AD Pipeline Watch: Eblasakimab Monthly Dosing Shows Promise in Phase 2b AD Study

With eblasakimab, once-monthly dosing from initiation is comparable to once every two weeks.

ASLAN Pharmaceuticals’ eblasakimab met the primary endpoint of percent change from baseline in the Eczema Area and Severity Index (EASI) score at week 16 versus placebo in adult patients with moderate-to-severe atopic dermatitis (AD), according to results from the Phase 2b dose-ranging TREK-AD (TRials with EblasaKimab in Atopic Dermatitis) study. 

The study medication reached statistical significance in three dosing arms: 600mg dosed once every 4 weeks (600mg Q4W), which was numerically the best performing arm, 400mg dosed once every 2 weeks (400mg Q2W) and 300mg dosed once every 2 weeks (300mg Q2W).

Eblasakimab is a novel monoclonal antibody targeting the IL-13 receptor subunit of the Type 2 receptor, a key pathway driving several allergic inflammatory diseases. Eblasakimab’s unique mechanism of action has been observed to enable specific blockade of the Type 2 receptor, preventing signaling through both interleukin 4 (IL-4) and interleukin 13 (IL-13) – the key drivers of inflammation in AD, while sparing the Type 1 receptor.

“This is the first time we’ve seen a once-a-month treatment option deliver competitive efficacy data, which would be a game-changer for patients with AD,” says Eric L. Simpson, M.D., Frances J. Storrs Professor of Medical Dermatology at the Oregon Health and Science University and Lead Investigator in the TREK-AD study, in a news release. “We haven’t seen much in the way of advancement since the launch of dupilumab, and there remains a huge unmet burden of disease experienced by patients. These results support eblasakimab’s potential to be a leading therapy for the treatment of AD, if approved.”

In the TREK-AD Phase 2b study, 289 patients were randomized and treated in the intent-to-treat (ITT) population across five dosing arms in a 1:1:1:1:1 ratio to receive one of four doses of eblasakimab (300mg Q2W, 400mg Q2W, 400mg Q4W and 600mg Q4W) or placebo for 16 weeks. Key efficacy endpoints, including EASI-75 and a validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) score of 0/1, the relevant endpoints for regulatory approval in Europe and the US respectively, are shown below:

Patients treated with eblasakimab 600mg Q4W, 400mg Q2W and 300mg Q2W saw a rapid onset of action in the first few weeks of treatment, with a statistically significant improvement in EASI score by week 4. Clinically meaningful improvements were achieved in other key efficacy measures compared to placebo (n=57) after 16 weeks of treatment, including:

Eblasakimab 600mg Q4W (n=59)

• 62.7% of eblasakimab treated patients achieved a reduction of at least 75% from baseline (EASI-75), compared to 30.7% on placebo (p=0.0041).
• 34.1% of eblasakimab treated patients achieved a reduction of at least 90% from baseline (EASI-90), compared to 10.1% on placebo (p=0.0088).
• 31.2% of eblasakimab treated patients achieved vIGA-AD score of 0 or 1 (clear or nearly clear skin), compared to 15.1% with placebo (p=0.0502).
• 73.0% least squares (LS) mean reduction in EASI score from baseline, compared to 51.1% on placebo (p=0.0010).

Eblasakimab 400mg Q2W (n=56)

• 54.5% of eblasakimab treated patients achieved EASI-75, compared to 30.7% on placebo (p=0.0322).
• 32.6% of eblasakimab treated patients achieved EASI-90, compared to 10.1% on placebo (p=0.0139).
• 32.6% of eblasakimab treated patients achieved vIGA-AD score of 0 or 1, compared to 15.1% with placebo (p=0.0380).
• 65.8% LS mean reduction in EASI score from baseline, compared to 51.1% on placebo (p=0.0294).

Eblasakimab 300mg Q2W (n=58)

• 60.7% of eblasakimab treated patients achieved EASI-75, compared to 30.7% on placebo (p=0.0064).
• 37.7% of eblasakimab treated patients achieved EASI-90, compared to 10.1% on placebo (p=0.0033).
• 33.1% of eblasakimab treated patients achieved vIGA-AD score of 0 or 1, compared to 15.1% with placebo (p=0.0327).
• 69.8% LS mean reduction in EASI score from baseline, compared to 51.1% on placebo (p=0.0050).

Eblasakimab 400mg Q4W (n=59)

The eblasakimab 400mg Q4W dosing arm did not meet the primary or secondary endpoints with statistical significance.

• 51.9% of eblasakimab treated patients achieved EASI-75, compared to 30.7% on placebo (p=0.0556).
• 24.3% of eblasakimab treated patients achieved EASI-90, compared to 10.1% on placebo (p=0.0949).
• 15.0% of eblasakimab treated patients achieved vIGA-AD score of 0 or 1, compared to 15.1% with placebo (p=0.7457).
• 61.9% LS mean reduction in EASI score from baseline, compared to 51.1% on placebo (p=0.1054).

Overall, discontinuation rates were comparable between the active treatment arms and higher in the placebo arm. No new safety signals were seen and the frequency of adverse events (AEs) was comparable between active treatment and placebo arms. The most frequently observed AEs across all active treatment arms were nasopharyngitis (13.4% compared to 8.8% for placebo), atopic dermatitis (8.6% compared to 7.0% for placebo), headache (6.9% compared to 7.0% for placebo) and upper respiratory tract infection (6.5% compared to 5.3% for placebo). Rates of conjunctivitis (5.2% compared to 1.8% for placebo), injection site reactions (4.7% compared to 1.8% for placebo) and herpes infections (3.0% compared to 3.5% for placebo) were low.

Further data from the Phase 2b study, including patient reported outcomes and biomarker data, is expected to be available in Q4 2023 and submitted for presentation at a future scientific congress. 

“We are delighted to announce these positive topline data from the TREK-AD study, which support recent translational studies we have published showing eblasakimab’s unique mechanism of action may provide a more efficient and targeted approach to blocking Type 2 signaling, which is responsible for allergic inflammation. Based on these results, we believe that eblasakimab could be a leading treatment in AD, if approved, getting more patients to EASI-75 or EASI-90, with fewer unwanted side effects, a rapid onset of action, and – uniquely – once-monthly dosing convenience,” adds Dr Carl Firth, Chief Executive Officer of ASLAN Pharmaceuticals. “We look forward to advancing quickly into a Phase 3 program in AD, and exploring the broad range of indications where we would expect this drug candidate to be successful. We are grateful to the patients, investigators, and our team who have made such an important contribution to the development of eblasakimab.”

Next Steps

ASLAN plans to meet with the US Food and Drug Administration for an end-of-Phase 2 meeting and expects to initiate a Phase 3 clinical development program for eblasakimab in 2024. The Company is also conducting the TREK-DX (TRials in EblasaKimab in Dupilumab eXperienced AD patients) study of eblasakimab in dupilumab-experienced patients and expects to announce topline data from that study in 1Q 2024.