A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Maintenance of Effect of NBI-1065845 as an Adjunctive Treatment in Subjects With Major Depressive Disorder (MDD)

The primary objective of this study is to evaluate the efficacy of NBI-1065845 compared with placebo as an adjunctive treatment in delaying relapse of depressive symptoms (maintenance of effect) in participants with MDD.

开始日期2025-08-18

申办/合作机构

Neurocrine Biosciences, Inc.

NCT06963021

/ Recruiting临床3期

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-1065845 as Adjunctive Treatment in Subjects With Major Depressive Disorder (MDD)

The study will evaluate the efficacy of NBI-1065845 compared with placebo as an adjunctive treatment in participants with MDD on improving symptoms of depression.

开始日期2025-05-30

申办/合作机构

Neurocrine Biosciences, Inc.

NCT06966401

/ Recruiting临床3期

A Long-Term, Open-Label Study to Assess the Safety and Tolerability of NBI-1065845 as Adjunctive Treatment in Subjects With Major Depressive Disorder (MDD)

This study will evaluate the long-term safety and tolerability of NBI-1065845 as an adjunctive treatment in participants with MDD.

开始日期2025-04-16

申办/合作机构

Neurocrine Biosciences, Inc.

100 项与 Osavampator 相关的临床结果

登录后查看更多信息

100 项与 Osavampator 相关的转化医学

登录后查看更多信息

100 项与 Osavampator 相关的专利（医药）

登录后查看更多信息

项与 Osavampator 相关的文献（医药）

2025-10-01·PHARMACOLOGICAL RESEARCH

All roads lead to glutamate: NMDA and AMPA receptors as targets for rapid-acting antidepressants

Review

作者: Freudenberg, Florian ; Reif, Andreas ; McKernan, Ruth M ; Dawson, Gerard R ; Reif-Leonhard, Christine

Treatment-resistant depression (TRD) represents a major clinical challenge. Affecting about 30 % of major depressive disorder (MDD) patients, effective treatments for TRD are urgently needed. While depression research and antidepressant (AD) development have long centred on monoaminergic targets, research over the past 35 years has increasingly explored glutamatergic mechanisms. Here we present an extended discussion on developments in glutamatergic drug discovery, focusing on mechanistic convergence between NMDA and AMPA receptor signalling. Beyond established rapid-acting antidepressants (RAADs), such as (es)ketamine and dextromethorphan/bupropion (AXS-05), we highlight novel therapeutic directions involving esmethadone (REL-1017), nitrous oxide, and positive allosteric modulators (PAMs) of NMDA receptors (e.g. rapastinel, zelquistinel, and apimostinel). Moreover, we discuss forward-looking strategies using AMPA receptor PAMs (e.g. osavampator and tulrampator) and targeting of AMPA receptor-interacting proteins. By integrating recent clinical evidence with molecular and physiological findings, we highlight a convergent mechanism across these compounds. This involves increased AMPA receptor activation, triggering BDNF release and mTOR signalling, promoting synaptic strengthening through enhanced AMPA receptor trafficking and dendritic spine formation. Together, targeting glutamatergic signalling represents a transformative path for TRD treatment with high efficacy by more directly modulating pathologically affected signalling modules. These developments place glutamatergic agents at the forefront of next-generation AD strategies.

2024-05-01·CTS-Clinical and Translational Science

Effects of the selective AMPA modulator NBI‐1065845 on the pharmacokinetics of midazolam or ethinyl estradiol–levonorgestrel in healthy adults

Article

作者: Maynard‐Scott, Jessica ; Singh, Jaskaran B. ; Walling, David P. ; Furey, Maura ; Ionescu, Adrian ; Lin, Swan ; Kennedy, Mike

Abstract:

This parallel‐arm, phase I study investigated the potential cytochrome P450 (CYP)3A induction effect of NBI‐1065845 (TAK‐653), an investigational α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor potentiator in phase II development for major depressive disorder. The midazolam treatment arm received the sensitive CYP3A substrate midazolam on Day 1, followed by NBI‐1065845 alone on Days 5–13; on Day 14, NBI‐1065845 was administered with midazolam, then NBI‐1065845 alone on Day 15. The oral contraceptive treatment arm received ethinyl estradiol–levonorgestrel on Day 1, then NBI‐1065845 alone on Days 5–13; on Day 14, NBI‐1065845 was administered with ethinyl estradiol–levonorgestrel, then NBI‐1065845 alone on Days 15–17. Blood samples were collected for pharmacokinetic analyses. The midazolam treatment arm comprised 14 men and 4 women, of whom 16 completed the study. Sixteen of the 17 healthy women completed the oral contraceptive treatment arm. After multiple daily doses of NBI‐1065845, the geometric mean ratios (GMRs) (90% confidence interval) for maximum observed concentration were: midazolam, 0.94 (0.79–1.13); ethinyl estradiol, 1.00 (0.87–1.15); and levonorgestrel, 0.99 (0.87–1.13). For area under the plasma concentration–time curve (AUC) from time 0 to infinity, the GMRs were as follows: midazolam, 0.88 (0.78–0.98); and ethinyl estradiol, 1.01 (0.88–1.15). For levonorgestrel, the GMR for AUC from time 0 to the last quantifiable concentration was 0.87 (0.78–0.96). These findings indicate that NBI‐1065845 is not a CYP3A inducer and support its administration with CYP3A substrates. NBI‐1065845 was generally well tolerated, with no new safety signals observed after coadministration of midazolam, ethinyl estradiol, or levonorgestrel.

2023-01-01·Neuropharmacology

Role of the AMPA receptor in antidepressant effects of ketamine and potential of AMPA receptor potentiators as a novel antidepressant

Review

作者: Hara, Hiroe ; Suzuki, Atsushi ; Kimura, Haruhide

Ketamine exerts rapid and long-lasting antidepressant effects in patients with treatment-resistant depression. However, its clinical use is limited by its undesirable psychotomimetic side effects. Accumulating evidence from preclinical studies has shown that the antidepressant effects of ketamine are dependent on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) activation, which triggers activation of the mechanistic target of rapamycin pathway and brain-derived neurotrophic factor release. Thus, AMPA-R has emerged as a promising new target for novel antidepressants with a rapid onset of action. However, almost all known AMPA-R potentiators carry the risk of a narrow bell-shaped dose-response curve and a poor safety margin against seizures. Our data suggest that agonistic activity is not only related to the risks of bell-shaped dose-response curves and seizures but also to the reduced synaptic transmission and procognitive effects of AMPA-R potentiators. In this review, we describe our original screening approach that led to the discovery of an investigational AMPA-R potentiator with low agonistic activity, TAK-653. We further review the in vitro and in vivo profiles of TAK-653, including its procognitive and antidepressant-like effects, as well as its safety profile, in comparison with known AMPA-R potentiators with agonistic activity and AMPA, an AMPA-R agonist. The low agnostic activity of TAK-653 may overcome limitations of known AMPA-R potentiators. This article is part of the Special Issue on 'Ketamine and its Metabolites'.

项与 Osavampator 相关的新闻（医药）

2025-12-30

·GlobeNewswire-Health Care

XOMA Royalty and Takeda Execute Strategic Royalty Sharing Transaction and Amend Existing Agreement for Mezagitamab

– Takeda regains a majority of XOMA Royalty’s royalty interest in mezagitamab (TAK-079) –– XOMA Royalty will be entitled to payments based on a share of milestones and royalties associated with nine development-stage assets held within Takeda’s externalized assets portfolio – EMERYVILLE, Calif., Dec. 30, 2025 (GLOBE NEWSWIRE) -- XOMA Royalty Corporation (NASDAQ: XOMA), the biotech royalty aggregator, announced today it has amended its collaboration, originally established in 2006, with Takeda through a strategic royalty share transaction. Takeda’s royalty and milestone payment obligations to XOMA Royalty related to mezagitamab will be reduced, and XOMA Royalty will receive payments based on low to mid-single-digit royalties and milestones across a basket of nine development-stage assets that are held within Takeda’s externalized assets portfolio. “We continue to find ways to expand and diversify our royalty and milestone portfolio through creative transactions that are beneficial to both parties,” stated Brad Sitko, Chief Investment Officer of XOMA Royalty. “Takeda and XOMA Royalty have a long history of collaboration. By amending our collaboration, we are able to return a portion of our mezagitamab economics to Takeda, while also expanding and diversifying XOMA Royalty’s portfolio across several interesting early- and late-stage programs.” MezagitamabPrior to amending the collaboration, XOMA Royalty held a mid-single digit royalty and $16.25 million in potential milestones associated with mezagitamab. Going forward, XOMA Royalty will retain a low single-digit royalty entitlement on mezagitamab and up to $13.0 million in milestones. Development-Stage Assets from Takeda’s Externalized Assets Portfolio Osavampator Neurocrine Biosciences is developing osavampator, a potential first-in-class, investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) for patients who have inadequate response to treatment for major depressive disorder (MDD). Volixibat Mirum Pharmaceuticals is developing volixibat, a minimally absorbed, orally administered investigational therapy designed to selectively inhibit ileal bile acid transporter (IBAT), for primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). OHB-607 and five early-stage Oak Hill Bio assets Oak Hill Bio and their partner are developing OHB-607, a recombinant human IGF-1/IGFBP-3 for the prevention of bronchopulmonary dysplasia in premature infants. Additional Oak Hill Bio assets that have the potential to generate royalties address other high unmet need or rare disease areas. REC-4881 Recursion Pharmaceuticals is developing REC-4881, an investigational MEK1/2 inhibitor for familial adenomatous polyposis, a rare tumor predisposition syndrome affecting approximately 50,000 people in the U.S., France, Germany, Italy, Spain, and the UK1. About XOMA Royalty CorporationXOMA Royalty is a biotechnology royalty aggregator playing a distinctive role in helping biotech companies achieve their goal of improving human health. XOMA Royalty acquires the potential future economics associated with pre-commercial and commercial therapeutic candidates that have been licensed to pharmaceutical or biotechnology companies. When XOMA Royalty acquires the future economics, the sellers receive non-dilutive, non-recourse funding they can use to advance their internal drug candidate(s) or for general corporate purposes. XOMA Royalty has an extensive and growing portfolio of assets (asset defined as the right to receive potential future economics associated with the advancement of an underlying therapeutic candidate). For more information about XOMA Royalty and its portfolio, please visit www.xoma.com or follow XOMA Royalty Corporation on LinkedIn. XOMA Royalty Forward-Looking Statements/Explanatory NotesCertain statements contained in this press release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including statements regarding the timing and amount of potential commercial and milestone payments to XOMA Royalty and other developments related to mezagitamab, osavampator, volixibat, OHB-607 and the Oak Hill Bio assets, and REC-4881. In some cases, you can identify such forward-looking statements by terminology such as “anticipate,” “intend,” “believe,” “estimate,” “plan,” “seek,” “project,” “expect,” “may,” “will”, “would,” “could” or “should,” the negative of these terms or similar expressions. These forward-looking statements are not a guarantee of XOMA Royalty’s performance, and you should not place undue reliance on such statements. These statements are based on assumptions that may not prove accurate, and actual results could differ materially from those anticipated due to certain risks inherent in the biotechnology industry, including those related to the fact that our product candidates subject to out-license agreements are still being developed, and our licensees may require substantial funds to continue development which may not be available; we do not know whether there will be, or will continue to be, a viable market for the products in which we have an ownership or royalty interest; and if the therapeutic product candidates to which we have a royalty interest do not receive regulatory approval, our third-party licensees will not be able to market them. Other potential risks to XOMA Royalty meeting these expectations are described in more detail in XOMA Royalty's most recent filing on Form 10-Q and in other filings with the Securities and Exchange Commission. Consider such risks carefully when considering XOMA Royalty's prospects. Any forward-looking statement in this press release represents XOMA Royalty's beliefs and assumptions only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. XOMA Royalty disclaims any obligation to update any forward-looking statement, except as required by applicable law. EXPLANATORY NOTE: Any references to “portfolio” in this press release refer strictly to milestone and/or royalty rights associated with a basket of drug products in development. Any references to “assets” in this press release refer strictly to milestone and/or royalty rights associated with individual drug products in development. As of the date of this press release, the commercial assets in XOMA Royalty’s milestone and royalty portfolio are VABYSMO® (faricimab-svoa), OJEMDA™ (tovorafenib), MIPLYFFA™ (arimoclomol), XACIATO™ (clindamycin phosphate) vaginal gel 2%, IXINITY® [coagulation factor IX (recombinant)], and DSUVIA® (sufentanil sublingual tablet). All other assets in the milestone and royalty portfolio are investigational compounds. Efficacy and safety have not been established. There is no guarantee that any of the investigational compounds will become commercially available. XOMA Royalty Investor Contact:XOMA Royalty Media Contact:Juliane SnowdenKathy VincentXOMA Royalty CorporationKV Consulting & Management+1-646-438-9754kathy@kathyvincent.com juliane.snowden@xoma.com 1 https://ir.recursion.com/news-releases/news-release-details/preliminary-phase-1b2-data-rec-4881-familial-adenomatous

引进/卖出

2025-12-28

·生物药学科普

2026年生物科技五大精选股票

随着2025年生物科技行业经历深度调整与洗牌，市场焦点正从广泛叙事转向具备明确临床价值与商业化路径的差异化资产。基于对管线进展、市场潜力及公司战略的综合分析，行业分析师筛选出五家在2026年具备显著增长潜力的生物科技公司。这些公司覆盖从基因编辑、抗体药物偶联物到中枢神经系统疾病治疗等前沿领域，其关键临床数据的读出与监管里程碑的达成，有望成为驱动股价与行业格局变化的重要催化剂。一、 CRISPR Therapeutics：基因编辑疗法的商业化深化与拓展核心逻辑：随着CRISPR/Cas9技术从概念验证走向商业化，CRISPR Therapeutics凭借其领先的基因编辑疗法已建立起实质性营收基础。公司主打产品exa-cel（与Vertex合作开发）针对镰状细胞病和β-地中海贫血的疗法已在美国和欧洲获批上市，2026年的关键看点在于商业化放量速度及新适应症的拓展。数据与进展：截至2025年第三季度，exa-cel已治疗超过200名患者，早期数据显示持久的胎儿血红蛋白水平提升与输血独立性。公司预计在2026年上半年公布exa-cel在更广泛患者群体（包括老年患者与特定基因型）中的长期随访数据。管线中针对遗传性血管性水肿的体内基因编辑疗法CTX310已进入I/II期临床，初步安全性数据预计在2026年中公布。与Vertex的合作协议确保公司享有exa-cel销售额的分成，分析师预计2026年该产品将为公司带来超过8亿美元的收入。风险与机遇：定价与报销政策仍是影响放量的关键变量，但exa-cel作为潜在一次性治愈疗法，其长期经济效益正逐步获得支付方认可。此外，体内基因编辑平台的验证将打开更广阔的市场空间。二、 Seagen（辉瑞子公司）：ADC领域龙头，协同效应释放价值核心逻辑：作为抗体药物偶联物领域的先驱与领导者，Seagen在被辉瑞收购后，其研发管线与全球商业化能力得到极大增强。2026年，多款ADC新药的获批与已上市产品的适应症拓展将成为主要增长动力。数据与进展：核心产品Padcev（enfortumab vedotin）联合Keytruda用于一线治疗晚期尿路上皮癌的适应症已于2025年获FDA完全批准，2026年将进入快速放量期，分析师预计该适应症峰值销售额有望突破50亿美元。新型TROP2 ADC药物Trodelvy在HR+/HER2-乳腺癌后线治疗中的市场份额持续增长，针对非小细胞肺癌的III期临床试验数据预计在2026年末公布。与辉瑞的研发整合加速了新一代ADC平台的应用，针对实体瘤的新靶点ADC（如CD228）已进入临床阶段。公司ADC技术平台对外授权持续产生里程碑收入，2025年相关收入已超过5亿美元。风险与机遇：市场竞争加剧，尤其是来自第一三共/阿斯利康、吉利德等公司的同类产品。但Seagen凭借先发优势、强大的专利布局以及与辉瑞的协同，有望维持市场领导地位。三、 Neurocrine Biosciences：中枢神经系统疾病治疗的隐形冠军核心逻辑：Neurocrine Biosciences在精神神经疾病领域构建了深厚且多元化的产品组合，其产品线兼具已上市产品的稳定增长与后期管线的巨大潜力。公司出色的商业化执行能力和财务健康度使其成为防守性增长的代表。数据与进展：主力产品Ingrezza（valbenazine）用于迟发性运动障碍，市场份额稳固，且针对抽动秽语综合征的新适应症已于2025年获FDA批准，预计2026年贡献显著增量收入。与AbbVie合作的妇科药物Orilissa（elagolix）在子宫内膜异位症相关疼痛市场表现稳健。管线中最受关注的是用于难治性抑郁症的NMDA受体调节剂NBI-1065845，其II期数据显示出快速且持久的抗抑郁效果，关键III期试验已于2025年启动，首位患者数据预计在2026年下半年公布。公司现金流充沛，无长期债务，为潜在的业务拓展或并购提供了灵活性。风险与机遇：精神神经疾病领域临床试验失败率较高，NBI-1065845的III期结果存在不确定性。然而，该领域未满足需求巨大，任何积极数据都可能带来价值重估。四、 Arrowhead Pharmaceuticals：RNAi疗法的平台价值兑现核心逻辑：Arrowhead凭借其专有的靶向RNAi平台，在代谢性疾病和肝脏相关疾病领域开发了一系列具有高度差异化的候选药物。2026年，多项关键临床数据的公布有望验证其平台的广泛适用性及药物的变革潜力。数据与进展：针对α-1抗胰蛋白酶缺乏症相关肝病的疗法ARO-AAT（tirpasiran）的III期临床试验已完成患者入组，顶线数据预计在2026年第一季度公布。若成功，这将是首个针对该疾病的疾病修饰疗法。用于治疗心血管疾病高危患者的脂蛋白(a)降低疗法ARO-LPA的II期数据令人鼓舞，预计2026年启动III期临床。与安斯泰来合作开发的非酒精性脂肪性肝炎疗法ARO-HSD已完成II期，数据显示出肝脏炎症和纤维化的显著改善。公司平台采用皮下给药，具有患者依从性高、生产相对简便的优势。风险与机遇：RNAi领域竞争激烈，且ARO-AAT的III期结果至关重要，失败将严重影响公司估值。但成功则可能验证其平台在多个肝病领域的应用，并吸引更多合作。五、 Sarepta Therapeutics：基因疗法与精准医疗的持续领跑者核心逻辑：Sarepta在杜氏肌营养不良症及其他罕见神经肌肉疾病领域建立了难以复制的领导地位。随着其基因疗法和RNA平台的持续推进，公司有望在2026年实现多个价值拐点。数据与进展：基因疗法Elevidys（delandistrogene moxeparvovec）用于治疗4-5岁DMD患者已获加速批准，针对更广泛年龄组（2岁以上）的确认性III期临床试验数据预计在2026年中公布，若转为完全批准，市场将大幅扩容。下一代基因疗法SRP-5051（针对外显子51跳跃）的II期数据显示出比现有疗法更高的外显子跳跃效率和肌肉功能改善潜力。管线中针对肢带型肌营养不良症和某些先天性肌营养不良症的基因疗法已进入临床。公司与罗氏的合作提供了重要的资金支持和商业化资源。风险与机遇：基因疗法的长期安全性与疗效持久性仍需更多数据验证，监管审查严格。然而，DMD领域存在巨大的未满足需求，任何积极的临床进展都可能推动公司价值上升。六、总结 2026年生物科技的投资主线将紧密围绕“数据驱动”与“价值兑现”。上述五家公司代表了不同技术路径下的领先者，其共同特点在于：拥有经过验证或极具潜力的技术平台、明确且临近的临床/监管催化剂、以及清晰的市场定位与商业化路径。在行业整体从估值调整走向基本面驱动的阶段，这些具备差异化创新能力和扎实执行力的企业，更有可能穿越周期，为投资者带来超额回报，并推动生物医药行业向下一阶段演进。参考来源： The top 5 stock picks for biotech in 2026: William Blair. Fierce Pharma 2025 公众号已建立“生物药学科普交流群”微信行业交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

抗体药物偶联物临床3期引进/卖出申请上市基因疗法

2025-12-26

·知乎专栏

2025年第三季度最新离子通道药物研发疾病领域进展

在 2025 年第三季度，离子通道仍然是药物发现的活跃领域：多种治疗领域的研发管线均取得了显著进展。下文将按照适应症类型进行梳理，重点呈现关键离子通道靶点、领先候选化合物（小分子、生物制剂、多肽等）、相关疾病领域、研发阶段，以及具有代表性的合作与交易动态。为了更详细地展示这些成果，我们将分三篇文章进行介绍（文末可查看往期内容）。本篇文章重点回顾这一季度离子通道药物的抑郁、精神分裂症等疾病领域进展。抑郁（重度抑郁障碍与产后抑郁）GABAA 受体的正向变构调节剂在抑郁领域的关注度持续上升。在重度抑郁障碍（MDD）领域，两款离子通道调节剂已推进至 III 期：Neurocrine Biosciences 从武田引进了 osavampator（原 S47445），这是一种 AMPA 受体 PAM，可增强兴奋性神经传递，并于 2025 年初在难治性抑郁中启动 III 期试验。Xenon 已启动其 Kv7 开放剂 XEN1101 作为 MDD 辅助治疗的 III 期研究，此前在 MDD 患者中的 II 期试验曾观察到疗效信号（虽然结果并非在所有终点上均显著阳性，但提示对难治性抑郁患者可能有一定获益）。截至 2025 年第三季度，这两项 III 期项目（AMPA PAM 和 Kv7 PAM）均在入组中，体现出“将神经活性离子通道调节剂再利用于情感障碍治疗”的更广泛趋势。Sage/Biogen 围绕 zuranolone 在 MDD 适应证上的高调合作已于 2023 年受挫，当时相关 MDD 试验结果喜忧参半，促使 Biogen 缩减了在该适应证上的投入。不过，Sage（在 Biogen 于美国以外地区的支持下）仍在继续推动 zuranolone 用于产后抑郁以及其他潜在的利基型抑郁适应证。精神分裂症与认知障碍在精神分裂症领域，联合靶向离子通道和神经递质受体是一种新兴策略。Newron 的 evenamide（前文癫痫部分已有讨论）是一种钠通道阻滞剂，正在作为辅助用药评估其抑制异常放电的作用。此外， Neurodia 与 Merck 合作，重启其 α7 烟碱型乙酰胆碱受体正向变构调节剂（PAM）项目。在多年搁置后，他们于 2025 年第一季度在阿尔茨海默病认知功能受损患者中启动该 α7 nAChR 调节剂的 II 期试验，并触发来自默沙东的里程碑付款。这一“回归”颇为意外，说明默沙东认为该项目（可能基于早期数据或新剂型）具有足够潜力值得继续推进。在精神分裂症阴性症状领域，IAMA Therapeutics 正在开发 NKCC1 氯协同转运体阻滞剂（本质上通过调节神经元内 Cl⁻水平以增强 GABA 能抑制张力）。该公司已于 2025 年报告 I 期阳性结果，并获得资金启动其 NKCC1 抑制剂在精神分裂症中的 II 期临床试验。若获得成功，这一策略有望恢复特定神经元群体的兴奋/抑制平衡，从而缓解包括认知功能受损在内的一些症状。神经退行性疾病在阿尔茨海默病和肌萎缩侧索硬化症（ALS）等疾病中，离子通道同样是重要治疗靶点。Axsome Therapeutics 的联合用药 AXS-05（右美沙芬/安非他酮）部分通过 NMDA 受体拮抗发挥作用（其中右美沙芬为 NMDA 通道阻滞剂）。在 ALS 领域，QurAlis 的 Kv7 开放剂 QRL-101（前文提及）已完成首次人体试验阶段的给药；2025 年第三季度，QurAlis 报告称首批 ALS 患者队列给药顺利完成且安全性良好，使得 I 期研究可以推进至更高剂量阶段。任何关于减缓 ALS 进展的信号（即便是初步的）都将备受期待，但相关疗效数据可能还需要一到两年才能完全揭示。运动障碍：原发性震颤（ET）领域Sage Therapeutics/Biogen 的 SAGE-324（一种选择性作用于 α2/3 亚基的 GABAA 受体正向变构调节剂在 2024 年的 II 期原发性震颤研究中未能达到主要终点，项目随即被终止。相对而言，2024 年底 Acadia Pharmaceuticals 与 Saniona 达成授权交易，从后者引进用于原发性震颤的 SAN-711——一款选择性靶向 GABAAα3 亚基的 PAM——交易总金额最高可达 6.1 亿美元（其中 2800 万美元为预付款）。SAN-711（现更名为 ACP-711）截至 2025 年处于 I 期开发阶段，其α3 亚基选择性被认为有望在抑制震颤的同时减少镇静等不良反应（因为 α1 亚基主要介导镇静）。该交易表明，只要靶向足够精准，离子型 GABA 受体调节仍被看好可用于治疗震颤。神经肌肉罕见疾病在 CMT 领域，NMD Pharma 的 ClC-1 氯通道阻滞剂 NMD670 于 2025 年一季度获 CMT1 孤儿药资格，正处于早期临床，主要评估安全性及初步肌力改善信号。Actio Biosciences 以 TRPV4 为靶点开发小分子抑制剂 ABS-0871，已在 2024 年底获得 FDA 孤儿药及罕见儿科疾病资格，并于 2025 年一季度启动健康志愿者 I 期试验，下一步有望进入 CMT2C 患者研究（该病目前无获批疗法）。二者体现出围绕 ClC-1 与 TRPV4 等离子通道遗传学的认知，正加速转化为面向周围神经/神经肌肉罕见病的靶向治疗。交易活动除礼来收购 SiteOne 之外，2025 年第三季度疼痛领域初创企业继续赢得投资者信心。Latigo Biotherapeutics 于 2024 年底完成 1.5 亿美元 B 轮融资，用于推动其 Nav1.8 抑制剂进入关键临床试验阶段；Allay Therapeutics 也获得融资支持，以推进其用于术后疼痛的缓释布比卡因制剂（经典钠通道阻滞剂）IIb 期临床开发，显示即便是重新制剂化的局麻药同样受到市场关注。相比之下，AlgoTherapeutix 于 2025 年 Q3 传来不好的消息：其局部用阿米替林制剂 ATX-01（一种多靶点 sodium channel 以及 NMDA 阻滞剂）在化疗相关神经病变试验中未能显示获益，最终导致该项目被叫停。总体来看，2025 年疼痛领域的特点在于：钠通道抑制剂持续向后期临床和审批阶段推进，同时一批创新给药模式（基因疗法、复方药物、离子通道贴剂等）正在涌现，试图克服以往在安全、有效阻断疼痛传导通道方面所面临的历史性挑战。癫痫管线交易：除 Biogen–Stoke 合作之外，另一项重要交易是 Neurocrine Biosciences 扩大其与 Xenon 的合作关系。在首个 Nav1.6 选择性阻滞剂 XEN901 遭遇挫折之后，Xenon 与 Neurocrine 于 2025 年初将一款具有 Nav1.6/Nav1.2 双重活性的后备化合物推进至 I 期临床。随着这一新一代钠通道阻滞剂进入临床试验，相应的里程碑付款被触发。意大利的 Newron Pharmaceuticals 与 Acadia Pharma 达成合作，支持广谱钠通道阻滞剂 evenamide 作为精神分裂症辅助治疗药物的全球 III 期临床试验开发（evenamide 的作用机制与抗癫痫钠通道阻滞剂存在重叠）。evenamide 的 III 期“Stephen” 试验项目已于 2025 年第一季度获得监管部门放行，体现了离子通道药物在癫痫及精神共病领域的交叉布局与协同价值。除 Acadia–Saniona 围绕 SAN-711 的授权合作外，礼来在 2025 年第二季度曾被拿来举例为“收购 Migraine Therapeutics”的案例（实际上这只是一个用于说明的假设示例——礼来在镇痛领域真正的收购标的是前文提到的 SiteOne）。若以真实案例来看，AbbVie 于 2025 年中收购 Mitokinin，主要布局帕金森病相关的 PINK1 通路（该通路并非离子通道靶点，因此超出本文聚焦范围）。总体而言，2025 年的大额交易更多集中在基因治疗和蛋白病等方向，而离子通道相关交易则相对更聚焦和“点状”：包括 Lilly–SiteOne（疼痛）、Biogen–Stoke（Dravet）、Acadia–Saniona（震颤）、Neurocrine–Takeda（AMPA PAM）等。这也反映出离子通道药物发现往往由具备专门技术积累的中小型生物技术公司主导，待取得关键进展后再与大型制药企业合作推进后期临床与商业化。结语：2025 年第三季度，离子通道药物在多疾病领域持续发力。疼痛方面，Nav1.8 阻滞剂作为新一代非阿片镇痛药完成从概念到 FDA 首次获批，并带动礼来–SiteOne 等一系列交易与跟进管线；癫痫领域，从 Dravet 基因疗法到获得突破性疗法认定的亚型选择性钠通道阻滞剂，精准用药加速落地；CF 中，新一代 CFTR 调节剂已在全球上市应用，而吸入式遗传/离子通道治疗则在安全性与疗效之间仍在寻找平衡。心血管方向虽然项目数量有限，但聚焦于“院外自我终止心律失常”和更安全的房颤复律等明确未满足需求。与此同时，GABA、Kv7、ClC-1 等离子通道/通道相关靶点正被系统引入抑郁、震颤、ALS、CMT 等神经精神与罕见病领域。Biogen–Stoke、Acadia–Saniona、Neurocrine–Takeda 等合作，体现了“小而专”的通道创新与大药企后期开发/商业化能力的互补。整体来看，Q3 2025 的离子通道治疗版图呈现出“多靶点、多机制、多技术”的特点：小分子、ASO、基因疗法、肽类等多种手段并行推进，项目管线从临床前一直延伸到上市与再适应证扩展。离子通道这一曾被视为“难以成药”的靶点家族，正在通过新药获批和关键 III 期成功，证明其临床与商业价值，并持续吸引资本与并购布局。

临床2期引进/卖出临床3期临床成功

100 项与 Osavampator 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16304

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
重度抑郁症	临床3期	美国	Neurocrine Biosciences, Inc.	2025-01-22
难治性抑郁症	临床2期	-	Millennium Pharmaceuticals, Inc.	2018-02-15
抑郁症	临床1期	英国	Takeda Pharmaceutical Co., Ltd.	2015-08-26
抑郁症	临床1期	英国	Neurocrine Biosciences, Inc.	2015-08-26

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05203341 (SAVITRI, Corporate Publications) 人工标引	临床2期	重度抑郁症	183	NBI-1065845 (High Dose)	齋觸淵夢範構膚繭淵齋(選廠鬱鹽壓遞衊膚蓋築) = 蓋鹽網憲網鑰願齋鏇膚願願夢鏇鬱蓋夢艱夢選 (積憲糧顧壓願淵築襯鹹 ) 达到更多	积极	2024-04-23
				NBI-1065845 (Low Dose)	齋觸淵夢範構膚繭淵齋(選廠鬱鹽壓遞衊膚蓋築) = 襯壓蓋廠鹽襯繭築蓋鬱願願夢鏇鬱蓋夢艱夢選 (積憲糧顧壓願淵築襯鹹 ) 达到更多
NCT03792672 (Pubmed \| Transl Psychiatry)	临床1期	-	24	TAK-653 0.5 mg	鹽簾鏇齋襯衊範簾簾顧(觸蓋繭遞願網顧選鹹衊) = 獵艱蓋構觸簾繭醖餘夢糧餘鏇製醖艱鹽鹹鹽積 (構願襯鹽鏇襯鑰淵範獵, 5.98 ~ 32.99)	-	2022-09-24
				TAK-653 6 mg	蓋衊鹽壓積鹽築齋艱築(淵淵積糧鏇觸積鑰鏇簾) = 夢夢築顧觸憲鹽夢膚製製夢網鏇積醖構衊鹽艱 (顧築壓艱淵選壓鹹遞積, 0.51 ~ 2.84) 更多
NCT03792672 (CTgov)	临床1期	-	24	placebo+TAK-653 (Placebo)	積鹹鹹蓋鹽鹽願願願膚(廠鹽廠齋廠製窪鬱憲蓋) = 鑰窪鑰夢齋鬱遞製夢網淵繭積壓夢構築選繭顧 (窪鑰廠醖鏇鑰艱獵醖鬱, 693.1535) 更多	-	2020-07-02
				TAK-653 (TAK-653 0.5 mg)	積鹹鹹蓋鹽鹽願願願膚(廠鹽廠齋廠製窪鬱憲蓋) = 齋鬱襯餘夢製蓋蓋糧鑰淵繭積壓夢構築選繭顧 (窪鑰廠醖鏇鑰艱獵醖鬱, 591.1367) 更多