.jmb.2016.12.005
4. LEO Pharma announces European Commission approval of Adtralza (Tralokinumab) as the first and only treatment specifically targeting IL-13 for adults with moderate-to-severe atopic dermatitis. Businesswire. Press release. Published June 22, 2021. Accessed October 20, 2021. https://www.businesswire.com/news/home/20210621005564/en/LEO-Pharma-announces-European-Commission-approval-of-Adtralza%C2%AE-tralokinumab-as-the-first-and-only-treatment-specifically-targeting-IL-13-for-adults-with-moderate-to-severe-atopic-dermatitis
5. Health Canada approves ADTRALZA (Tralokinumab) as a treatment for adults with moderate-to-severe atopic dermatitis. BioSpace. Press release. Published October 18, 2021. Accessed October 20, 2021. https://www.biospace.com/article/health-canada-approves-adtralza-and-174-tralokinumab-as-a-treatment-for-adults-with-moderate-to-severe-atopic-dermatitis/