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.
与之前使用生物制剂进行的特应性皮炎（AD）研究相比，22名患者的中期读数显示出前所未有的疗效数据：在每周接受400mg elasakimab治疗的dupilumab经验的AD患者中，有60.0％达到了 EASI-90（湿疹区域严重程度指数（EASI）评分至少降低了90％），66.7％在16周后获得0或1（透明或几乎透明的皮肤）的VigA分数，而服用安慰剂的患者为14.3％。
在接受依拉沙基单抗治疗的患者中，有20％达到了 EASI-100（EASI评分降低了100％），而使用安慰剂的患者为0％。
在接受依拉沙基单抗治疗的六名患者中，先前对杜匹鲁单抗反应不佳的患者中，66.7% 的患者在 16 周后达到 EASI-90，ViGa 评分为 0 或 1。
与安慰剂相比，Eblasakimab可以快速缓解瘙痒，具有临床意义。接受eblasakimab治疗的患者的瘙痒数字评级量表（PP-NRS）分数的平均下降幅度为58.9％，而安慰剂的平均下降幅度为12.9％。
这项针对有dupilumab经验的AD患者的独特研究的数据表明，即使没有使用dupilumab，依拉萨基单抗也有可能对AD患者产生高效的疗效。
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).
加利福尼亚州圣马特奥和新加坡，2024年4月22日（GLOBE NEWSWIRE）——亚斯兰制药（纳斯达克股票代码：ASLN）是一家临床阶段、专注于免疫学的生物制药公司，该公司正在开发创新疗法，以改变患者生活，今天宣布了依拉沙基单抗针对先前接受过双毛治疗的中度至重度特应性皮炎（AD）成年患者的2期研究的积极中期结果 mab，TREK-DX。主要终点是湿疹区域严重程度指数（EASI）分数从基线到第16周的变化百分比，与安慰剂（p=0.0059）相比，具有统计学意义，尽管由于样本量的原因，中期分析没有统计学意义。73.3％（11/15）接受依拉西单抗治疗的患者的EASI评分比基线（EASI-75）的14.3％降低了至少75％（）(1/7) 使用安慰剂（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.
“我们非常高兴看到eblasakimab使用比我们之前测试的更高的给药方案提供这些惊人的结果。大多数服用依拉萨基单抗的患者在短短16周的治疗后就达到了 0 或 1 的 EASI-90 和 vIgA，这一数字在其他生物制剂 AD 研究中是前所未有的。值得注意的是，在以前对dupilumab反应不足的患者中，三分之二的患者在接受依布拉萨基单抗治疗时达到 EASI-90 和ViGA 0或1。” ASLAN Pharmicals首席执行官卡尔·菲斯博士说。
"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."
“我们知道，超过60％的接受dupilumab治疗的患者在16周后未能达到0或1的IGA分数1，而且，在达到该分数的患者中，仍有一半在随后的36周后没有保持IGA分数2。我们今天公布的数据提供了令人信服的证据，表明依布拉萨基单抗凭借其独特的作用机制，有可能成为这一新兴患者群体的重要新疗法。我们期待在今年年底公布TREK-DX研究完整数据集的头条结果，这是第一项也是唯一一项针对有dupilumab经验的AD患者的安慰剂对照研究，并对计划中的依拉萨基单抗的3期研究中患者的剂量方案进行优化。”
Summary of the interim data
临时数据摘要
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试验正在招收中度至重度成人AD患者，这些患者在dupilumab治疗至少16周后因任何原因停止了dupilumab治疗，包括AD控制不足、无法获得治疗或不良事件。在对22名患者数据的中期分析中，包括意向治疗（ITT）人群，这些患者以 2:1 的活性随机分配给安慰剂，17名患者完成了16周的治疗期，5名患者（两名在活动组，三名在安慰剂组）在16周的治疗期结束前停药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:
每周一次接受依拉萨基单抗400mg（n = 15）治疗的患者在治疗的前几周迅速开始起作用，与安慰剂（n=7）相比，第4周的EASI评分（p=0.0169）有统计学上的显著改善。到第16周，观察到接受依拉西单抗治疗的患者的EASI分数比基线平均下降了86.9％4，而安慰剂的平均EASI分数下降了51.2％（p=0.0059）。与安慰剂相比，其他关键疗效指标在第16周取得了具有临床意义的改善，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).
在接受依拉西单抗治疗的患者中，有73.3％（11/15）获得了 EASI-75，而使用安慰剂的患者中有 14.3%（1/7）获得了（p = 0.0431）。
在接受依拉西单抗治疗的患者中，有60.0％（9/15）获得了 EASI-90，而使用安慰剂的患者中有 14.3%（1/7）（p = 0.1278）。
在接受依拉西单抗治疗的患者中，有20.0％（3/15）获得了 EASI-100，而使用安慰剂的患者中为0％（0/7）（EASI-100 不是预先规定的终点）。
在接受依拉西单抗治疗的患者中，有66.7％（10/15）的VigA分数为0或1，而使用安慰剂的患者获得的ViGa分数为14.3％（1/7）（p = 0.0750）。
接受依拉西单抗治疗的患者的瘙痒数值评分量表（PP-NRS）的平均降幅为58.9％，而安慰剂的平均降幅为12.9％（p=0.0015）。在接受依拉麻单抗治疗的患者中，53.8％（7/13）的PP-NRS评分下降了4个百分点，而安慰剂的评分为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.
在接受依拉沙基单抗治疗的六名患者中，先前对杜匹鲁单抗反应不佳的患者中，66.7％（4/6）获得了 EASI-90，66.7％（4/6）的VigA分数为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.
治疗耐受性良好，未发现新的安全信号。活性组或安慰剂组没有结膜炎或注射部位反应的报道。
Summary of data from subgroup with baseline EASI score of 18 or above
来自基线 EASI 分数为 18 或以上的子组的数据摘要
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:
正如先前宣布的那样，TREK-DX的招募标准已于2023年10月收紧，仅招收基线EASI分数为18或以上的患者。这些更严格的标准将成为预计于2024年底发布的头条新闻的分析基础。在本中期分析的22名患者中，有15名符合这些修订后的入组标准，并且在第16周得出以下疗效发现：
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).
接受依拉西单抗治疗的患者的EASI评分平均比基线下降89.2％，而安慰剂的平均降幅为45.7％（p=0.0045）。
在接受依拉西单抗治疗的患者中，有83.3％（10/12）获得了 EASI-75，而使用安慰剂的患者中为0％（0/3）（p = 0.0556）。
在接受依拉西单抗治疗的患者中，有66.7％（8/12）获得了 EASI-90，而使用安慰剂的患者中为0％（0/3）（p = 0.1667）。
25％（3/12）接受依拉西单抗治疗的患者获得了 EASI-100，而使用安慰剂的患者中有 0%（0/3）（EASI-100 不是预先规定的终点）。
在接受依拉西单抗治疗的患者中，有75.0％（9/12）的ViGa分数为0或1，而使用安慰剂的患者为0％（0/3）（p = 0.1111）。
接受依拉西单抗治疗的患者的PP-NRS评分平均下降了61.2％，而安慰剂的PP-NRS评分平均下降了1.5％（p=0.0004）。在接受依拉西单抗治疗的患者中，60％（6/10）的PP-NRS评分下降了4个百分点，而安慰剂的评分为0％（0/3）（p = 0.2000）。
The interim data will be submitted for presentation at an upcoming scientific conference.
临时数据将提交给即将举行的科学会议。