Leo Pharma’s Tralokinumab Produces Sustained Improvement in AD

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Tralokinumab is a high affinity, human monoclonal antibody that specifically binds to and inhibits the IL-13 cytokine, a key driver of atopic dermatitis signs and symptoms. 

Leo Pharma’s tralokinumab 300 mg every other week plus optional topical corticosteroids (TCS) showed long-term improvements in itch, sleep, and in atopic dermatitis signs and symptoms, according to an interim analysis at 56 weeks in the ECZTEND trial that was presented at the AAD 2021 VMX.

Tralokinumab is a high affinity, human monoclonal antibody that specifically binds to and inhibits the IL-13 cytokine, a key driver of atopic dermatitis signs and symptoms. 

LEO Pharma recently received a positive opinion for tralokinumab from the Committee for Medicinal Products for Human Use of the European Medicines Agency.

“We are encouraged by the sustained improvements seen over time in patients treated with tralokinumab in the ECZTEND trial, showing great potential for a promising new treatment option for adults living with uncontrolled moderate-to-severe atopic dermatitis,” says Andrew Blauvelt, MD, MBA, President of Oregon Medical Research Center in Portland, Oregon, and lead investigator for ECZTEND, in a news release.  

Patients who had enrolled in pivotal Phase 3 trials ECZTRA 1 and 2 who continued into ECZTEND were on treatment for at least two years. 

The ongoing 268-week open-label extension trial is investigating the long-term safety and efficacy of tralokinumab 300 mg every other week in patients who previously participated in parent trials ECZTRA 1-8 and TraSki investigator-initiated study.  The primary endpoint was defined as the number of adverse events during the treatment period from baseline up to Week 268. 

Interim analysis at Week 56 included patients from parent trials ECZTRA 1, 2, ECZTRA 3 and ECZTRA 5. Interim efficacy results at Week 56 were based on the Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and at least a 75 percent improvement in the Eczema Area and Severity Index score (EASI-75). 

Participants included 1,174 patients from ECZTEND at data cut-off.  Observed outcomes for all patients enrolled 60 weeks prior to data cut-off (n=513) were analyzed at Week 56. At parent-trial baseline, ECZTEND baseline, and Week 56, median EASI score was 26.6, 4.7, and 1.8, respectively.  At Week 56, IGA and EASI response rates were 49.7 percent (IGA 0/1), 95.1 percent (EASI-50), 82.8 percent (EASI-75), 61.0 percent (EASI-90), and 79.7 percent (EASI ≤7). An EASI score of ≤7 corresponds to mild atopic dermatitis. 

At the same 56-week data cut-off, measurements of itch and sleep disruptions due to itch were also reported.  At Week 56, the mean worst weekly pruritus (i.e. itch) numeric rating scale (NRS) score was 3.3 (parent-trial baseline was 7.7) while the mean eczema-related weekly sleep NRS score was 2.0 (parent-trial baseline was 6.9). 

In the two-year cohort of patients who completed 52 weeks of tralokinumab treatment in parent studies (ECZTRA 1 and 2) and at least 56 weeks in ECZTEND (n=291), observed EASI response rates were 93.8 percent (EASI-50), 82.5 percent (EASI-75), and 59.8 percent (EASI-90), demonstrating sustained efficacy after two years of treatment. The efficacy and response rates demonstrated by this two-year cohort were consistent with that of the overall group at data cut-off (56 weeks).  These results indicate patients receiving long-term treatment with tralokinumab sustained the response rates and improvements in itch and sleep achieved in the parent trials. 

The long-term safety of tralokinumab treatment were also assessed.  By the data cut-off, 11.8 percent of patients had withdrawn from the study, and discontinuation rates due to an adverse event were low (1.6%). 

In the safety analysis set (n=1,174), from the start of the ECZTEND trial to data cut-off, 71.9 percent of patients experienced an adverse event; most were mild or moderate in severity. 4 The most frequently reported adverse events (≥5% of patients receiving tralokinumab) included viral upper respiratory tract infection (mainly reported as common cold; 21.3%), atopic dermatitis (13.5%), and upper respiratory tract infection (7.1%). Conjunctivitis was reported in 5.9 percent of patients. 

In a related study, neutralizing interleukin-13 with tralokinumab shifted the molecular phenotype of lesional skin towards that of non-lesional skin and restored skin barrier abnormalities in patients with moderate-to-severe AD. These findings were also presented at AAD VMX 2021.

Study author Emma Guttman-Yassky, MD, PhD, the Waldman Professor and System Chair at the Department of Dermatology at the Icahn School Medicine at Mount Sinai in New York analyzed skin biopsy samples from patients enrolled in the ECZTRA 1 trial, one of the three Phase 3 trials that demonstrated tralokinumab’s efficacy and safety in patients with moderate-to-severe AD.

The AD disease phenotype consists of both barrier and immune abnormalities in skin lesions.  

“It is important that a drug for atopic dermatitis is able to modulate both aspects of the skin abnormalities as tralokinumab does,” says Dr. Guttman-Yassky

About the ECZTEND - Long-Term Extension (LTE) Trial

ECZTEND is a Phase 3, long-term (up to 268 weeks), open-label, single-arm, extension trial to evaluate the safety and efficacy of tralokinumab in patients with atopic dermatitis who participated in the previous tralokinumab monotherapy trials (ECZTRA 1 and ECZTRA 2), the combination therapy tralokinumab plus TCS trial (ECZTRA 3), the Drug-drug interaction (DDI) trial (ECZTRA 4), the vaccine trial (ECZTRA 5), and the oral cyclosporine A trial (ECZTRA 7), the combination therapy tralokinumab plus TCS trial in Japanese subjects (ECZTRA 8), and the tralokinumab monotherapy skin barrier function trial (TraSki). 

About ECZTRA 1, 2, ECZTRA 3 and ECZTRA 5 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. 

ECZTRA 3 (ECZema TRAlokinumab trial No. 3) was a double-blind, randomized, placebo-controlled, multinational 32-week trial, 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. 

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 safety, efficacy, and tolerability of tralokinumab when administered with the studied vaccines was also assessed. 

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