A Phase 2 Randomized, Double-blind, Placebo-Controlled Study of the Analgesic Efficacy and Safety of the Subcutaneous Administration of the Anti-NGF Antibody Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis

The primary objective of this study is to determine whether the administration of tanezumab, an anti-nerve growth factor (NGF) antibody, improves pain relief in schwannomatosis patients receiving background non-NSAID therapy.

开始日期2020-04-30

申办/合作机构

The General Hospital Corp.

[+1]

PER-069-15

/ Recruiting临床3期

A PHASE 3 RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, MULTICENTER STUDY OF THE LONG- TERM SAFETY AND EFFICACY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE

开始日期2016-04-01

申办/合作机构-

NCT02709486

/ Completed临床3期

A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE

Tanezumab is a monoclonal antibody that binds to and inhibits the actions of nerve growth factor (NGF). The Nerve Growth Factor Inhibitor (NGFI) class may offer an important breakthrough in the treatment of chronic pain and is under clinical investigation for the treatment of pain associated with osteoarthritis or other chronic pain conditions.
The primary objective of this study is to demonstrate superior efficacy of tanezumab 5 mg and 2.5 mg administered subcutaneously (SC) every 8 weeks versus placebo at Week 24 in subjects with osteoarthritis of the knee or hip. The 2.5 mg dose was shown to provide efficacy benefits with a favorable safety profile when administered intravenously in previous Phase 3 clinical trials. The 5 mg dose is expected to provide added efficacy benefit over the 2.5 mg dose based on data from previous studies.

开始日期2016-03-02

申办/合作机构

Pfizer Inc.

[+1]

100 项与塔奈珠单抗相关的临床结果

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100 项与塔奈珠单抗相关的转化医学

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100 项与塔奈珠单抗相关的专利（医药）

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项与塔奈珠单抗相关的文献（医药）

2026-05-01·DRUGS

Efficacy and Safety of Anti-nerve Growth Factor Monoclonal Antibodies in Managing Chronic Musculoskeletal Pain: A Systematic Review with Network Meta-analysis

Review

作者: Mahgoub, Reham ; Alhasan, Mohammad ; Seah, K T Matthew ; Abouelella, Ahmed ; Ibrahim, Ayman ; Day, Richard O ; Najah, Qasi ; Arendt-Nielsen, Lars ; Bagg, Matthew K ; Al-Tamimi, Mansoor ; Elhadi, Muhammed ; Abuzied, Ola ; Lopez-Olivo, Maria A ; Hamoudah, Ahmed ; Basheer, Eman

BACKGROUND:

Anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) have emerged as a promising new class of analgesics, offering potential benefits in managing particular painful musculoskeletal (MSK) conditions. However, their long-term safety remains uncertain, leading to regulatory non-approval of these agents. This study aims to evaluate the efficacy and safety of individual anti-NGF mAbs compared to other analgesics when treating chronic MSK pain.

METHODS:

Our literature search included PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov through April 25th, 2025. Articles eligible for inclusion were randomized controlled trials (RCTs) comparing one of the human anti-NGF mAbs to other interventions in adults with chronic MSK pain. Primary outcomes evaluated were changes from baseline in pain, physical function, and patient global assessment (PGA) scores, as well as risks of adjudicated arthropathies (AAs) and abnormal peripheral sensation (APS). We used the Cochrane Risk of Bias 2 (RoB-2) tool to assess risk of bias. Pairwise and network meta-analyses were performed using random-effects models. Treatments were ranked using the cumulative ranking curve (SUCRA), and a multi-criteria decision analysis with Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) was applied to integrate all efficacy and safety outcomes. Statistical analyses were conducted in R (v4.3.1) using the meta, netmeta, gemtc, and Multi-Criteria Decision Aiding (MCDA) packages.

RESULTS:

A total of 29 studies, involving 27,747 patients with osteoarthritis or chronic low back pain, were included in this analysis. Compared to placebo, fasinumab showed the highest improvements in pain (standardized mean difference [SMD] - 0.40, 95% CI [- 0.52, - 0.29], p < 0.001) and physical function (SMD - 0.42, 95% CI [- 0.53, - 0.31], p < 0.001), followed by tanezumab (pain: SMD - 0.36, 95% CI [- 0.44, - 0.28], p < 0.001; function: SMD - 0.39, 95% CI [- 0.47, - 0.31], p < 0.001). For safety, both fasinumab and tanezumab demonstrated a significant risk for AAs (risk ratio [RR] 4.7, 95% CI [3.61, 6.13], p < 0.001; and RR 3.84, 95% CI [2.07, 7.14], p < 0.001, respectively) and APS (RR 1.99, 95% CI [1.49, 2.65], p < 0.001; and RR 2.46, 95% CI [1.93, 3.14], p < 0.001, respectively) relative to placebo. While fulranumab was less effective (pain: SMD - 0.25, 95% CI [- 0.42, - 0.07], p < 0.01; function: SMD - 0.25, 95% CI [- 0.43, - 0.07], p < 0.01), it showed better overall safety against placebo relative to both agents, demonstrating a significant risk only for APS events (RR 1.78, 95% CI [1.09, 2.92], p < 0.05).

CONCLUSIONS:

Anti-NGF mAbs, particularly fasinumab and tanezumab, are associated with the greatest levels of pain relief and functional improvement over placebo within this analysis. However, these benefits are counterbalanced by significant risks of joint-related adverse events. Implementation of strict safety protocols is essential when considering these agents for further evaluation.

PROTOCOL REGISTRATION:

PROSPERO ID: CRD420251104612.

2026-05-01·STRUCTURE

Off-target reactivity in clinical monoclonal antibodies

Article

作者: Zhong, Zhe ; Yeon, Sung M ; McGurk, Elizabeth ; Lilov, Asparouh ; Henkel, Cameron ; Jaycox, Jillian R ; Geoghegan, James C ; Huck, John D ; Sackett, Tricia ; Sandberg, Chanita ; Brouillard, Joseph ; Parker, Liz ; Burnina, Irina ; Yandamuri, Soumya S ; LeMay, Allie K ; O'Connor, Kevin C ; Dai, Yile ; Morrill, Morgan ; Ring, Aaron M ; Sivasubramanian, Arvind

Biologics, including monoclonal antibodies (mAbs), are widely used therapeutics due to their high specificity, yet off-target interactions remain an underappreciated risk for safety and efficacy. To systematically assess antibody specificity, we applied rapid extracellular antigen profiling (REAP) to evaluate 174 FDA-approved and clinical-stage antibodies against 6,172 human extracellular proteins. We found a substantial burden of off-target reactivity, with 28% of antibodies exhibiting at least one off-target hit. Structural and biophysical analyses revealed that off-target binding arises from antibody intrinsic properties and epitope mimicry, either within related protein families or across structurally unrelated proteins. We further identified new off-target interactions of tanezumab and engineered its variable domains to eliminate off-target binding while preserving target affinity and developability. These findings highlight the prevalence of specific off-target reactivity in therapeutic antibodies and underscore the importance of evaluating specificity early in biologic drug development.

2026-01-01·Scandinavian Journal of Pain

Analgesic, anti-inflammatory and joint protective effects of ACD137, a selective negative allosteric modulator of TrkA, in models of chemotherapy-induced peripheral neuropathy and osteoarthritis.

Article

作者: Segerdahl, Märta ; Backlund, Maria ; Forsell, Pontus ; Fernandez, Cristina Parrado ; Nordvall, Gunnar ; Sandin, Johan ; Lidell, Veronica ; Rasti, Azita

OBJECTIVES:

The neurotrophin receptor TrkA is a clinically and genetically validated target in pain signaling. Anti-nerve growth factor (NGF) monoclonal antibodies have shown clinical efficacy but with side effects such as rapidly progressing osteoarthritis limiting their use, potentially mediated via inhibition of NGF/p75NTR signaling. Therefore, we sought to identify novel and selective small molecule negative allosteric modulators of tropomyosin receptor kinase A (TrkA) and to verify their analgesic effect in vivo.

METHODS:

We have identified ACD137 as a potent and selective negative allosteric modulator (NAM) of TrkA during a lead optimization program. The potency of ACD137 on TrkA and selectivity over TrkB was determined in cell-based assays. ACD137 was tested for its analgesic and anti-inflammatory effects in a model of chemotherapy induced peripheral neuropathy (CIPN) using paclitaxel and in the mono-iodo acetate (MIA)-induced osteoarthritis model in rats.

RESULTS:

ACD137 demonstrated an IC₅₀-value on TrkA of 1.2 nM and showed approximately 17,300- and 17,600-fold selectivivity for TrkA over TrkB and TrkC, respectively. After oral administration in rats, ACD137 reduced mechanical allodynia in the CIPN model in a dose-dependent manner with maximal analgesic efficacy similar to the effect of gabapentin. In a comparative arthritis study using the anti-NGF antibody tanezumab as comparator, ACD137 reduced both evoked and non-evoked pain behavior as well as inflammation with similar efficacy as tanezumab. Surprisingly, ACD137 demonstrated a significant protective effect against knee joint deterioration, something that was not observed with tanezumab.

CONCLUSIONS:

The data demonstrates that ACD137 is a potent, selective and in vivo active negative allosteric modulator of TrkA exhibiting analgesic effects in models of neuropathic and nociceptive pain. The molecule possesses promising properties for further pre-clinical development.

项与塔奈珠单抗相关的新闻（医药）

2026-07-23

·网易号

疼痛模型研究|神经药理学平台|镇痛药物筛选|神经病理性疼痛评价

疼痛是全球范围内最常见的临床症状之一，严重影响患者的生活质量。据国际疼痛研究协会（IASP）统计，全球约有20%的人口受到慢性疼痛的困扰。然而，现有镇痛药物（如阿片类和非甾体抗炎药）存在成瘾性、耐受性和胃肠道毒性等明显缺陷，开发新型镇痛药物具有迫切的临床需求。神经药理学研究平台的建立，为理解疼痛机制发现和验证新的镇痛靶点提供了关键技术支撑。疼痛的神经生物学机制与药物靶点疼痛信号从外周伤害感受器（nociceptor）产生，经背根神经节（DRG）传入脊髓背角，再经丘脑投射至大脑皮层产生痛觉。根据病理机制的不同，疼痛可分为伤害性疼痛（nociceptive pain）、神经病理性疼痛（neuropathic pain）和炎性疼痛（inflammatory pain）。伤害性疼痛是对实际或潜在组织损伤的正常生理反应；神经病理性疼痛则是由躯体感觉神经系统损伤或疾病引起的异常疼痛，如糖尿病周围神经病变、带状疱疹后神经痛和化疗诱导的周围神经病变。在分子层面，多种离子通道和受体参与疼痛信号的传导和调制。电压门控钠通道Nav1.7、Nav1.8和Nav1.9在外周伤害感受器中选择性高表达，是新一代非阿片类镇痛药物的重要靶点。Nav1.7功能缺失突变导致先天性痛觉不敏感，而功能获得性突变则引起红斑性肢痛症，这一"人类遗传学验证"使Nav1.7成为极具吸引力的药物靶点。此外，TRP家族通道（如TRPV1、TRPA1）、钙通道Cav2.2（N型钙通道）以及嘌呤能受体P2X3也是疼痛药物研发的热点靶点。在调制层面，内源性阿片系统、大麻素系统和去甲肾上腺素/5-羟色胺系统通过下行抑制通路调控疼痛信号的传导。疼痛动物模型的建立与评价镇痛药物的筛选依赖于能够模拟人类疼痛状态的动物模型。在急性疼痛模型中，热板实验、甩尾实验和足底触觉测试（von Frey filament）是评价药物对热痛和机械痛阈值影响的标准方法。这些模型操作简便、重复性好，适合初步药效筛选，但由于涉及的是正常疼痛反应，其对慢性疼痛的预测价值有限。在慢性疼痛模型中，神经病理性疼痛模型是研究最为深入的类别。坐骨神经慢性压迫模型（CCI）、脊神经结扎模型（SNL）和保留性神经损伤模型（SNI）通过不同程度的周围神经损伤，模拟临床神经病理性疼痛的触诱发痛（allodynia）和痛觉过敏（hyperalgesia）特征。化疗诱导的周围神经病变模型（CIPN）则通过给予紫杉醇、奥沙利铂等化疗药物，建立模拟肿瘤患者化疗相关疼痛的模型。在炎性疼痛模型中，完全弗氏佐剂（CFA）足底注射模型和角叉菜胶模型可诱导持续的炎症和痛觉过敏。评价指标通常包括机械缩足阈值（PWT）和热缩足潜伏期（PWL）的变化，以及自发疼痛行为（如抬足、舔足次数）的记录。在国内，部分CRO机构已建立了涵盖急性疼痛、炎性疼痛和神经病理性疼痛的多类型疼痛模型平台，支持从靶点验证到候选药物评价的镇痛药物研发全流程。镇痛药物研发的技术趋势随着对疼痛神经生物学理解的深入，镇痛药物研发正在从传统的"广谱镇痛"向"机制导向的精准镇痛"转变。Nav1.7和Nav1.8选择性抑制剂的开发代表了这一趋势——通过特异性靶向外周伤害感受器，这些药物有望实现有效镇痛的同时避免中枢神经系统副作用。以VX-150为代表的Nav1.8抑制剂在临床试验中已显示出良好的镇痛效果和安全性 profile。此外，靶向神经生长因子（NGF）的单克隆抗体（如tanezumab）通过阻断NGF-TrkA信号通路，在骨关节炎和慢性腰背痛中展现出显著疗效。在非药物靶点领域，神经调控技术（如脊髓刺激、背根神经节刺激）和基因治疗（如沉默Nav1.7的siRNA疗法）也在积极探索中。在CRO服务层面，建立能够同时评价药物对外周和中枢疼痛通路作用的整合性神经药理学平台，对于支持新一代镇痛药物的研发具有重要价值。国内已有CRO机构布局了疼痛模型研究平台，为创新药企业探索非阿片类镇痛新策略提供技术支撑

2026-07-13

·生信新语

IF81.2！协和团队“多组学+单细胞测序+MR”齐上阵！实力登顶国产神刊《STTT》！

! 📌关节疼到走不了路、上下楼梯咔咔响？骨关节炎早已不是老年人专属病痛，国内上亿患者深陷反复止痛却拦不住软骨磨损的困境！今天给大家分享中国医学科学院药物研究所团队发表于《Signal Transduction and Targeted Therapy》的重磅综述，团队整合多组学、单细胞测序、孟德尔随机化等前沿技术，系统拆解骨关节炎细胞器紊乱+炎症双重致病通路，还梳理靶向给药、细胞疗法全新突破口，颠覆传统只止痛的老旧思路，给骨关节炎新药研发打开全新方向。整理好全套26年高分生信发文套路！多组学、单细胞测序、孟德尔随机化发文有诀窍！关注生信新语后台咨询，帮你拆分高分期刊思路，轻松拿下高分医学论文！ ⬇关注生信新语，带你拆解高分期刊 ! 参考文献一、研究背景骨关节炎（OA）全球患病人数近6亿，国内患者超1.3亿，现有止痛药、关节置换只能缓解症状，没法阻止软骨持续退变。过去研究大多单一盯着炎症因子，忽略线粒体、溶酶体、内质网细胞器损伤在病程里的核心推动作用；同时疼痛、软骨破坏、骨重塑联动机制模糊，缺少多维度分子全景解析，临床急需一套兼顾抗炎、护细胞器、长效镇痛的全新治疗框架，这也是本次综述核心要解决的痛点。二、研究方法 📍单细胞/细胞测序操作方式：分离软骨细胞、滑膜巨噬细胞、背根神经节痛觉细胞开展单细胞测序，分群解析不同细胞亚群分子特征优势亮点：区分正常与病变软骨细胞亚群，精准定位肥大化、凋亡型软骨细胞特有基因，厘清痛觉神经元特异表达通道，解决混合细胞样本信号混杂问题。 📍空间转录组操作方式：保留软骨分层原位结构，获取不同区域细胞转录空间分布信息优势亮点：直观看到表层、深层软骨细胞器损伤、炎症信号的区域差异，解释表层细胞异常钙化、深层软骨重度退变的空间发病规律。 📍孟德尔随机化操作方式：依托人群大样本遗传数据，验证炎症、细胞器异常与骨关节炎因果关联，排除混杂干扰优势亮点：区分 “相关” 和 “致病”，解决传统细胞动物实验无法复刻人体真实发病偏差，为靶点临床转化提供人群证据。 ! 研究结果一、骨关节炎的流行病学 🔷人群个体发病差异性别：女性患病远多于男性，每十万人群患病数差距明显年龄：55–64岁为发病峰值，年纪越大患病概率陡增种族：非裔、亚裔人群关节疼痛、功能残疾程度普遍高于白人 🔷可控高危诱因肥胖：BMI超标是膝OA头号可干预诱因，约两成发病与此相关关节旧伤：ACL损伤患病风险翻4.2倍，半月板损伤风险升至6.3倍运动模式：久坐、高强度频繁运动伤关节，适度活动能起到保护效果职业劳损：建筑、务农、渔业等长期负重劳作人群患病风险更高二、骨关节炎预防 🔷两类预防核心逻辑一级预防：从源头规避致病诱因，直接降低患病概率二级预防：针对已有高危因素人群，延缓病情加重 🔷三大可控风险干预方案 🔸肥胖管控（影响力最大）标准：健康BMI 18.5–25，＞30判定肥胖；控在 25以下可减少27%–53%患病风险减重最优方案：饮食 + 运动搭配，只节食易反弹（半数人1年内复胖），只运动难减重但利于维稳进阶手段：认知行为疗法、减重手术，减重效果更持久 🔸膝关节旧伤防护风险现状：半数重度膝伤患者终身患上OA；超50% ACL损伤者10年内发病预防训练：每周2–3次、每次15–20分钟神经肌肉训练，ACL受伤风险减半短板：中断训练后防护效果直接失效 🔸关节过度负荷规避适用人群：膝损伤病史、长期重体力劳动者调整方式：少深蹲、跪地、搬重物，男性患病风险下降15%–30% 关键提醒：膝损伤手术没法抵消创伤带来的OA风险，重点靠护膝运动、避免二次损伤三、骨关节炎诊断 🔷临床症状与查体判断 🔸典型早期表现：持续数周以上膝痛、僵硬、活动受限，症状不断加重，缓解期很短 🔸基础查体指征：活动痛、关节按压痛、摩擦音、轻微积液；高龄、肥胖、膝外伤、家族史为高危佐证 🔸区分鉴别要点单纯OA：膝盖不发热、少量积液，常伴腘窝囊肿、膝内外翻畸形炎症/感染/结晶关节炎：膝盖发烫、积液明显手指赫伯登、布沙尔结节提示全身多关节退变，膝关节OA易加重 🔸短板：早期X光无明显特征，暂无统一早期确诊标准四、促炎细胞因子在骨关节炎中的作用 🔷IL-1（IL-1α/IL-1β）来源：IL-1α为细胞损伤警报；IL-1β由滑膜、巨噬细胞产生，需caspase-1激活损伤机制：结合IL-1RI激活NF-κB，大量降解软骨基质、招募炎性细胞负调控：IL-1Ra、IL-1RII竞争性阻断通路 🔷TNF-α 存在膜结合、可溶性两种形式，作用两类受体 TNFR1：促炎症、诱导软骨细胞凋亡；TNFR2：具备抗炎保护效果联动效应：与IL-1形成正反馈，促血管新生、加重关节炎症 🔷IL-6（双向作用）来源含髌下脂肪垫，和肥胖高度相关两条通路：经典通路护软骨；转信号通路主导损伤，sgp130可阻断危害：上调基质降解酶、打破骨重塑平衡，抑制软骨修复图1 炎症信号通路及其对骨关节炎关节组织影响的示意图五、软骨细胞器在骨关节炎中的作用 🔷线粒体产能特点：软骨低氧，仅25% ATP来自线粒体氧化磷酸化，其余靠糖酵解损伤通路：电子传递链异常生成大量ROS，损伤mtDNA、降低ATP；线粒体新生（PGC-1α通路）不足、受损线粒体堆积线粒体自噬（PINK1/Parkin通路）：正常清除破损线粒体；OA时通路受阻，氧化应激爆发，诱发软骨细胞凋亡图2 线粒体在骨关节炎进展中的作用 🔷溶酶体核心诱因：软骨细胞吞噬羟基磷灰石晶体，破坏溶酶酸性环境连锁损伤：溶酶体膜通透（LMP），组织蛋白酶释放至胞质，切割BID活化t-BID，打通线粒体凋亡通路钙化机制：RUNX2驱动表层软骨异常肥大，基质囊泡生成羟基磷灰石，加重溶酶体损伤图3 溶酶体诱导软骨细胞凋亡的机制 🔷内质网（ER）应激诱因：软骨自我修复时错折叠蛋白堆积，触发未折叠蛋白反应UPR 三条应激通路：PERK、IRE1α、ATF6α；短期激活为保护机制，持续应激上调CHOP、TRB3促凋亡炎症联动：慢性ER应激激活NF-κB/MAPK，大量合成基质降解酶，加速软骨退变图4 内质网应激反应及其在骨关节炎中的影响示意图六、骨关节炎疼痛的成因 🔷外周痛觉纤维分型 Aδ有髓纤维：传导快，负责尖锐刺痛，突触连接脊髓Ⅰ、Ⅴ层二级神经元 C无髓纤维：传导慢，产生烧灼钝痛，分肽能（分泌SP/CGRP，支配骨骼）、非肽能两类，止于脊髓Ⅱ层中间神经元 🔷外周痛觉信号启动机制痛感受器（背根神经节DRG）分布于关节囊、半月板、骨膜等全膝关节组织关键离子通道：炎症因子、ROS激活TRPV1/TRPA1等通道，钙离子内流；Nav通道放大钠电流，生成动作电位 NGF放大痛敏：IL-1、TNF-α刺激关节细胞分泌NGF；结合TrkA/p75受体，上调TRP、Nav、SP、CGRP，让神经更敏感 🔷脊髓突触信号传递伤害感受器释放三类递质：谷氨酸：结合mGlu/iGlu受体，快速传递痛信号 P物质（SP）：作用 NK1受体 CGRP：结合CLR/RAMP1复合受体图5 膝关节疼痛传递概述七、治疗骨关节炎的潜在药物与策略 🔷现有传统药物短板保守用药：NSAIDs、阿片、关节注射（玻璃酸钠/激素/PRP） NSAIDs：仅镇痛抗炎，伤肠胃、肾脏，重度疼痛无效阿片：成瘾、呼吸抑制风险关节针剂代谢快、需反复注射；PRP方案未标准化终末期方案：关节置换，存在感染、假体松动、需二次翻修问题图6 骨关节炎溶酶体功能障碍双重治疗方法的示意，重点是溶酶体酸性恢复和溶酶体膜修复 🔷新型靶向镇痛药物（前沿靶点） 🔸TRP通道抑制剂/激动剂 TRPV1：拮抗剂（NEO6860等）止痛但部分升高体温；辣椒素类激动剂（CNTX4975）局部注射长效镇痛，缺点初期刺痛 TRPA1：拮抗剂改善冷痛、机械痛，无体温副作用，但物种表达差异影响实验结果 TRPM8：低浓度薄荷类缓解热痛，高浓度加重冷敏感，体外实验会促炎症酶分泌 TRPM3：拮抗剂阻断热痛，还能下调 TRPV1/TRPA1敏感性，研发尚处早期 🔸钠通道Nav选择性抑制剂普通钠阻断药副作用大（头晕、心律失常）；Nav1.7、Nav1.8高选择性抑制剂动物实验可止痛、保护II型胶原，人体安全性待验证。 🔸NGF通路抑制剂（临床潜力最高）单抗类（tanezumab、fasinumab）止痛效果优于NSAIDs；机制：阻断NGF-TrkA通路，下调TRP、SP、CGRP降低神经敏化；缺点长期使用或干扰正常神经稳态，Trk选择性外周抑制剂可规避中枢副作用。 🔸神经递质靶向药 CGRP拮抗剂：动物模型有效，OA临床研究偏少谷氨酸受体：NR2B选择性NMDA拮抗剂无精神副作用；mGlu I拮抗剂、II/III激动剂可抑制痛觉传导；KA受体GluK1拮抗剂镇痛效果可观 P物质NK1拮抗剂：动物有效，人体试验无明显止痛作用图7 该图展示了设计用于软骨细胞内网的复杂DDS，这对于缓解骨关节炎中的内质网应激至关重要 ! 文章小结 🎈这篇综述不只是简单汇总过往研究，而是靠多组学、单细胞、孟德尔随机化等全套前沿技术打通骨关节炎从发病机制到新药研发全链条。它戳破传统治疗 “治标不治本” 的短板，明确细胞器紊乱是疾病核心推手，还配套了精准靶向给药、细胞再生两大创新治疗路径。不管是骨科临床医生、新药研发人员，还是长期受关节疼痛困扰的普通人，都能从中看到未来骨关节炎根治的全新希望。如果你也想做多组学、单细胞测序、孟德尔随机化，快速落地高分发文思路，欢迎后台咨询，生信新语一站式帮你搞定！今天的高分医学干货就到这里啦！整理全套26年高分生信发文套路，想要资料的朋友后台私信领取↓ 声明：以上内容是我个人学习生信、解读文献的思路整理，仅用于学习交流与自我总结，并非专业权威解读。若出现理解偏差或专业错误，欢迎大家留言指正交流！ END 往期推荐: IF24.6！安徽医科大学团队“国自然”热点，联合“单细胞测序+空转”实力登顶双1区！ IF81.2！复旦大学团队力作！“多组学+MR+SHAP分析”Buff叠满，实力拿下国产神刊《STTT》！ IF37.0！仅26天见刊！中科院团队“多组学+单细胞测序+机器学习”创新选题再夺《Cell》刊！ IF56.1！中美联合团队“单细胞测序+多组学”再登《Nature》！揭开厌食发病机制~ 分享收藏在看点赞

细胞疗法基因疗法

2026-07-09

·allsci.com

Sparian Biosciences advances non-opioid pain drug toward clinical testing with NIDA support

Sparian Biosciences, a New York-based for-profit company, has received a USD 3.1 million NIDA UG3 grant to advance SBS-147, an oral non-opioid analgesic, into Phase I and Phase IIa clinical trials — a meaningful signal that federal funders are willing to back early commercial-stage development of alternatives to opioids for pain management. SBS-147 targets the arylepoxamide receptor (AEAr), a non-opioid pathway with preclinical activity across nociceptive, neuropathic, and inflammatory pain models. The compound is an oral prodrug derivative of SBS-1000, an intravenous formulation that completed a Phase I trial in healthy volunteers and demonstrated safety, tolerability, and a signal of analgesic activity in the Cold Pressor Test without evidence of opioid receptor engagement — a key differentiator given that pupil constriction, a pharmacodynamic marker of opioid activity, was absent. The grant will fund a Phase I single- and multiple-ascending dose study to characterize the safety and pharmacokinetics of the oral formulation, followed by a Phase IIa dental pain study as a proof-of-concept efficacy endpoint. Principal investigators are Judy Ashworth and Anna Pasternak. The non-opioid analgesic field has attracted substantial industry and regulatory attention, with approved agents including suzetrigine (Journavx), a Nav1.8 sodium channel blocker from Vertex Pharmaceuticals, and tanezumab, an anti-NGF antibody that faced a protracted regulatory path. SBS-147’s AEAr mechanism is distinct from both sodium channel and nerve growth factor approaches, and the absence of physical dependence or respiratory depression in preclinical models positions it as a candidate for both acute and chronic pain indications where opioid risk is a clinical concern. NIDA’s decision to fund a for-profit company’s clinical-stage program through the UG3 mechanism — typically used to support milestone-gated translational development — reflects the agency’s sustained prioritization of non-opioid analgesic development as a public health strategy. Approximately 6.1 million people in the US are estimated to have opioid use disorder, with around 80,000 opioid-related overdose deaths reported annually. Roughly 6% of opioid-naive patients who receive opioids postoperatively become chronic users, a figure that underscores the upstream prevention rationale for non-opioid analgesic alternatives. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.

临床1期临床结果临床2期

100 项与塔奈珠单抗相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D09387	塔奈珠单抗	-	DB12335

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适应症	最高研发状态	国家/地区	公司	日期
骨关节炎	申请上市	欧盟	Pfizer Europe MA EEIG	-
骨转移癌	临床3期	中国	Pfizer Inc.	2015-10-28
骨转移癌	临床3期	日本	Pfizer Inc.	2015-10-28
骨转移癌	临床3期	日本	晖致制药（大连）有限公司	2015-10-28
骨转移癌	临床3期	阿根廷	Pfizer Inc.	2015-10-28
骨转移癌	临床3期	阿根廷	晖致制药（大连）有限公司	2015-10-28
骨转移癌	临床3期	澳大利亚	晖致制药（大连）有限公司	2015-10-28
骨转移癌	临床3期	澳大利亚	Pfizer Inc.	2015-10-28
骨转移癌	临床3期	奥地利	晖致制药（大连）有限公司	2015-10-28
骨转移癌	临床3期	奥地利	Pfizer Inc.	2015-10-28

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02528188 \| NCT02709486 \| NCT02697773 (Pubmed \| Osteoarthritis Cartilage)	临床3期	骨关节炎	4,541	Tanezumab 2.5mg	醖獵餘窪餘衊製餘壓鏇(膚繭製齋構選簾醖繭廠) = 鑰窪鏇衊鑰築憲齋衊艱餘膚齋餘選獵夢獵獵積 (醖醖範鹹淵襯鏇窪築醖 )	积极	2023-12-01
				Tanezumab 5mg	醖獵餘窪餘衊製餘壓鏇(膚繭製齋構選簾醖繭廠) = 網艱鑰醖範襯襯願淵構餘膚齋餘選獵夢獵獵積 (醖醖範鹹淵襯鏇窪築醖 )
NCT02528188 \| NCT02709486 \| NCT02697773 (pivotal phase III interventional studies, Pubmed \| CPT Pharmacometrics Syst Pharmacol)	临床3期	nerve growth factor (NGF)	2,992	Tanezumab 2.5 mg	顧鏇醖鑰簾簾鏇夢夢夢(鏇艱築獵觸鹽製觸觸壓) = 鬱顧餘廠鹹衊繭鏇淵艱蓋鏇衊製網構範顧願鬱 (餘遞襯鑰築鬱願餘膚簾 )	积极	2023-09-01
NCT02609828 (CTgov)	临床3期	癌症疼痛 \| 骨转移癌	156	placebo+tanezumab (Placebo)	獵淵簾艱願憲願齋夢簾(鹽餘膚範範膚衊積獵窪) = 艱選鑰齋顧鹽構獵鑰網餘衊糧夢網鏇構鏇壓鏇 (醖鬱餘衊鏇鹽製艱醖膚, 0.35) 更多	-	2023-01-20
				Tanezumab (Tanezumab 10 mg)	獵淵簾艱願憲願齋夢簾(鹽餘膚範範膚衊積獵窪) = 窪鑰憲餘遞簾糧膚壓鹹餘衊糧夢網鏇構鏇壓鏇 (醖鬱餘衊鏇鹽製艱醖膚, NA) 更多
NCT02528188 \| NCT02709486 \| NCT02697773 (NCT02528188 \| NCT02709486 \| NCT02697773, Pubmed \| Adv Ther)	临床3期	骨关节炎	-	NSAIDs	憲淵膚築築鹽夢膚淵鹽(鏇構簾積鬱襯繭襯餘範) = 選糧醖鑰淵願築蓋鬱願餘憲壓齋簾鹹齋夢夢鑰 (襯網壓壓窪鏇製夢淵襯 )	-	2023-01-01
				Tanezumab 2.5 mg	憲淵膚築築鹽夢膚淵鹽(鏇構簾積鬱襯繭襯餘範) = 觸餘鏇鏇鏇獵鏇製衊壓餘憲壓齋簾鹹齋夢夢鑰 (襯網壓壓窪鏇製夢淵襯 )
NCT02528188 \| NCT02709486 \| NCT02697773 (Phase 3 trials of tanezumab, Pubmed \| Osteoarthr Imaging)	临床3期	骨关节炎	-	Tanezumab	糧製夢窪夢醖構壓醖積(網壓觸膚鏇醖衊齋衊範) = 網遞醖積觸鹽獵廠網醖築網鬱襯獵衊糧鹽鑰鏇 (鹽願艱窪鹽膚鹽簾選鬱 )	-	2022-09-01
NCT02528188 \| NCT02709486 \| NCT02697773 (Pubmed)	临床3期	髋关节炎 \| 膝关节炎	-	Tanezumab	鏇膚築選構製憲餘簾遞(憲鬱糧積壓願鹽獵憲襯) = 鏇繭觸願繭鏇齋窪繭糧遞糧齋構獵艱餘醖鏇餘 (遞廠壓壓遞衊廠鹹醖網 )	-	2022-03-01
NCT02528188 (Pubmed \| J Neurol Sci)	临床3期	骨关节炎	3,021	Tanezumab 2.5mg	廠範壓鬱簾簾糧鏇遞築(願鹹壓構醖積糧顧醖鹹) = 壓膚鏇選憲築製鬱夢選願窪醖鏇選襯網顧醖顧 (築築網鏇衊衊獵壓衊製 ) 更多	积极	2022-02-14
				Tanezumab 5mg	廠範壓鬱簾簾糧鏇遞築(願鹹壓構醖積糧顧醖鹹) = 顧壓網鏇鑰獵範繭艱鹹願窪醖鏇選襯網顧醖顧 (築築網鏇衊衊獵壓衊製 ) 更多
NCT02725411 (Pubmed)	临床3期	腰痛	277	Tanezumab 5 mg	醖構獵選糧膚壓糧蓋衊(齋顧鹹鹽鹹獵顧壓夢獵) = 鬱遞醖獵淵衊窪顧艱夢鑰選憲顧窪顧艱襯鹹蓋 (鹽膚鑰網網繭構憲壓鹹 ) 更多	-	2021-11-17
				Tanezumab 10 mg	醖構獵選糧膚壓糧蓋衊(齋顧鹹鹽鹹獵顧壓夢獵) = 鏇艱蓋艱簾廠築夢壓壓鑰選憲顧窪顧艱襯鹹蓋 (鹽膚鑰網網繭構憲壓鹹 ) 更多
NCT02528188 \| NCT02709486 \| NCT02697773 (ACR2021)	临床3期	骨关节炎	4,541	Placebo	淵鏇顧蓋壓醖觸鏇齋範(獵繭獵膚顧獵廠構齋餘) = 遞顧醖餘齋獵壓襯鑰膚衊艱壓願夢鹽鏇淵製鹹 (繭廠網範獵淵醖鏇廠簾 )	不佳	2021-11-07
				Tanezumab 2.5 mg	淵鏇顧蓋壓醖觸鏇齋範(獵繭獵膚顧獵廠構齋餘) = 廠鏇窪範壓網獵鑰鑰餘衊艱壓願夢鹽鏇淵製鹹 (繭廠網範獵淵醖鏇廠簾 )
NCT02528188 (ACR2021)	临床3期	关节游离体	-	Tanezumab 2.5mg	膚鑰壓積糧鹽網憲夢鹹(鑰餘衊餘齋膚範壓憲襯) = 壓壓繭糧鏇襯廠願淵鑰鹹築網廠廠積窪蓋齋鬱 (積膚構蓋壓艱齋衊觸鹹 ) 更多	积极	2021-11-07
				Tanezumab 5mg	膚鑰壓積糧鹽網憲夢鹹(鑰餘衊餘齋膚範壓憲襯) = 構簾構廠構齋襯廠範鬱鹹築網廠廠積窪蓋齋鬱 (積膚構蓋壓艱齋衊觸鹹 ) 更多