ASLAN Announces Positive Phase 2 Results of Eblasakimab in Dupilumab-Treated Patients With AD

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ASLAN Pharmaceuticals recently announced new positive interim results from its phase 2 study, TREK-DX, evaluating eblasakimab for the treatment of moderate to severe atopic dermatitis in adult patients previously treated with dupilumab (Dupixent: Sanofi and Regeneron). Overall, 60.0% of dupilumab-treated patients with atopic dermatitis treated with 400mg of eblasakimab weekly achieved a 90% reduction in their Eczema Area Severity Index (EASI) score after 16 weeks, and 66.7% of patients achieved a validated Investigator Global Assessment (vIGA) score of 0 (clear) or 1 (almost clear) after 16 weeks, compared to 14.3% of patients receiving placebo.¹

The primary end point of the percent change in EASI score from baseline to week 16 was statistically significant compared to placebo. Out of 15 patients receiving eblasakimab, 11 patients achieved a reduction in EASI score of at least 75% from baseline (EASI-75) compared to 14.3% (1/7) of patients receiving placebo (p=0.0431).

"Despite significant advancement in targeted atopic dermatitis (AD) therapy, we know that treatments are not one-size-fits-all. Indeed, it's clear from clinical trials and real world evidence that no treatment has 100% universal efficacy, and different mechanisms of action show a different balance of efficacy and safety for each individual patient. These intriguing interim data evaluating eblasakimab in patients with dupilumab experience (including a small number of previous inadequate responders) are part of a growing body of evidence to suggest that even with overlap in immunologic targets (in this case, IL-4 and IL-13), patients may show differential treatment responses - a lesson reminiscent of one we first received during the early days of psoriasis biologic development," said Raj Chovatiya, MD, PhD, clinical associate professor at the Rosalind Franklin University Medical School, founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, and Dermatology Times' Fall Editor in Chief.

TREK-DX is currently enrolling adult patients who have discontinued dupilumab for any reason after at least 16 weeks of treatment, including inadequate control of their atopic dermatitis, loss of access, or an adverse event. Patients who were treated with eblasakimab 400mg once a week (n=15) experienced a “rapid onset of action” in the first few weeks of treatment, including a statistically significant improvement in EASI scores by week 4 (p=0.0169) compared to placebo (n=7). By week 16, an 86.9% mean reduction in EASI scores from baseline was seen in patients treated with eblasakimab compared to a 51.2% reduction in patients treated with placebo (p=0.0059).

“We are extremely pleased to see eblasakimab delivering these spectacular results using a dosing regimen higher than we have tested previously. Most patients on eblasakimab achieved EASI-90 and vIGA of 0 or 1 after just 16 weeks of treatment, with numbers unprecedented in other biologics AD studies. Notably, in patients that previously had an inadequate response to dupilumab, two-thirds achieved EASI-90 and vIGA 0 or 1 when treated with eblasakimab,” said Carl Firth, PhD, Chief Executive Officer of ASLAN Pharmaceuticals, in the news release.

Key data points from the results include:

• 73.3% (11/15) of patients treated with eblasakimab achieved EASI-75, versus 14.3% (1/7) of patients treated with placebo (p=0.0431)
• 60.0% (9/15) of patients treated with eblasakimab achieved EASI-90, versus 14.3% (1/7) of patients treated with placebo (p=0.1278)
• 20.0% (3/15) of patients treated with eblasakimabachieved EASI-100, versus 0% (0/7) of patients treated with placebo (EASI-100 was not a pre-specified end point)
• 66.7% (10/15) of patients treated with eblasakimab achieved a vIGA score of 0 or 1, versus 14.3% (1/7) of patients treated with placebo (p=0.0750)
• 58.9% mean reduction in peak pruritus numerical rating scale (PP-NRS) score for patients treated with eblasakimab, versus a 12.9% reduction for patients treated with placebo (p=0.0015)
• 53.8% (7/13) of patients treated with eblasakimab, with a baseline score of at least 4, achieved a 4-point reduction in PP-NRS score, versus 14.3% (1/7) of patients treated with placebo (p=0.2460)

Additionally, of the 6 patients treated with eblasakimab who previously had an inadequate response to dupilumab, 66.7% (4/6) achieved EASI-90 and 66.7% (4/6) achieved a vIGA score of 0 or 1. Treatment with eblasakimab was well tolerated and no new safety signals were reported.

"Eblasakimab may indeed find its own unique niche of patients as we see further clinical development and a potential approval, but for now, the results from TREX-DX are especially interesting as we look to position therapies in relation to dupilumab, our first and most commonly used advanced therapy - which works well for many but not all patients. These data show that blocking IL-13R1 may be an effective and novel strategy to drive early and deep clearance in moderate-severe AD patients by targeting a key receptor complex in type 2 inflammation," concluded Chovatiya.

According to ASLAN, the TREK-DX recruitment criteria were revised in October 2023 to only enroll patients with a baseline EASI score of 18 or above. The new criteria will be the basis of analysis in the topline readout expected at the end of 2024.²

References

1. ASLAN Pharmaceuticals Announces positive interim results from phase 2 study of eblasakimab in dupilumab-experienced atopic dermatitis patients. News release. ASLAN Pharmaceuticals. April 22, 2024. Accessed April 23, 2024. https://ir.aslanpharma.com/news-releases/news-release-details/aslan-pharmaceuticals-announces-positive-interim-results-phase-2
2. ASLAN Pharmaceuticals to co-host KOLpanel discussion on changes in the clinical trial and treatment landscape for atopic dermatitis. News release. ASLAN Pharmaceuticals. October 18, 2023. Accessed April 23, 2024. https://ir.aslanpharma.com/news-releases/news-release-details/aslan-pharmaceuticals-co-host-kol-panel-discussion-changes