ASLAN Pharmaceuticals Announces Positive Interim Results From Phase 2 Study of Eblasakimab in Dupilumab-Experienced Atopic Dermatitis Patients
ASLAN Pharmaceuticals Announces Positive Interim Results From Phase 2 Study of Eblasakimab in Dupilumab-Experienced Atopic Dermatitis Patients
Interim readout of 22 patients shows unprecedented efficacy data compared to prior atopic dermatitis (AD) studies with biologics: 60.0% of dupilumab-experienced AD patients treated with 400mg eblasakimab weekly achieved EASI-90 (at least a 90% reduction in their Eczema Area Severity Index (EASI) score) and 66.7% achieved a vIGA score of 0 or 1 (clear or almost clear skin) after 16 weeks, versus 14.3% of patients on placebo.
20% of patients treated with eblasakimab achieved EASI-100 (100% reduction in their EASI score) versus 0% on placebo.
Of the six patients treated with eblasakimab that previously had an inadequate response to dupilumab, 66.7% achieved EASI-90 and a vIGA score of 0 or 1 after 16 weeks.
Eblasakimab produced rapid and clinically meaningful itch relief versus placebo. The mean reduction in peak pruritus numerical rating scale (PP-NRS) score for eblasakimab-treated patients was 58.9% compared to a 12.9% reduction for placebo.
Data from this unique study of dupilumab-experienced AD patients shows eblasakimab has the potential to be highly effective in AD patients even if dupilumab has not been.
與之前使用生物製劑進行的特應性皮炎（AD）研究相比，22名患者的中期讀數顯示出前所未有的療效數據：在每週接受400mg elasakimab治療的dupilumab經驗的AD患者中，有60.0％達到了 EASI-90（溼疹區域嚴重程度指數（EASI）評分至少降低了90％），66.7％在16周後獲得0或1（透明或幾乎透明的皮膚）的VigA分數，而服用安慰劑的患者爲14.3％。
在接受依拉沙基單抗治療的患者中，有20％達到了 EASI-100（EASI評分降低了100％），而使用安慰劑的患者爲0％。
在接受依拉沙基單抗治療的六名患者中，先前對杜匹魯單抗反應不佳的患者中，66.7% 的患者在 16 周後達到 EASI-90，ViGa 評分爲 0 或 1。
與安慰劑相比，Eblasakimab可以快速緩解瘙癢，具有臨床意義。接受eblasakimab治療的患者的瘙癢數字評級量表（PP-NRS）分數的平均下降幅度爲58.9％，而安慰劑的平均下降幅度爲12.9％。
這項針對有dupilumab經驗的AD患者的獨特研究的數據表明，即使沒有使用dupilumab，依拉薩基單抗也有可能對AD患者產生高效的療效。
SAN MATEO, Calif. and SINGAPORE, April 22, 2024 (GLOBE NEWSWIRE) -- ASLAN Pharmaceuticals (Nasdaq: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, today announced positive interim results from the Phase 2 study of eblasakimab in moderate-to-severe atopic dermatitis (AD) adult patients previously treated with dupilumab, TREK-DX. The primary endpoint, which is the percent change in Eczema Area Severity Index (EASI) score from baseline to week 16, was statistically significant when compared to placebo (p=0.0059), even though the interim analysis was not powered for statistical significance due to the sample size. 73.3% (11/15) of eblasakimab-treated patients achieved a reduction in EASI score of at least 75% from baseline (EASI-75) compared to 14.3% (1/7) on placebo (p=0.0431).
加利福尼亞州聖馬特奧和新加坡，2024年4月22日（GLOBE NEWSWIRE）——亞斯蘭製藥（納斯達克股票代碼：ASLN）是一家臨床階段、專注於免疫學的生物製藥公司，該公司正在開發創新療法，以改變患者生活，今天宣佈了依拉沙基單抗針對先前接受過雙毛治療的中度至重度特應性皮炎（AD）成年患者的2期研究的積極中期結果 mab，TREK-DX。主要終點是溼疹區域嚴重程度指數（EASI）分數從基線到第16周的變化百分比，與安慰劑（p=0.0059）相比，具有統計學意義，儘管由於樣本量的原因，中期分析沒有統計學意義。73.3％（11/15）接受依拉西單抗治療的患者的EASI評分比基線（EASI-75）的14.3％降低了至少75％（）(1/7) 使用安慰劑（p=0.0431）。
"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 Dr Carl Firth, Chief Executive Officer of ASLAN Pharmaceuticals.
“我們非常高興看到eblasakimab使用比我們之前測試的更高的給藥方案提供這些驚人的結果。大多數服用依拉薩基單抗的患者在短短16周的治療後就達到了 0 或 1 的 EASI-90 和 vIgA，這一數字在其他生物製劑 AD 研究中是前所未有的。值得注意的是，在以前對dupilumab反應不足的患者中，三分之二的患者在接受依布拉薩基單抗治療時達到 EASI-90 和ViGA 0或1。” ASLAN Pharmicals首席執行官卡爾·菲斯博士說。
"We know that over 60% of dupilumab-treated patients fail to achieve an IGA score of 0 or 1 after 16 weeks1, and, of those patients that do achieve it, still half do not maintain it after the subsequent 36 weeks2. The data we have announced today provide compelling evidence that eblasakimab, with its unique mechanism of action, has the potential to be an important new therapy for this emerging patient population. We look forward to announcing the topline readout from the full dataset of the TREK-DX study at the end of this year, the first and only placebo-controlled study of dupilumab-experienced AD patients, and to optimizing the dose regimen for patients in the planned Phase 3 studies of eblasakimab."
“我們知道，超過60％的接受dupilumab治療的患者在16周後未能達到0或1的IGA分數1，而且，在達到該分數的患者中，仍有一半在隨後的36周後沒有保持IGA分數2。我們今天公佈的數據提供了令人信服的證據，表明依布拉薩基單抗憑藉其獨特的作用機制，有可能成爲這一新興患者群體的重要新療法。我們期待在今年年底公佈TREK-DX研究完整數據集的頭條結果，這是第一項也是唯一一項針對有dupilumab經驗的AD患者的安慰劑對照研究，並對計劃中的依拉薩基單抗的3期研究中患者的劑量方案進行優化。”
Summary of the interim data
臨時數據摘要
The TREK-DX trial is enrolling moderate-to-severe adult AD patients who have discontinued dupilumab treatment for any reason, including inadequate control of AD, loss of access or an adverse event, after at least 16 weeks of dupilumab treatment. In an interim analysis of data from 22 patients, comprising the intent-to-treat (ITT) population, that were randomized 2:1 active to placebo, 17 patients completed the 16-week treatment period and five patients (two in the active arm and three in the placebo arm) discontinued before the completion of the 16-week treatment period3.
TREK-DX試驗正在招收中度至重度成人AD患者，這些患者在dupilumab治療至少16周後因任何原因停止了dupilumab治療，包括AD控制不足、無法獲得治療或不良事件。在對22名患者數據的中期分析中，包括意向治療（ITT）人群，這些患者以 2:1 的活性隨機分配給安慰劑，17名患者完成了16周的治療期，5名患者（兩名在活動組，三名在安慰劑組）在16周的治療期結束前停藥3。
Patients treated with eblasakimab 400mg once weekly (n=15) saw a rapid onset of action in the first few weeks of treatment, with a statistically significant improvement in EASI score by Week 4 (p=0.0169) compared to placebo (n=7). By Week 16, a 86.9% mean reduction4 in EASI score from baseline was observed for eblasakimab-treated patients compared to a 51.2% reduction for placebo (p=0.0059). Clinically meaningful improvements were achieved in other key efficacy measures compared to placebo at Week 16, including:
每週一次接受依拉薩基單抗400mg（n = 15）治療的患者在治療的前幾周迅速開始起作用，與安慰劑（n=7）相比，第4周的EASI評分（p=0.0169）有統計學上的顯著改善。到第16周，觀察到接受依拉西單抗治療的患者的EASI分數比基線平均下降了86.9％4，而安慰劑的平均EASI分數下降了51.2％（p=0.0059）。與安慰劑相比，其他關鍵療效指標在第16周取得了具有臨床意義的改善，包括：
73.3% (11/15) of eblasakimab-treated patients achieved EASI-75, versus 14.3% (1/7) on placebo (p=0.0431).
60.0% (9/15) of eblasakimab-treated patients achieved EASI-90, versus 14.3% (1/7) on placebo (p=0.1278).
20.0% (3/15) of eblasakimab-treated patients achieved EASI-100, versus 0% (0/7) on placebo (EASI-100 was not a pre-specified endpoint).
66.7% (10/15) of eblasakimab-treated patients achieved a vIGA score of 0 or 1, versus 14.3% (1/7) with placebo (p=0.0750).
58.9% mean reduction in peak pruritus numerical rating scale (PP-NRS) score for eblasakimab-treated patients, versus a 12.9% reduction for placebo (p=0.0015). 53.8% (7/13) of eblasakimab-treated patients, with a baseline score of at least 4, achieved a 4-point reduction in PP-NRS score, versus 14.3% (1/7) on placebo (p=0.2460).
在接受依拉西單抗治療的患者中，有73.3％（11/15）獲得了 EASI-75，而使用安慰劑的患者中有 14.3%（1/7）獲得了（p = 0.0431）。
在接受依拉西單抗治療的患者中，有60.0％（9/15）獲得了 EASI-90，而使用安慰劑的患者中有 14.3%（1/7）（p = 0.1278）。
在接受依拉西單抗治療的患者中，有20.0％（3/15）獲得了 EASI-100，而使用安慰劑的患者中爲0％（0/7）（EASI-100 不是預先規定的終點）。
在接受依拉西單抗治療的患者中，有66.7％（10/15）的VigA分數爲0或1，而使用安慰劑的患者獲得的ViGa分數爲14.3％（1/7）（p = 0.0750）。
接受依拉西單抗治療的患者的瘙癢數值評分量表（PP-NRS）的平均降幅爲58.9％，而安慰劑的平均降幅爲12.9％（p=0.0015）。在接受依拉麻單抗治療的患者中，53.8％（7/13）的PP-NRS評分下降了4個百分點，而安慰劑的評分爲14.3％（1/7）（p=7）0.2460)。
Of the six 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.
在接受依拉沙基單抗治療的六名患者中，先前對杜匹魯單抗反應不佳的患者中，66.7％（4/6）獲得了 EASI-90，66.7％（4/6）的VigA分數爲0或1。
Treatment was well-tolerated and no new safety signals were identified. There were no reports of conjunctivitis or injection site reactions in the active or placebo arm.
治療耐受性良好，未發現新的安全信號。活性組或安慰劑組沒有結膜炎或注射部位反應的報道。
Summary of data from subgroup with baseline EASI score of 18 or above
來自基線 EASI 分數爲 18 或以上的子組的數據摘要
As previously announced, the TREK-DX recruitment criteria were tightened in October 2023 to enroll only patients with a baseline EASI score of 18 or above. These more stringent criteria will be the basis of analysis in the topline readout, expected at the end of 2024. Of the 22 patients in this interim analysis, 15 meet these amended enrollment criteria, and have the following efficacy findings at Week 16:
正如先前宣佈的那樣，TREK-DX的招募標準已於2023年10月收緊，僅招收基線EASI分數爲18或以上的患者。這些更嚴格的標準將成爲預計於2024年底發佈的頭條新聞的分析基礎。在本中期分析的22名患者中，有15名符合這些修訂後的入組標準，並且在第16周得出以下療效發現：
89.2% mean reduction in EASI score from baseline for eblasakimab-treated patients, versus a 45.7% reduction for placebo (p=0.0045).
83.3% (10/12) of eblasakimab-treated patients achieved EASI-75, versus 0% (0/3) on placebo (p=0.0556).
66.7% (8/12) of eblasakimab-treated patients achieved EASI-90, versus 0% (0/3) on placebo (p=0.1667).
25% (3/12) of eblasakimab-treated patients achieved EASI-100, versus 0% (0/3) on placebo (EASI-100 was not a pre-specified endpoint).
75.0% (9/12) of eblasakimab-treated patients achieved a vIGA score of 0 or 1, versus 0% (0/3) with placebo (p=0.1111).
61.2% mean reduction in PP-NRS score for eblasakimab-treated patients, versus a 1.5% increase for placebo (p=0.0004). 60% (6/10) of eblasakimab-treated patients, with a baseline score of least 4, achieved a 4-point reduction in PP-NRS score, versus 0% (0/3) on placebo (p=0.2000).
接受依拉西單抗治療的患者的EASI評分平均比基線下降89.2％，而安慰劑的平均降幅爲45.7％（p=0.0045）。
在接受依拉西單抗治療的患者中，有83.3％（10/12）獲得了 EASI-75，而使用安慰劑的患者中爲0％（0/3）（p = 0.0556）。
在接受依拉西單抗治療的患者中，有66.7％（8/12）獲得了 EASI-90，而使用安慰劑的患者中爲0％（0/3）（p = 0.1667）。
25％（3/12）接受依拉西單抗治療的患者獲得了 EASI-100，而使用安慰劑的患者中有 0%（0/3）（EASI-100 不是預先規定的終點）。
在接受依拉西單抗治療的患者中，有75.0％（9/12）的ViGa分數爲0或1，而使用安慰劑的患者爲0％（0/3）（p = 0.1111）。
接受依拉西單抗治療的患者的PP-NRS評分平均下降了61.2％，而安慰劑的PP-NRS評分平均下降了1.5％（p=0.0004）。在接受依拉西單抗治療的患者中，60％（6/10）的PP-NRS評分下降了4個百分點，而安慰劑的評分爲0％（0/3）（p = 0.2000）。
The interim data will be submitted for presentation at an upcoming scientific conference.
臨時數據將提交給即將舉行的科學會議。