Aslan Pharmaceuticals provides TREK-DX study update

ASLAN Pharmaceuticals has begun to enroll patients in the US under an updated protocol in the ongoing TREK-DX trial, studying eblasakimab in dupilumab-experienced patients with moderate-to-severe atopic dermatitis. TREK-DX is the first randomized, double-blind, placebo-controlled trial to be conducted in AD patients who have been previously treated with dupilumab, a market estimated to reach $10 billion by 20291. Based on findings from the TREK-AD study which highlighted the changing AD patient population in the US, the TREK-DX inclusion criteria have been tightened to enroll patients with a baseline Eczema Area and Severity Index score of at least 18, instead of 16. In conjunction with this, independent reviewer confirmation of baseline EASI scores has also been implemented. US sites are now enrolling patients according to the updated criteria and additional sites in Europe are on track to open in the first half of 2024. TREK-DX will enroll approximately 75 patients who have discontinued dupilumab treatment for any reason, including inadequate control of AD, loss of access or an adverse event, and treat them with either 400mg eblasakimab or placebo once weekly for 16 weeks. At the time of the data cut off for this preliminary review of blinded data from 22 patients enrolled under the original inclusion criteria, who were randomized 2:1 active to placebo, 17 patients completed the 16 week treatment period and 5 patients discontinued before the completion of the 16 week treatment period. At 16 weeks or the last visit, EASI score decreased at least 90% in 10 patients, or 45%, and 11 patients, or 50%, achieved a validated Investigator Global Assessment score of 0 or 1. Of the 9 patients who previously had an inadequate response to dupilumab, 5 patients achieved EASI-90 and 5 patients a vIGA score of 0 or 1. Treatments have been well-tolerated to date and no new safety signals were identified. There have been no reports of conjunctivitis and no reports of injection site reactions. Topline unblinded data from the full dataset is expected at the end of 2024. Translational data demonstrates differentiated effects of targeting IL-13R versus IL-4R, suggesting eblasakimab has the potential to be effective even in instances where dupilumab is not: Eblasakimab targets the IL-13 receptor subunit of the Type 2 receptor, preventing signaling through both interleukin 4 and interleukin 13. Both are key drivers of inflammation in AD, however, recently published translational data highlighted the advantages of targeting IL-13R by eblasakimab over the IL-4 receptor, the target of dupilumab, in AD patient peripheral blood mononuclear cells4. IL-13R blockade resulted in more efficient reduction of cytokines implicated in Type 2-driven inflammation compared to IL-4R blockade, as well as lower levels of Type 1 pro-inflammatory cytokines. Additional data from head-to-head studies between eblasakimab and dupilumab in skin biopsies from AD patients confirmed the differentiated effects of targeting IL-13R versus IL-4R5. In this study, eblasakimab reduced localized secretion of pro-inflammatory Type 2 cytokines by the skin tissue more efficiently than dupilumab, suggesting eblasakimab could have the potential to be effective in AD patients that do not achieve an adequate response to dupilumab.