Cebranopadol hemicitrate

神经精神疾病已成为全球及我国疾病负担中增长最快、挑战最为复杂的领域之一。长期以来，受制于疾病机制高度复杂、病理通路尚未充分阐明以及药物递送受限等多重因素，该领域整体创新产出相对有限。近年来，随着老龄化加速、未满足临床需求持续放大，以及新靶标、新机制和新技术的系统性突破，神经精神疾病正重新回到全球医药创新的核心舞台。本文系统梳理了2025年全球与我国神经精神疾病领域临床具有积极进展的药物，以期为科研人员提供有价值的参考。 神经精神疾病涵盖的疾病种类繁多，包括阿尔茨海默病、帕金森病、抑郁症、焦虑症、精神分裂症等，当前已是全球和我国疾病负担的主要原因。然而，受限于疾病机制复杂、临床终点主观性强、血脑屏障递送困难以及监管路径不确定等多重因素，行业一度陷入高需求、低创新的结构性矛盾。近年来，这一局面正在发生实质性变化。一方面，阿尔茨海默病、帕金森病、抑郁症、精神分裂症等神经精神疾病的未满足临床需求持续放大，叠加老龄化加速、疾病诊断率提升以及社会心理健康重视度上升，使得该领域重新回到全球医药创新的核心视野；另一方面，新靶标、新机制、新技术的系统性突破正在逐步改善神经精神疾病研发的成功率——从β淀粉样蛋白、毒蕈碱受体、免疫-神经轴调控到细胞基因疗法、脑内递送平台和数字化生物标志物，神经精神疾病药物研发正从经验驱动走向机制与技术驱动。在这样的大背景下，2025年神经精神疾病药物研发领域正呈现出蓬勃发展的态势，一系列新的研发成果和趋势不断涌现。 2025年，多个产品披露了积极临床结果，涉及罕见病（Tourette综合征、Rett综合征、多发性硬化、亨廷顿病、发作性睡病）、疼痛、癫痫、注意缺陷多动障碍、抑郁症、阿尔茨海默病、精神分裂症等适应症（表1）。 表1：2025年临床取得积极研究进展的药物详情 Ecopipam 该药是Emalex Biosciences自主研发的用于Tourette综合征治疗的潜在“First-in-class”药物，其作用机制是阻断多巴胺在D1家族受体上的作用。2025年2月，Ecopipam在针对Tourette综合征的Ⅲ期注册性临床研究中取得了积极的初步数据，达到主要和次要疗效终点。这项Ⅲ期研究为一项随机、双盲试验，共招募了167名儿童和49名成人。在为期12周的开放标签期后，服用该药后声音和运动抽动症状减轻的儿童患者被随机分为两组，一组继续服用Ecopipam，另一组在接下来的12周内改用安慰剂。结果显示，当继续服用Ecopipam时，41.9%的儿童症状复发，这一复发率显著低于服用安慰剂儿童的68.1%；次要终点研究分析了成人患者的复发率，与儿童患者的较为接近，41.2%的患者使用Ecopipam后复发，而使用安慰剂的成人患者复发率为67.9%。在研究中，Ecopipam总体耐受性良好。 ALZ-801（Valiltramiprosate） ALZ-801（Valiltramiprosate）：该药是Alzheon开发的一款口服小分子β淀粉样蛋白（Aβ）抑制剂，可抑制Aβ错误折叠，稳定单体，阻断聚集，从而抑制可溶性神经毒性淀粉样蛋白寡聚体的形成。2025年4月，Alzheon公布了ALZ-801治疗携带两个拷贝APOE4基因的早期阿尔茨海默病患者（包括轻度认知障碍及轻度阿尔茨海默病痴呆患者）的关键性Ⅲ期APOLLOE4研究的顶线结果。此次公布的APOLLOE4研究是全球首个专注于APOE4/4纯合子患者的Ⅲ期试验，也是迄今为止针对此类患者进行的最大规模的临床试验。结果显示，在治疗第78周的总人群中，虽然该研究未达到主要终点，但磁共振成像（MRI）扫描结果显示，总人群的脑萎缩减慢，表明ALZ-801具有潜在的神经保护作用。在轻度认知障碍（MCI）阶段（最早症状阶段）阿尔茨海默病亚组中，患者的ADAS-Cog13评分显著下降，并且CDR-SB评分和痴呆残疾评估（DAD）评分的降低具有临床意义。此外，该亚组患者的脑萎缩减缓效果更加显著，海马体体积、全脑皮质厚度和全脑体积指标获益比例分别为26%、35%和22%。总体安全人群中无严重不良反应和死亡案例，未观察到血管源性脑水肿或微出血等淀粉样蛋白相关影像学异常风险增加，但ALZ-801组的退出率（19%）高于安慰剂组（9%）。 NA-921 该药是Biomed Industries公司研发的可穿透血脑屏障的小分子口服制剂，用于Rett综合征的潜在治疗。2025年公司公布了其一项的Ⅱ/Ⅲ期临床试验结果。该研究是一项针对5至20岁女性Rett综合征患者的随机、双盲、安慰剂对照Ⅱ/Ⅲ期临床试验，共招募173例患者，按基线体重分为NA-921组（86例）和安慰剂组（87例），两组患者分别每日2次服用对应药物或安慰剂溶液，持续治疗12周；主要疗效数据显示，从基线到第12周，NA-921组Rett综合征行为问卷（RSBQ）改善值为-5.5，显著优于安慰剂组的-1.6，临床总体印象改善（CGI-I）评分中，NA-921组（3.60）亦优于安慰剂组（3.83）。且临床试验数据表明，与首款获批药物DAYBUE相比，NA-921的副作用发生率大幅降低。 Cebranopadol 该药是伤害感受素/孤儿啡肽FQ肽（NOP）和μ-阿片肽（MOP）受体双激动剂（NMR双激动剂），与阿片类药物相比，具有低成瘾风险。2025年1月，Tris Pharma公布了Cebranopadol用于缓解腹部整形术后中重度急性疼痛Ⅲ期临床试验ALLEVIATE-1的研究结果。ALLEVIATE-1是一项多中心、随机、双盲、安慰剂对照的临床试验，通过与安慰剂相比，评估Cebranopadol对全腹部成形术后中重度急性疼痛的镇痛效果。研究结果显示，安慰剂相比，Cebranopadol 400μg每天一次治疗两天，显著降低疼痛强度，术后44小时疼痛数字评定量表（NRS）曲线下面积（AUC4-48）与安慰剂相比，差异59.2。在安全性方面，Cebranopadol耐受性良好，表现出与安慰剂相当的安全性，最常见的不良事件为恶心。没有发生与Cebranopadol相关的严重不良事件。 ANAVEX 2-73 该药是Anavex Life Sciences开发的口服σ-1受体激活剂和毒蕈碱受体调节剂，旨在通过恢复细胞内稳态，包括增强自噬等作用机制来实现延缓认知衰退这一目的。在2025年阿尔茨海默病协会国际会议（AAIC）上，公司宣布该药的Ⅱb/Ⅲ期ATTENTION-AD扩展研究结果显示，在治疗48周时临床认知能力衰退的进展减缓了36.3%，在SIGMAR1基因野生型患者中临床认知衰退减缓幅度高达49.8%。每日口服一次的ANAVEX 2-73可能成为早期阿尔茨海默病的一种新型疗法，并且可以作为抗β淀粉样蛋白单抗药物的补充或替代品。 COMP360 该药是Compass Pathways开发的迷幻药裸盖菇素疗法。COMP360在难治性抑郁症中的首批Ⅲ期临床数据显示：治疗6周后，患者抑郁评分（MADRS）较安慰剂降低3.6分，达到主要终点。Compass称这一结果具有临床意义和高度统计意义，为其后续上市申请奠定了基础。然而，迷幻药的监管和商业化仍是一大挑战。 NRTX-1001 该药是Neurona开发的一款现货型、异体γ-氨基丁酸（GABA）能中间神经元细胞疗法候选药物，目前正在两项多中心、开放标签Ⅰ/Ⅱ期临床试验中评估其治疗成人耐药性内侧颞叶癫痫（MTLE）的疗效。NRTX-1001通过整合进入失调的神经回路、分泌GABA抑制性神经递质，具有显著且持久地减轻或消除对耐药性局灶性癫痫患者发作的潜力。此外，NRTX-1001还可能避免高度创伤性外科手术相关的神经认知损伤风险。Neurona于2025年4月在美国神经病学学会（AAN）年会上公布了其单侧MTLE试验的最新数据。研究结果显示，在7～12个月疗效终点期间，致残性癫痫发作较基线的中位降幅达92%，12个月终点时受试者应答率（发作减少>75%）为80%（4/5），且所有4例接受18～24个月随访的应答者在接受单次NRTX-1001低剂量给药后均实现了持久的癫痫控制。 AMT-130 该药物是uniQure研发的一种一次性基因疗法，它利用腺相关病毒血清型5（AAV5）载体，通过立体定向脑内输注将一种经过工程改造的microRNA（miHTT）递送到尾状核和壳核。这种microRNA能选择性降低HTT mRNA的水平，从而持续减少突变型亨廷顿蛋白。2025年9月，uniQure公布了其用于治疗亨廷顿病的关键性I/Ⅱ期研究的积极顶线数据。该研究达到了预设的主要终点，与倾向评分匹配的外部对照组相比，高剂量AMT-130在36个月时通过复合亨廷顿病评定量表（cUHDRS）测量显示出统计学上显著的疾病进展减缓。该研究还达到了一个关键的次要终点，即与倾向评分匹配的外部对照组相比，在36个月时通过总功能容量（TFC）测量显示出统计学上显著的疾病进展减缓。然而，尽管此次临床试验研究结果是积极的，FDA突然推翻此前共识，不再认可该试验数据对上市申请的支撑力，其提交上市申请（BLA）的计划或将搁浅。 BPL-003 该药是甲氧色胺苯甲酸盐鼻喷制剂，是AtaiBeckley研发的色胺类5-HT1AR激动剂，用于难治性抑郁症获FDA授予突破性疗法认证。其Ⅱ期数据显示，29天后，接受12mg的BPL-003治疗的患者在MADRS上的分数比基线下降了11.1分，8mg的低剂量水平也优于对照治疗。 【参考资料】 1. Insight数据库, 检索日期: 2026年1月21日. 2. 医药魔方数据库, 检索日期: 2026年1月22日. 3. 药明康德、药渡、药时代等网络公开资源. 本文其它内容请见《全球药物创新快讯》2026年第1期（总第158期）。

Cebranopadol is an investigational first-of-its kind dual NOP/MOP receptor (NMR) agonist which uses a novel approach of activating NOP and MOP receptors to work synergistically to modulate pain In both ALLEVIATE trials cebranopadol demonstrates significant and sustained pain reduction with a differentiated safety pro abdominoplasty and bunionectomy Human abuse-potential studies showing cebranopadol is l ess abusable than oxycodone and tramadol, further support its potential to offer strong pain relief with an improved safety profile MONMOUTH JUNCTION, N.J., March 06, 2026 (GLOBE NEWSWIRE) -- Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company, today announced debut data from its Phase 3 ALLEVIATE-1 and ALLEVIATE-2 studies evaluating the safety and efficacy of cebranopadol, an investigational therapy, for the treatment of moderate-to-severe acute pain in patients following abdominoplasty and bunionectomy surgery, respectively, at the American Academy of Pain Medicine (AAPM) 2026 PainConnect annual meeting. The debut abstract titled, “Results of ALLEVIATE-1 and ALLEVIATE-2 Phase 3 Trials of Cebranopadol, a First-in-Class, Dual NOP/MOP Receptor Agonist for the Treatment of Acute Pain After Abdominoplasty and Bunionectomy,” was presented by Dr. Todd Bertoch, MD, Chief Medical Officer of CenExel Clinical Research, and Principal Investigator on ALLEVIATE-2. “As pain specialists, we often see how inadequately controlled acute pain can linger long after surgery or injury,” said Dr. Todd Bertoch. “If we don’t get ahead of severe pain early, it can become chronic and much harder to treat. These Phase 3 results underscore the potential of cebranopadol to redefine the standard of care for acute pain management.” Cebranopadol is an investigational, first-in-class dual nociceptin/orphanin FQ peptide (NOP) and μ-opioid peptide (MOP) receptor agonist (dual-NMR agonist). By simultaneously activating both receptors, cebranopadol is designed to provide potent analgesia while potentially mitigating many of the risks traditionally associated with preferential MOP agonists. ALLEVIATE-1 clinical trial ( NCT06545097 ) is a Phase 3 multicenter, randomized, double-blind, placebo-controlled study. It enrolled 303 patients undergoing abdominoplasty surgery without liposuction or other collateral procedures across four U.S. sites. Eligible participants were randomized in a 1:1:1 ratio to cebranopadol 400 µg on Days 1 and 2, cebranopadol 400 µg on Day 1 and 200 µg on Day 2 or placebo all administered once daily. The first dose was administered approximately 1 hour prior to abdominoplasty and the second dose approximately 24 hours later. ALLEVIATE-2 clinical trial ( NCT06423703 ) is a Phase 3 multicenter, randomized, double-blind, placebo-and active controlled study. It enrolled 242 patients undergoing unilateral bunionectomy with first metatarsal osteotomy across ten U.S. sites. Eligible participants were randomized in a 1:1:1 ratio to a cebranopadol 400 µg, oxycodone immediate release (IR) 10 mg or placebo. Cebranopadol was administered once daily on Days 1, 2, and 3; placebo was administered at 6, 12, and 18 hours to maintain blinding. Oxycodone 10 mg and placebo were administered every 6 hours. Baseline Demographics and Allocation: In the abdominoplasty study, 303 participants were randomized to treatment at four sites in the U.S., and 292 (96.4%) completed the study. Eleven participants discontinued the study due to adverse events (AEs) (3), lost to follow-up (2), withdrawal of consent (3), and other (3). In the bunionectomy study, 242 participants were enrolled at 10 locations in the Unites States, and 236 (97.5%) completed the study. One participant was discontinued in the oxycodone group for hypersensitivity, which was considered a severe and serious AE. No other participants discontinued or experienced a severe or serious AE. Across the two trials, baseline characteristics were similar among groups. More participants in the abdominoplasty study had a history of substance abuse. Efficacy and Safety Results The primary endpoints in both trials were met, demonstrating an acceptable benefit-risk pro cebranopadol for the treatment of acute pain following abdominoplasty and bunionectomy: In ALLEVIATE-1, the average total pain score area under the curve (AUC 4-48) for patients dosed with 400 µg cebranopadol was significantly less than placebo (LS mean difference 59.2; SE 10.14; p<0.001). In ALLEVIATE-2, the average total pain score area under the curve (AUC 2-48) for patients dosed with cebranopadol was significantly less than placebo (LS mean difference 56.1; SE 13.49; p<0.001) Following abdominoplasty, a significantly greater proportion of patients receiving cebranopadol 400 µg required no opioid rescue medication compared with those receiving placebo (34.7% vs 9.9%; p<0.001). Following bunionectomy, a significantly higher proportion of patients receiving cebranopadol 400 µg required no opioid rescue medication compared with those receiving placebo (57.5% vs 28.4%; p=0.006) Cebranopadol was generally well tolerated and exhibited a favorable safety profile. Nausea was the most common AE across study groups with exception of placebo group in the bunionectomy study. Other AEs included vomiting, constipation, headache, dizziness, hypertension and pruritus. Ketan Mehta, founder and CEO at Tris Pharma added, “Acute postoperative pain remains a significant clinical challenge, and the standard of care has serious associated risks. With our first-in-class dual NOP/MOP receptor agonist, we are taking a fundamentally new approach to pain relief, one that simultaneously targets two distinct pathways of pain modulation to deliver meaningful pain relief with a reduced risk of side effects associated with preferential MOP agonists. These data validate this mechanism of action and reinforce the potential of cebranopadol to address a critical need for safe and effective treatment options.” About Acute Pain Approximately 80 million adults in the U.S. are treated for acute pain every year 1,2 . Acute pain can be caused by injury, invasive surgery, illness, major trauma and burns. It can last up to three months and typically resolves once the underlying cause is treated or healed. Moderate-to-severe acute pain can often only be effectively treated with opioid analgesics, which, while effective, are associated with risks including respiratory depression, tolerance, dependence, misuse, and overdose. However, undertreating severe pain in the immediate period after onset can increase the risk of a patient developing chronic pain 3,4 . About Cebranopadol Cebranopadol is a first-in-class investigational therapy that targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors (a dual-NMR agonist), for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). These receptors are partially homologous to each other, and they play both complementary and distinct roles to modulate pain biology pathways. Studied in over 33 clinical trials in more than 2,200 subjects, cebranopadol’s pro been well characterized in pain management studies. It has demonstrated positive clinical results in acute pain, chronic pain, and diabetic neuropathic pain with a favorable safety profile. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain, and if approved, it could become the first dual-NMR pain-relief therapy with the potential to provide efficacy equivalent to selective MOP agonists such as oxycodone with less risk of misuse or physical dependence, addiction or overdose.  Cebranopadol’s novel mechanism of action has potential in treating patients with substance use disorders (SUDs). Tris plans to continue to evaluate cebranopadol’s potential to help patients break the cycle of opioid addiction.  The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), has awarded Tris a five-year grant of up to $16.6 million to study cebranopadol’s potential to treat OUDs and SUDs.  About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, addiction and disorders of the central nervous system. Tris markets a portfolio of best-in-class ADHD products and is developing a promising pipeline of differentiated near-term drug candidates. More information is available at  and on LinkedIn  @TrisPharma .  Media Contact Jonathan Pappas  LifeSci Communication  jpappas@lifescicomms.com Company Contact Cheryl Patnick  Tris Pharma, Inc.  cpatnick@trispharma.com ________________________ Banerjee S, Argaez C. Multidisciplinary Treatment Programs for Patients with Acute or Subacute Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]. Canadian Agency for Drugs and Technologies in Health. 2019 May 7; PMID: 31498579 Lopez A, Menzie AM, Kenderes M, Rubin JL. A real-world database analysis of the prevalence of pain medication use in the United States. PAIN Reports. 2026 February; DOI: 10.1097/PR9.0000000000001396 McGreevy K, Bottros MM, Raja SN. Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy. European Journal of Pain Supplements. 2012 Nov 11; PMID: 22102847 Sinatra, R. (2010). “Causes and Consequences of Inadequate Management of Acute Pain.” Pain Medicine, 11(12), 1859–1871. doi:10.1111/j.1526-4637.2010.00983.x