Download PDF

下载PDF

ACCORD-2 Phase 3 trial in Alzheimer’s disease agitation achieves primary endpoint compared to placebo (p=0.001, time to relapse)

ACCORD-2 Phase 3 trial achieves key secondary endpoint compared to placebo (p=0.001, prevention of relapse of Alzheimer’s disease agitation)

与安慰剂相比，ACCORD-2 3期试验达到了关键的次要终点（p=0.001，预防阿尔茨海默病复发）

AXS-05 reduced worsening of Alzheimer’s disease overall compared to placebo in ACCORD-2 Phase 3 trial (p<0.001, CGI-S Alzheimer’s disease overall clinical status)

在ACCORD-2 3期试验中，与安慰剂相比，AXS-05总体上减少了阿尔茨海默病的恶化（p<0.001，CGI-s阿尔茨海默病总体临床状况）

ADVANCE-2 trial did not demonstrate statistical significance on primary endpoint; numerically greater improvements with AXS-05 over placebo (primary and secondary endpoints)

ADVANCE-2试验未显示主要终点的统计学意义；与安慰剂相比，AXS-05在数值上有更大的改进（主要和次要终点）

Long-term safety trial completed with required number of patients treated for 6 and 12 months

长期安全性试验已完成，需要治疗6个月和12个月的患者数量

AXS-05 was well tolerated in controlled and long-term trials, and was not associated with death, increased risk of falls, cognitive decline, or sedation

AXS-05在对照和长期试验中耐受性良好，与死亡、跌倒风险增加、认知能力下降或镇静无关

Four completed pivotal, Phase 3, placebo-controlled trials support efficacy and safety of AXS-05 in Alzheimer’s disease agitation

四项完成的关键性3期安慰剂对照试验支持AXS-05在阿尔茨海默病激越中的疗效和安全性

The Company plans to submit a New Drug Application (NDA) to the FDA in 2H 2025

该公司计划在2025年下半年向FDA提交新药申请（NDA）

Conference call and webcast to take place today at 8:00 AM Eastern

电话会议和网络广播将于今天上午8:00东部时间举行

NEW YORK, Dec. 30, 2024 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced the successful completion of its Phase 3 clinical program evaluating AXS-05 (dextromethorphan-bupropion), a novel, oral, investigational NMDA receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor, in Alzheimer’s disease agitation, and results of the ACCORD-2, ADVANCE-2, and long-term safety trials in this indication..

2024年12月30日，纽约（环球通讯社）--Axsome Therapeutics，Inc.（纳斯达克：AXSM），一家开发和提供中枢神经系统（CNS）疾病治疗新疗法的生物制药公司，今天宣布成功完成其第三阶段临床计划，评估新型口服研究性NMDA受体拮抗剂sigma-1激动剂和氨基酮CYP2D6抑制剂AXS-05（右美沙芬安非他酮）在阿尔茨海默病激越中的作用，以及ACCORD-2，ADVANCE-2和该适应症的长期安全性试验结果。。

The ACCORD-2 Phase 3 trial achieved the primary endpoint with AXS-05 statistically significantly delaying the time to relapse of agitation, assessed by the Cohen-Mansfield Agitation Inventory (CMAI) total score, in patients with Alzheimer’s disease compared to placebo (hazard ratio for time to relapse of 0.276, p=0.001), demonstrating a 3.6-fold lower risk of relapse compared to placebo.

ACCORD-2 3期临床试验达到了主要终点，AXS-05在统计学上显着延迟了阿尔茨海默病患者与安慰剂相比，Cohen-Mansfield躁动量表（CMAI）总分评估的躁动复发时间（复发时间风险比为0.276，p=0.001），表明复发风险比安慰剂低3.6倍。

AXS-05 also met the key secondary endpoint (relapse prevention, p=0.001). Further, AXS-05 reduced worsening for overall Alzheimer’s disease severity compared to placebo, as assessed by the Clinical Global Impression of Severity (CGI-S) for Alzheimer’s disease (p<0.001)..

AXS-05也达到了关键的次要终点（预防复发，p=0.001）。此外，根据阿尔茨海默病临床总体严重程度印象（CGI-s）评估，与安慰剂相比，AXS-05降低了阿尔茨海默病总体严重程度的恶化（p＜0.001）。。

The ADVANCE-2 Phase 3 trial did not demonstrate statistical significance for the primary endpoint, change in the CMAI total score from baseline to Week 5 (CMAI reductions of 13.8 and 12.6 points for AXS-05 and placebo, respectively). However, results for the primary and nearly all secondary endpoints numerically favored AXS-05 over placebo..

ADVANCE-2 3期试验未显示主要终点的统计学显着性，即CMAI总分从基线到第5周的变化（AXS-05和安慰剂的CMAI分别降低13.8和12.6分）。然而，主要终点和几乎所有次要终点的结果在数值上都优于安慰剂。。

AXS-05 was safe and well tolerated in both controlled studies. The long-term safety and tolerability of AXS-05 was also evaluated in more than 300 subjects treated for at least 6 months and more than 100 subjects treated for at least 12 months. In the controlled and long-term studies in subjects with Alzheimer’s disease, AXS-05 was not associated with increased risk of falls, cognitive decline, or sedation.

在两项对照研究中，AXS-05均安全且耐受性良好。AXS-05的长期安全性和耐受性也在300多名接受至少6个月治疗的受试者和100多名接受至少12个月治疗的受试者中进行了评估。。

In the clinical program for AXS-05 in Alzheimer’s disease agitation, there have been no deaths in subjects receiving AXS-05..

在阿尔茨海默病激越的AXS-05临床计划中，接受AXS-05的受试者没有死亡。。

AXS-05 has now demonstrated statistically significant efficacy compared to placebo in three completed pivotal Phase 3 trials (ADVANCE-1, ACCORD-1 and ACCORD-2), with supportive efficacy and controlled safety results in a fourth trial (ADVANCE-2). Axsome plans to submit an NDA for AXS-05 in Alzheimer’s disease agitation to the FDA in the second half of 2025, based on the efficacy and safety data from the above controlled and long-term studies.

与安慰剂相比，AXS-05在三项完成的关键性3期试验（ADVANCE-1，ACCORD-1和ACCORD-2）中显示出统计学上显着的疗效，在第四项试验（ADVANCE-2）中具有支持疗效和受控安全性结果。Axsome计划根据上述对照和长期研究的有效性和安全性数据，于2025年下半年向FDA提交关于阿尔茨海默病激动中AXS-05的NDA。

AXS-05 has been granted Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation..

AXS-05已被授予治疗阿尔茨海默病激动症的突破性治疗称号。。

Jeffrey Cummings, MD, ScD, Vice Chair of Research, UNLV Department of Brain Health commented, 'Agitation is one of the most troubling and consequential aspects of Alzheimer’s disease, poses significant challenges to both the patient and their family, and represents a high unmet need. The robust, clinically meaningful efficacy results of the ACCORD-2 trial are consistent with the statistically significant results of the previously completed ADVANCE-1 and ACCORD-1 Phase 3 trials of AXS-05.

UNLV脑健康部研究副主席、医学博士、ScD杰弗里·卡明斯（JeffreyCummings）评论道：“激动是阿尔茨海默病最令人不安和最重要的方面之一，对患者及其家人都构成了重大挑战，并且代表着高度未满足的需求。ACCORD-2试验的稳健，临床上有意义的疗效结果与先前完成的AXS-05 ADVANCE-1和ACCORD-1 3期试验的统计学显着结果一致。

The improvement in overall Alzheimer's disease severity with AXS-05 in the ACCORD-2 trial is noteworthy. Importantly, short and long-term treatment with AXS-05 was well tolerated and not associated with increased mortality, risk of falls, sedation, or cognitive decline. Taken together, results from this comprehensive Phase 3 program encompassing distinct clinical trial designs strongly support the potential for AXS-05 to become an important treatment for patients living with Alzheimer’s disease agitation.'.

在ACCORD-2试验中，AXS-05对阿尔茨海默氏病总体严重程度的改善值得注意。重要的是，AXS-05的短期和长期治疗耐受性良好，与死亡率增加，跌倒风险，镇静或认知能力下降无关。综上所述，这项涵盖不同临床试验设计的综合性3期计划的结果强烈支持AXS-05成为阿尔茨海默病激越患者的重要治疗方法。”。

Herriot Tabuteau, MD, CEO of Axsome Therapeutics, added, “We are very pleased with the successful completion of the planned Phase 3 clinical trial program of AXS-05 in the treatment of Alzheimer’s disease agitation. With the strong results of the ACCORD-2 trial, AXS-05 has now demonstrated substantial and statistically significant improvements in Alzheimer’s disease agitation across three pivotal, Phase 3, placebo-controlled trials, underscoring its potential to provide meaningful benefit to patients living with this condition and their families.

Axsome Therapeutics首席执行官Herriot Tabuteau医学博士补充道：“我们非常高兴计划中的AXS-05治疗阿尔茨海默氏病躁动的3期临床试验项目成功完成。随着ACCORD-2试验的强劲结果，AXS-05现在在三项关键的3期安慰剂对照试验中显示出阿尔茨海默氏病躁动的显着和统计学显着改善，强调了其为患有这种疾病的患者及其家人提供有意义益处的潜力。

The improvements in the AXS-05 arm relative to placebo in ADVANCE-2 did not reach statistical significance. However, we are pleased with the very positive controlled safety data from this trial which will be an essential part of our planned NDA submission of AXS-05 in Alzheimer’s disease agitation, which is targeted for the second half of 2025.”.

AXS-05组相对于安慰剂ADVANCE-2的改善没有达到统计学意义。然而，我们对这项试验的非常积极的控制安全性数据感到满意，这将是我们计划在2025年下半年提交的阿尔茨海默病激动症AXS-05 NDA的重要组成部分。”。

Summary of Topline Results of the ACCORD-2 Phase 3 Trial

ACCORD-2第三阶段试验的主要结果摘要

ACCORD-2 was a double-blind, placebo-controlled, randomized withdrawal trial of AXS-05 in Alzheimer’s disease patients with agitation, consisting of an open-label AXS-05 treatment period, and a randomized, double-blind treatment period. Patients who achieved a sustained clinical response with open-label AXS-05 were then randomized into the double-blind treatment period to either continue on AXS-05 or to switch to placebo..

ACCORD-2是一项双盲，安慰剂对照，随机撤回AXS-05治疗阿尔茨海默病躁动患者的试验，包括开放标签的AXS-05治疗期和随机双盲治疗期。然后，使用开放标签AXS-05获得持续临床反应的患者被随机分配到双盲治疗期，以继续使用AXS-05或改用安慰剂。。

Open-Label AXS-05 Treatment Period

开放标签AXS-05治疗期

A total of 295 patients were treated with open-label AXS-05 for up to 12 months and assessed for efficacy. The mean CMAI total score was 73.3 at baseline.

共有295名患者接受开放标签AXS-05治疗长达12个月，并评估疗效。基线时平均CMAI总分为73.3。

Treatment with AXS-05 was associated with a mean reduction from baseline in the CMAI total score of 20.4 points at Week 6, representing a 46% reduction from the mean baseline score.

AXS-05治疗与第6周CMAI总分从基线平均降低20.4分相关，比平均基线得分降低46%。

Clinical response on the CMAI (defined as ≥30% reduction from baseline) after treatment with AXS-05 was achieved by 69% of patients at Week 6, after treatment with AXS-05.

在用AXS-05治疗后，69%的患者在第6周达到了用AXS-05治疗后CMAI的临床反应（定义为比基线降低≥30%）。

Improvement in Alzheimer's disease agitation, assessed using the clinician rated modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC), was achieved by 78% of patients at Week 6, after treatment with AXS-05.

在用AXS-05治疗后的第6周，78%的患者在使用临床医生评定的改良阿尔茨海默氏病合作研究临床总体印象变化（mADCS-CGIC）评估的阿尔茨海默氏病激动的改善。

Improvement in Alzheimer's disease agitation, assessed using the caregiver rated Patient Global Impression of Change (PGI-C), was achieved by 71% of patients at Week 4, and 78% of patients at Week 8, after treatment with AXS-05.

在用AXS-05治疗后，71%的患者在第4周和78%的患者在第8周达到了使用护理人员评定的患者整体变化印象（PGI-C）评估的阿尔茨海默病激动的改善。

Of the patients treated for at least 8 weeks, 70% experienced a sustained clinical response and were randomized in the double-blind period.

在接受至少8周治疗的患者中，70%经历了持续的临床反应，并在双盲期随机分组。

Double-Blind Randomized Period

双盲随机周期

A total of 167 patients were randomized, 83 to continued treatment with AXS-05, and 84 switched to placebo. The mean CMAI total scores at randomization were 44.3 and 45.4 for the AXS-05 and placebo groups respectively.

共有167名患者被随机分组，83名患者继续接受AXS-05治疗，84名患者改用安慰剂。AXS-05组和安慰剂组的随机平均CMAI总分分别为44.3和45.4。

AXS-05 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of Alzheimer’s disease agitation as compared to placebo (hazard ratio for time to relapse of 0.276, p=0.001), demonstrating a 3.6-fold lower risk of relapse compared to placebo.

与安慰剂相比，AXS-05通过显着且统计学上显着延迟阿尔茨海默病激动的复发时间达到了主要终点（复发时间的风险比为0.276，p=0.001），表明复发风险比安慰剂低3.6倍。

AXS-05 met the key secondary endpoint by substantially and statistically significantly preventing relapse of Alzheimer's disease agitation as compared to placebo, with 8.4% of AXS-05 patients relapsing versus 28.6% of patients switched to placebo (p=0.001).

与安慰剂相比，AXS-05通过显着且统计学显着地预防阿尔茨海默病激动的复发而达到了关键的次要终点，其中8.4%的AXS-05患者复发，而28.6%的患者改用安慰剂（p=0.001）。

AXS-05 substantially and statistically significantly prevented worsening of severity of Alzheimer's disease agitation as compared to placebo, with 20.5% of AXS-05 patients worsening on the CGI-S for agitation versus 41.7% of patients switched to placebo (p=0.004).

与安慰剂相比，AXS-05显着且统计学显着地防止了阿尔茨海默病激越严重程度的恶化，其中20.5%的AXS-05患者在CGI-s上激越恶化，而41.7%的患者改用安慰剂（p=0.004）。

AXS-05 substantially and statistically significantly prevented worsening of severity of Alzheimer's disease overall as compared to placebo, with 13.3% of AXS-05 patients worsening on the CGI-S for Alzheimer’s disease overall clinical status versus 39.3% of patients switched to placebo (p<0.001).

与安慰剂相比，AXS-05显着且统计学上显着地防止了阿尔茨海默病严重程度的恶化，13.3%的AXS-05患者在CGI-s上阿尔茨海默病总体临床状况恶化，而39.3%的患者改用安慰剂（p<0.001）。

The overall rates of adverse events in the double-blind period were 29.3% in the AXS-05 group and 32.1% in the placebo group, with no individual adverse events occurring in more than 3.7% of subjects. Two subjects (2.4%) in the AXS-05 group experienced falls, only one which was deemed related to study medication.

双盲期不良事件的总体发生率在AXS-05组为29.3%，安慰剂组为32.1%，超过3.7%的受试者未发生个体不良事件。AXS-05组中有两名受试者（2.4%）跌倒，只有一名被认为与研究药物有关。

There were two serious adverse events in the double-blind period (cellulitis and urinary retention) both of which occurred in the placebo group. Discontinuations in the double-blind period due to adverse events were low (0% for AXS-05 and 1.2% for placebo)..

在双盲期有两个严重的不良事件（蜂窝织炎和尿潴留），这两个都发生在安慰剂组。由于不良事件导致的双盲期中断率很低（AXS-05为0%，安慰剂为1.2%）。。

There were no deaths in the ACCORD-2 trial, and AXS-05 was not associated with sedation or cognitive decline as assessed by the Mini-Mental State Examination (MMSE).

ACCORD-2试验中没有死亡，根据简易精神状态检查（MMSE）评估，AXS-05与镇静或认知能力下降无关。

Summary of Topline Results of the ADVANCE-2 Phase 3 Trial

ADVANCE-2第三阶段试验的主要结果摘要

The ADVANCE-2 trial was a double-blind, placebo-controlled, parallel group trial of AXS-05 in Alzheimer’s disease patients with agitation. A total of 408 patients were randomized in a 1:1 ratio to treatment with AXS-05 or placebo, for 5 weeks.

ADVANCE-2试验是一项针对阿尔茨海默病躁动患者的AXS-05双盲，安慰剂对照，平行组试验。。

The study did not demonstrate statistical significance for the primary endpoint, change in the CMAI total score from baseline to Week 5 (CMAI reductions of 13.8 and 12.6 points for AXS-05 and placebo, respectively).

该研究没有显示主要终点的统计学显着性，即CMAI总分从基线到第5周的变化（AXS-05和安慰剂的CMAI分别降低13.8和12.6分）。

Results of the primary endpoint and almost all secondary endpoints numerically favored AXS-05 over the placebo group.

主要终点和几乎所有次要终点的结果在数值上优于安慰剂组的AXS-05。

The overall rates of adverse event in ADVANCE-2 were 26.0% in the AXS-05 group and 21.6% in the placebo group. The most common adverse events were dizziness (5.9% for AXS-05 and 1.5% for placebo), and headache (4.4% for AXS-05 and 3.4% placebo). One subject (0.5%) each in the AXS-05 and placebo groups experienced falls, which was deemed not related to study medication for the subject in the AXS-05 group.

AXS-05组不良事件发生率为26.0%，安慰剂组为21.6%。最常见的不良事件是头晕（AXS-05为5.9%，安慰剂为1.5%）和头痛（AXS-05为4.4%，安慰剂为3.4%）。AXS-05组和安慰剂组各有一名受试者（0.5%）跌倒，这被认为与AXS-05组受试者的研究药物无关。

Two subjects in the AXS-05 group reported three serious adverse events, none of which were deemed related to study drug (asthenia, urinary tract infection, cerebrovascular accident). Discontinuation due to adverse events were low (1.5% for AXS-05 and 0% for placebo)..

AXS-05组的两名受试者报告了三次严重不良事件，其中没有一次被认为与研究药物有关（虚弱，尿路感染，脑血管意外）。不良事件导致的停药率较低（AXS-05为1.5%，安慰剂为0%）。。

In the ADVANCE-2 trial, there were no deaths and AXS-05 was not associated with sedation or cognitive decline as assessed by the MMSE.

在ADVANCE-2试验中，没有死亡，并且根据MMSE评估，AXS-05与镇静或认知能力下降无关。

Summary of Long-Term Safety

长期安全总结

A total of 456 subjects were treated for up to 12 months with AXS-05 in the long-term open-label safety trial. AXS-05 was well tolerated with long-term dosing, with a safety profile consistent with the short-term efficacy and safety trials and no new safety signals identified.

在长期开放标签安全性试验中，共有456名受试者接受了长达12个月的AXS-05治疗。。

The overall rate of adverse events during the up to 12-month treatment period was 39.9%, with headache (5.5%) being the only adverse event occurring in ≥5% of subjects. The rate of falls over the up to 12-month treatment period was 3.1%, with only 0.2% deemed related to study medication. The rate of serious adverse events during the up to 12-month treatment period was 2.6%, none of which were deemed related to study drug.

在长达12个月的治疗期间，不良事件的总发生率为39.9%，≥5%的受试者发生头痛（5.5%）是唯一的不良事件。在长达12个月的治疗期间，跌倒率为3.1%，只有0.2%被认为与研究药物有关。在长达12个月的治疗期间，严重不良事件的发生率为2.6%，其中没有一个被认为与研究药物有关。

Discontinuations due to adverse events with long-term dosing were low (0.7%)..

长期服用不良事件导致的停药率较低（0.7%）。。

There were no deaths and AXS-05 was not associated with sedation or cognitive decline as assessed by the MMSE.

根据MMSE评估，没有死亡，AXS-05与镇静或认知能力下降无关。

Overall Phase 3 Clinical Development Program

总体3期临床开发计划

The comprehensive clinical development program of AXS-05 in Alzheimer’s disease agitation includes four completed pivotal, Phase 3, placebo-controlled trials that support the efficacy of AXS-05 in this indication:

AXS-05在阿尔茨海默病激越中的综合临床开发计划包括四项完成的关键性3期安慰剂对照试验，这些试验支持AXS-05在该适应症中的疗效：

ADVANCE-1 – achieved primary endpoint (p=0.010)

ADVANCE-1–达到主要终点（p=0.010）

ADVANCE-2 – primary endpoint not statistically significant

ADVANCE-2–主要终点无统计学意义

ACCORD-1 – achieved primary endpoint (p=0.014)

ACCORD-1–达到主要终点（p=0.014）

ACCORD-2 – achieved primary endpoint (p=0.001)

ACCORD-2–达到主要终点（p=0.001）

The long-term safety of AXS-05 in Alzheimer’s disease agitation has been demonstrated in over 300 patients treated for at least 6 months, and over 100 patients treated for at least 12 months.

AXS-05在阿尔茨海默病激越中的长期安全性已在300多名接受至少6个月治疗的患者和100多名接受至少12个月治疗的患者中得到证实。

Axsome plans to submit an NDA for AXS-05 in Alzheimer’s disease agitation to the FDA in the second half of 2025, based on the efficacy and safety data from these studies.

Axsome计划根据这些研究的有效性和安全性数据，于2025年下半年向FDA提交针对阿尔茨海默病激动症的AXS-05的NDA。

AXS-05 was granted Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020 based on positive results from the pivotal ADVANCE-1 trial. Breakthrough Therapy designation is granted to potentially expedite development and review timelines for a promising investigational medicine when preliminary clinical evidence indicates it may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for a serious or life-threatening condition..

根据关键的ADVANCE-1试验的积极结果，AXS-05于2020年6月被授予治疗阿尔茨海默病激动症的突破性治疗指定。当初步临床证据表明，对于严重或危及生命的疾病，突破性治疗指定可能会在一个或多个临床重要终点上显示出比现有治疗方法有实质性改善时，可能会加快有前途的研究药物的开发和审查时间表。。

Conference Call Information

电话会议信息

Axsome will host a conference call and webcast today at 8:00 a.m. Eastern Time to discuss the topline results of the ADVANCE-2 and ACCORD-2 Phase 3 trials of AXS-05 in Alzheimer’s disease agitation. Dr. Jeffrey Cummings, Vice Chair of Research, UNLV Department of Brain Health, will join the call and will be available to answer questions during the Q&A session.

Axsome将于东部时间今天上午8:00主持电话会议和网络广播，讨论AXS-05在阿尔茨海默病激越中的ADVANCE-2和ACCORD-2 3期试验的主要结果。UNLV大脑健康部研究副主席JeffreyCummings博士将加入呼叫，并在问答环节中回答问题。

To participate in the live conference call, please dial (877) 405-1239 (toll-free domestic) or +1 (201) 389-0851 (international). A live webcast of the conference call can be access on the “Webcasts & Presentations” page of the “Investors” section of the Company’s website at axsome.com. A replay of the conference call will be available for approximately 30 days following the live event..

要参加现场电话会议，请拨打（877）405-1239（国内免费电话）或+1（201）389-0851（国际）。可以在公司网站axsome.com的“投资者”部分的“网络广播和演示”页面上访问电话会议的现场网络广播。现场直播后约30天内将提供电话会议的重播。。

About the ADVANCE-2 Trial

关于ADVANCE-2试验

ADVANCE-2 (Addressing Dementia via Agitation-Centered Evaluation 2) was a Phase 3, randomized, double-blind, placebo-controlled, multicenter, 5-week parallel-group trial. The primary endpoint was the change from baseline in the CMAI total score at Week 5. The minimum score on the CMAI is 29, corresponding to the total absence of symptoms, with higher scores corresponding to greater agitation..

ADVANCE-2（通过以激动为中心的评估2解决痴呆症）是一项3期，随机，双盲，安慰剂对照，多中心，5周平行组试验。主要终点是第5周CMAI总分与基线的变化。CMAI的最低分数为29，对应于完全没有症状，分数越高对应于更大的激动。。

A total of 408 patients with a diagnosis of probable Alzheimer’s disease (AD) and clinically meaningful agitation associated with their AD were enrolled in the trial. Patients were randomized 1:1 to receive AXS-05 (dextromethorphan/bupropion, dose escalated from 30 mg/105 mg once daily to 45 mg/105 mg twice daily) or matching placebo for 5 weeks..

共有408名诊断为可能的阿尔茨海默病（AD）且与AD相关的临床意义激动的患者参加了该试验。患者以1:1的比例随机接受AXS-05（右美沙芬/安非他酮，剂量从每天一次30 mg/105 mg增加到每天两次45 mg/105 mg）或匹配的安慰剂治疗5周。。

About the ACCORD-2 Trial

关于ACCORD-2试验

ACCORD-2 (Assessing Clinical Outcomes in Alzheimer’s Disease Agitation 2) was a multicenter Phase 3 trial consisting of an open-label treatment period followed by a 26-week, double-blind, placebo-controlled, randomized withdrawal period. The primary endpoint was the time from randomization to relapse of AD agitation calculated by Kaplan-Meier estimates and the hazard ratio.

ACCORD-2（评估阿尔茨海默病激动2的临床结果）是一项多中心3期临床试验，包括开放标签治疗期，然后是26周，双盲，安慰剂对照，随机戒断期。。

The key secondary endpoint was the percentage of patients who relapsed compared to placebo..

关键的次要终点是与安慰剂相比复发患者的百分比。。

A total of 167 patients, who rolled over from the open-label extension trial of AXS-05, experienced a sustained clinical response with AXS-05 and were 1:1 randomized to continue AXS-05 (n=83) or to switch to placebo (n=84). Treatment was continued until either a relapse of agitation or the end of the 26-week double-blind period, whichever occurred first.

共有167名患者从AXS-05的开放标签扩展试验中翻身，经历了AXS-05的持续临床反应，并以1:1随机分配继续使用AXS-05（n=83）或改用安慰剂（n=84）。继续治疗直至激动复发或26周双盲期结束，以先发生者为准。

The mean CMAI total score at baseline study entry was 73.3. The mean CMAI total scores at randomization for the AXS-05 and placebo groups were 44.3 and 45.4, respectively..

基线研究入组时的平均CMAI总分为73.3。AXS-05组和安慰剂组的随机平均CMAI总分分别为44.3和45.4。。

About Alzheimer’s Disease Agitation

关于阿尔茨海默病激动

Alzheimer’s disease (AD) is the most common form of dementia, affecting approximately 7 million people in the United States.1 Agitation is reported in up to 70% of patients with AD and is characterized by emotional distress, verbal and physical aggressiveness, disruptive irritability, and disinhibition.1,2 AD agitation has been associated with accelerated cognitive decline, increased caregiver burden, earlier nursing home placement, and increased mortality.3.

阿尔茨海默病（AD）是痴呆症最常见的形式，影响美国约700万人[1]。据报道，高达70%的AD患者出现躁动，其特征是情绪困扰，言语和身体攻击性，破坏性易怒和去抑制[1,2]。AD躁动与认知能力下降加速，护理人员负担增加，早期疗养院安置和死亡率增加有关。

About AXS-05

关于AXS-05

AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor under development for the treatment of Alzheimer’s disease (AD) agitation and smoking cessation. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components.

AXS-05（右美沙芬安非他酮）是一种新型口服研究性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，sigma-1激动剂和氨基酮CYP2D6抑制剂，正在开发用于治疗阿尔茨海默病（AD）激动和戒烟。AXS-05利用专有配方和剂量的右美沙芬和安非他酮，以及Axsome的代谢抑制技术来调节成分的传递。

The dextromethorphan component of AXS-05 is an uncompetitive NMDA receptor antagonist, also known as a glutamate receptor modulator, and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan and is a norepinephrine and dopamine reuptake inhibitor.

AXS-05的右美沙芬成分是一种非竞争性NMDA受体拮抗剂，也称为谷氨酸受体调节剂和σ-1受体激动剂。AXS-05的安非他酮成分可提高右美沙芬的生物利用度，是去甲肾上腺素和多巴胺再摄取抑制剂。

AXS-05 is covered by a robust patent estate extending out to at least 2043. AXS-05 was granted U.S. FDA Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020..

。2020年6月，AXS-05被美国FDA授予治疗阿尔茨海默病激动症的突破性治疗称号。。

About Axsome Therapeutics

关于Axsome Therapeutics

Axsome Therapeutics is a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) conditions. We deliver scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes.

Axsome Therapeutics是一家生物制药公司，引领中枢神经系统（CNS）疾病治疗的新时代。我们通过确定护理中的关键差距来实现科学突破，并开发差异化产品，重点关注新的行动机制，从而在患者预后方面取得有意义的进步。

Our industry-leading neuroscience portfolio includes FDA-approved treatments for major depressive disorder and excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions that impact over 150 million people in the United States.

我们业界领先的神经科学产品组合包括FDA批准的与嗜睡症和阻塞性睡眠呼吸暂停相关的重度抑郁症和白天过度嗜睡的治疗方法，以及针对影响美国1.5亿多人的各种严重神经和精神疾病的多个晚期发展计划。

Together, we are on a mission to solve some of the brain’s biggest problems so patients and their loved ones can flourish. For more information, please visit the Company’s website at www.axsome.com..

我们共同致力于解决大脑的一些最大问题，使患者及其亲人能够茁壮成长。有关更多信息，请访问公司网站www.axsome.com。。

Forward Looking Statements

前瞻性声明

Certain matters discussed in this press release are “forward-looking statements”. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements.

。在某些情况下，公司可能会使用“预测”，“相信”，“潜在”，“继续”，“估计”，“预期”，“预期”，“计划”，“打算”，“可能”，“可能”，“可能”，“可能”，“将会”，“应该”或其他表达未来事件或结果不确定性的词语来识别这些前瞻性陈述。

In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the continued commercial success of the Company’s Sunosi® and Auvelity® products and the success of the Company’s efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the Company’s ability to maintain and expand payer coverage; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund the Company’s disclosed clinical trials, which assumes no material changes to the Company’s currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of the Company’s ongoing clinical trials and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of the Company’s current product candidates, including statements regarding the ability of the ACCORD and ADVANCE clinical trials to support the filing of an NDA for Alzheim.

特别是，公司关于趋势和潜在未来结果的声明就是此类前瞻性声明的例子。前瞻性陈述包括风险和不确定性，包括但不限于公司Sunosi®和Auvelity®产品的持续商业成功，以及公司努力获得与solriamfetol和/或AXS-05有关的任何其他指示的成功；公司维持和扩大付款人覆盖范围的能力；公司正在进行的临床试验和公司当前候选产品的预期临床试验的成功率、时间和成本，包括关于开始时间、注册速度和完成试验的声明（包括公司为公司披露的临床试验提供全额资金的能力，假设公司目前预计的收入或费用没有实质性变化），无效分析和中期结果的接收，这些不一定表明公司正在进行的临床试验和/或数据读数的最终结果，以及支持公司当前候选产品提交新药申请（“NDA”）所需的研究数量或类型或结果的性质，包括关于ACCORD和ADVANCE临床试验支持提交阿尔茨海默病NDA的能力。

Investors:Mark JacobsonChief Operating Officer(212) 332-3243mjacobson@axsome.com

投资者：Mark Jacobson首席运营官（212）332-3243mjacobson@axsome.com

Media:Darren OplandDirector, Corporate Communications(929) 837-1065dopland@axsome.com

媒体：Darren Opland公司传播总监（929）837-1065dopland@axsome.com

References

参考文献

Alzheimer’s Association. 2024 Alzheimer’s Disease Facts and Figures.

阿尔茨海默氏症协会。2024年阿尔茨海默病事实和数字。

Tractenburg, R.E. et al. Estimating the prevalence of agitation in community-dwelling persons with Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 2002 Winter;14(1):11-8.

Tractenburg，R.E.等人估计阿尔茨海默病社区居民的躁动患病率。J神经精神病学临床神经科学。2002年冬季；14（1）：11-8。

Porsteinsson, A.P. and Antonsdottir, I.M. An update on the advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother. 2017 Apr;18(6):611-620.

Porsteinsson，A.P.和Antonsdottir，I.M.关于阿尔茨海默病躁动治疗进展的最新信息。专家Opin Pharmacother。2017年4月；18（6）：611-620。

Source: Axsome Therapeutics, Inc.

来源：Axsome Therapeutics，Inc。