A Multicenter, Phase 2 Study to Assess the Safety and Efficacy of Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer

This Phase 2 study assesses the safety and efficacy of a single injection of Resiniferatoxin versus placebo for the treatment of intractable advanced cancer pain.

开始日期2025-09-01

申办/合作机构

Sorrento Therapeutics, Inc.

NCT02522611

/ Not yet recruiting临床1/2期IIT

An Open-Label, Phase 1b Safety and Efficacy Trial of Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain

Background:
Cancer-induced bone pain (CIBP) is common in people with cancer. Bone cancer can also lead to anxiety, depression, and reduced mobility and quality of life. Researchers believe a research drug called resiniferatoxin (RTX) may be able to help.
Objective:
To learn whether RTX is safe and can reduce cancer induced bone pain.
Eligibility:
People ages 18 and older with CIBP that is not relieved by standard treatments
Design:
Participants will have up to 6 outpatient visits over about 7 months. These will include:
Medical history
Physical exam
Blood and urine tests.
Thermal testing: a disk placed on the skin to test ability to sense temperature in and around the area of pain
Chest x-ray
EKG: stickers are placed on the chest to measure heart signals
ECG: measures electrical activity of the heart
Participants will have 1 inpatient visit lasting 2-4 days. This will include:
Catheter inserted into a vein in the arm. They are given anesthesia, sedation, and x-ray contrast.
A needle is passed through the skin of the back to inject the RTX.
Participants will keep a log of the pain medications they take after surgery.
Participants will be called 1 week and 2, 3, and 4 months after the injection.
Participants will be mailed surveys and questionnaires to complete 2, 3, and 4 months after the injection.

开始日期2025-06-02

申办/合作机构

National Institute of Neurological Disorders & Stroke

NCT05695339

/ Recruiting临床1期IIT

Phase I Open Label Clinical Trial Using Resiniferatoxin, A Non-Opioid Medication, For the Management of Refractory Morton's Neuroma Pain

Morton s neuroma is an irritation of the nerves that affect the feet. People with this condition may have burning or shooting pain in the balls of their feet. They may also have numbness in adjacent areas. These symptoms may become more frequent and severe over time. The pain may become permanent. Current treatments tend to be short-lived, and they do not work in all people. Better treatments are needed.
Objective:
To test a study drug, resiniferatoxin (RTX), in people with Morton s neuroma.
Eligibility:
Healthy people aged 18 and older who have Morton s neuroma and have tried other standard treatments that did not ease their pain.
Design:
Participants will be involved in the study up to 4 months.
They will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They will have X-rays of their affected feet. They will have tests to assess their pain and how their feet react to touch and changes in temperature. They will complete questionnaires about their pain.
RTX is injected into the foot at the site of the nerve pain. Participants will receive a shot to numb the area before the RTX is administered. They will be monitored in the clinic for 4 hours after they receive the RTX.
Participants will receive up to 5 follow-up phone calls per week. Each call will take 5 to 10 minutes. They will be asked about their foot pain and whether they have had any side effects from the RTX.
Participants will return to the clinic 4 weeks after the treatment. Previous tests will be repeated.

开始日期2025-03-13

申办/合作机构

National Institutes of Health Clinical Center

100 项与树胶脂毒素相关的临床结果

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100 项与树胶脂毒素相关的转化医学

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100 项与树胶脂毒素相关的专利（医药）

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3,458

项与树胶脂毒素相关的文献（医药）

2025-12-31·RENAL FAILURE

The efficacy and safety of rituximab monotherapy in the new onset pediatric idiopathic nephrotic syndrome: a randomized controlled clinical trial

Article

作者: He, Si-Yi ; Zhao, Jing-Li ; Dou, Ya-Lan ; Wang, Jing-Jing ; Liu, Fei ; Shen, Hui-Jun ; Zhang, Xiao-Jing ; Fu, Hai-Dong ; Li, Qiu-Yu ; Huang, Ling-Fei ; Lu, Zhi-Hong ; Sheng, Ai-Qin ; Yan, Wei-Li ; Mao, Jian-Hua ; Feng, Chun-Yue

BACKGROUND:

Nephrotic syndrome (NS) is a common form of glomerular disease in children, characterized by a high propensity for relapse. Prolonged use of glucocorticoids (GCs) can result in various side effects. Rituximab (RTX) may be considered as an initial treatment option for primary nephrotic syndrome in pediatric patients.

METHODS:

We conducted a prospective, single-center, randomized controlled trial (RCT) to evaluate whether the initial use of RTX monotherapy is superior to GC therapy in treating pediatric idiopathic NS and to assess its safety. The primary outcome and secondary outcomes were compared between the two groups.

RESULTS:

A total of 24 pediatric patients were included in the study, comprising 19 males and 5 females. After six weeks of treatment, the complete remission (CR) rate in the GC group was significantly higher than that in the RTX group (100% vs 33.3%). Compared with the RTX group, the GC group had a shorter time to first remission (14.25 d vs. 9.5 d). During the follow-up period, none of the patients in the RTX group who achieved CR experienced relapse, with the longest relapse-free duration being 79 weeks. In the GC group, nine patients experienced relapse with the longest relapse-free period being 94 weeks. No serious adverse events occurred in either group. The cumulative steroid dosage was not statistically different between the 2 groups (p = 0.41).

CONCLUSION:

Although the CR rate of children with idiopathic NS treated with RTX alone is significantly lower, the relapse rate among responders to RTX is also lower than that of the GC treatment.

2025-08-01·MODERN PATHOLOGY

The Histologic Spectrum of Rituximab-Associated Common Variable Immunodeficiency-Like Enteropathy

Article

作者: Cheng, Jerome ; Micic, Dejan ; Cao, Wenqing ; Liao, Xiaoyan ; Hakimian, David ; Liu, Xiuli ; Semrad, Carol E ; Kohnehshahri, Mehran N ; Pai, Rish K ; Jafari, Pari ; Salomao, Marcela A ; Alpert, Lindsay ; Westerhoff, Maria ; Zhao, Lei ; Evaristo, Gertruda ; Choi, Won-Tak ; Hart, John ; Graham, Rondell P

Rituximab (RTX) is a monoclonal anti-CD20 antibody widely used to treat B-cell neoplasms and autoimmune conditions. RTX has recently been linked to an enteropathy characterized by diarrhea, malabsorption, and hypogammaglobulinemia, closely resembling common variable immunodeficiency (CVID) enteropathy. We present the first dedicated histopathologic assessment of RTX-associated CVID-like enteropathy. Study inclusion criteria were the presence of diarrhea, weight loss, or other gastrointestinal symptoms in the setting of current/prior RTX use and associated hypogammaglobulinemia. Twenty-two patients (15 male:7 female; mean age at biopsy/resection, 63.4 years) across 9 tertiary medical centers met inclusion criteria and had small bowel (N = 20) and/or colon (N = 17) specimens (biopsies/resections) available for review; 71.4% of specimens dated from ≤5 years of last RTX dose. Cases were systematically evaluated by gastrointestinal pathologists at each institution. Key histologic features in the small bowel included sparse/absent lamina propria plasma cells (N = 10; 50%), intraepithelial lymphocytosis (N = 12; 60%), villous atrophy (N = 11; 55%), increased crypt apoptotic bodies (N = 6; 30%), and active inflammation (N = 5; 25%). Common features in the colon included sparse/absent plasma cells (N = 7; 41.2%), increased crypt apoptotic bodies (N = 7; 41.2%), active inflammation (N = 5; 29.4%), and intraepithelial lymphocytosis (N = 4; 23.5%). Goblet cell loss was appreciated in small bowel and/or colon specimens from 2 patients. Follow-up biopsies (interval, 2 months to 4 years) were available for 7 patients and largely recapitulated the histology of the index specimens, though 1 patient demonstrated improvement in villous blunting and intraepithelial lymphocytosis. In summary, the histologic spectrum of post-RTX CVID-like enteropathy encompasses lamina propria plasma cell depletion, increased crypt apoptotic bodies, small bowel villous atrophy, and goblet cell loss. While the underlying pathophysiology remains uncertain, the clinicopathologic picture may reflect post-RTX B-cell/plasma cell impairment. Although histologic findings may be subtle and variable, pathologists should be aware of this entity and should seek a history of RTX use in patients whose biopsies exhibit these CVID enteropathy-like features.

2025-07-01·Multiple Sclerosis and Related Disorders

Comparison of CSF biomarkers in multiple sclerosis patients treated with natalizumab and rituximab

Article

作者: Hansson, Oskar ; Hellgren, Johan ; Jonsson, Magnus Förnvik ; Ahlström, Isabella ; Svenningsson, Anders ; Källén, Kristina ; Janelidze, Shorena ; Strandberg, Maria Compagno

BACKGROUND:

Patients with relapsing remitting multiple sclerosis (RRMS) treated with the high-efficacy drugs natalizumab (NTZ) or rituximab (RTX) generally show no evidence of disease activity. Currently, there is no head-to-head comparison between NTZ and RTX of neurodegenerative and neuroinflammatory biomarkers in cerebrospinal fluid (CSF).

OBJECTIVES:

To compare CSF biomarkers in a stable RRMS cohort treated with NTZ or RTX. A secondary objective was to explore potential associations between CSF biomarkers, fatigue, and cognition.

METHODS:

This Swedish multicentre cross-sectional study assessed kappa-free light chain (k-FLC) index, oligoclonal bands (OCBs), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in CSF of 30 RRMS patients on NTZ or RTX for at least 24 months. A longitudinal comparison of biomarkers was performed for IgG Indices. Fatigue and cognition outcomes were explored in relation to CSF biomarkers.

RESULTS:

GFAP level was significantly higher in the NTZ group compared to RTX (mean difference (CI): 2 716 (155; 5278) ng/L, p=0.047). NfL concentration did not differ between the groups. OCBs and k-FLC index were present and elevated in 97 % and 87 % of participants, respectively. IgG-index was significantly reduced only for NTZ. No significant associations were found between fatigue, cognition and the biomarkers.

CONCLUSION:

Our results support that intrathecal inflammatory activity is still ongoing in patients with NTZ and RTX. Cross-sectional GFAP might indicate a lower risk for long-term disability in the RTX group. Our data should be interpreted with caution because of small sample size, making it difficult to control for multiple confounders.

项与树胶脂毒素相关的新闻（医药）

2025-05-07

·复星医药

利妥昔单抗撬动儿童肾病治疗新纪元！《RTX治疗儿童肾综50问》专家沟通会圆满落幕

金陵春深聚群贤，儿肾杏林谱新篇！2025年4月26日，“领航前行—利妥昔单抗治疗儿童肾病综合征50问专家沟通会”在南京成功召开。本次会议由国家儿童医学中心复旦大学附属儿科医院、中国人民解放军东部战区总医院牵头，联合海南国际医药创新联合基金会共同主办，复星医药全程支持。会议由复旦大学附属儿科医院的徐虹教授和中国人民解放军东部战区总医院的夏正坤教授担任主席，汇聚高春林、沈茜、蒋小云和刘小荣等十余位国内顶尖儿科肾病学专家，围绕利妥昔单抗（RTX）的精准应用展开深度探讨，为儿童肾病综合征的分子靶向治疗开启新纪元。会议背景：从“激素依赖”到“靶向突破”儿童原发性肾病综合征是儿科最常见的肾小球疾病，大多数患儿对糖皮质激素反应良好，但总体复发风险仍然较高，约50%患儿进展为频复发或激素依赖（FRNS/SDNS），反复激素及其他免疫抑制治疗带来的生长发育障碍、感染风险等问题亟待破解。利妥昔单抗作为靶向CD20的单克隆抗体，近年来在肾病综合征的治疗，尤其在FRNS/SDNS患儿中降低复发率、缩短激素疗程，展现出革命性潜力。本次会议以“50问”形式系统梳理RTX应用的临床难点，直击一线医生痛点，推动治疗规范化。大咖云集：共话“RTX撬动”新格局中国人民解放军东部战区总医院的高春林教授首先分享《利妥昔单抗治疗儿童SDNS回顾性研究》报告，详细介绍了利妥昔单抗在儿童肾病综合征中的最新前沿进展，临床实践存在的问题，进一步展示回顾性研究设计，结合多中心实际病例分析了利妥昔单抗的疗效和安全性初步结果，期待论文正式发表。随后，复旦大学附属儿科医院的沈茜教授对《利妥昔单抗治疗儿童肾病综合征50问》进行了深入解读，从RTX的作用机制、适用病种、剂量调整到治疗后的监测、激素撤减等多个方面进行了系统阐述，囊括六个章节（RTX概览篇、激素依赖/复发篇、NS初治篇、NS耐药篇、不良反应篇、注意事项篇），为临床医生提供实用参考。焦点突破：四大共识引领临床实践初治患儿早期RTX干预获强力证据徐虹/沈茜教授团队发布的国内RTXFIRPedINS研究1显示：初治NS患儿在激素诱导缓解后联合RTX治疗，1年无复发生存率提升至74.4%（对照组30.3%），2年无复发率高达62.8%。这一成果被国际权威期刊《Kidney International Reports》收录，标志着RTX从“挽救治疗”迈向“一线预防”时代。剂量优化与个体化撤减方案针对FRNS/SDNS患儿，2025年KDIGO指南2推荐基于体表面积调整RTX剂量（375mg/m²×1-4次）。患儿在病情稳定且尿蛋白转阴后，应用首剂RTX即可启动糖皮质激素撤减，撤减周期可缩短至3个月；部分患儿诱导缓解阶段，除激素外还使用CNI（他克莫司或环孢素）协同，优先减停副作用显著药物。耐药性肾病治疗新希望国际多中心研究3证实：RTX可提高CNI耐药型SRNS患儿的缓解率，推荐尽早使用，为传统难治性患儿提供突破性选择。国内回顾性病例分析4，同步证实RTX可有效降低CNI 抵抗型 SRNS 患儿尿蛋白，提高血清白蛋白，药物总体耐受性良好。高效降复发、长期省费用国内发表的宁夏地区数据5显示：RTX治疗后患儿月均医疗费用下降32%（1863元→1275元），印证其“高效降复发、长期省费用”的双重价值。争议与挑战：精准治疗仍待探索专家们结合自身丰富的临床经验，分享了利妥昔单抗在不同场景下的应用经验和见解，部分议题仍待探索：RTX治疗无效的定义：NS患儿在复发后，再次使用RTX仍可获得缓解，建议明晰RTX治疗无效的定义；患儿维持缓解的策略：定期输注RTX vs 复发后按需治疗，需更多高质量循证验证；生物标志物指导用药：CD19+ B细胞重建与复发无直接关联，如何预测复发仍需探索；RTX破局万象新，靶向治疗启华章利妥昔单抗彻底撬动儿童肾病综合征的治疗逻辑——从激素反复撤减的漫长拉锯，到精准狙击B细胞的靶向突破；从“谈激素色变”的沉重负担，到“免激素、低复发”的自由新生。本次会议以循证为基石，以临床需求为导向，为儿童肾病综合征治疗树立了新标杆。随着RTX应用的不断优化，更多患儿将迎来无复发、免激素的健康未来。参考文献：[1] Liu J, Deng F, Wang X, et al. Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome. Kidney International Reports. 2024;9(5):1220-1227.[2] Floege J, Gibson KL, Vivarelli M, Liew A, Radhakrishnan J, Rovin BH. KDIGO 2025 Clinical Practice Guideline for the Management of Nephrotic Syndrome in Children. Kidney International. 2025;107(5):S241-S289.[3] Chan E Y, Sinha A, Yu E L M, et al. An international, multi-center study evaluated rituximab therapy in childhood steroid-resistant nephrotic syndrome[J]. Kidney International, 2024, 106(6): 1146–1157.[4] 余思澄, 刘佳璐, 刘娇娇, 等. 利妥昔单抗治疗儿童CNI抵抗型激素耐药型肾病综合征的短期疗效[J]. 中华儿科杂志, 2025, 63(2): 185–189.[5] 杨武, 王小娥, 顾佳乐, 等. 宁夏地区利妥昔单抗治疗儿童原发性肾病综合征的开展及疗效分析. 临床肾脏病杂志. 2024;24(2):103-107.仅供医药学专业人士阅读，材料编码：P-20250429-004本材料的目的在传递前沿信息，不构成对任何药物或诊疗方案的推荐和宣传，非广告用途；本资料所含的信息不能替代医疗卫生专业人士提供的医疗建议，具体疾病诊疗请遵从医疗卫生专业人士的意见或指导

2025-04-21

·药智网

疼痛！有望成为下一个重磅市场

意大利医史学家卡斯蒂廖尼在《医学史》中指出，医学诞生于人类对痛苦的感知与缓解的渴望，疼痛研究始终是医学的核心命题。当前全球疼痛市场规模持续扩大，甚至被资本市场视为继减重药之后的医药新风口。现实案例印证了这一需求：年轻产妇分娩时急切要求无痛注射，耄耋老人临终前因止痛药失效饱受骨病折磨。数据显示，某三甲医院妇产科无痛分娩率已达85%，折射出现代社会对高效、安全止痛方案的迫切期待。临床期待着即兼顾疗效，又低副作用与高安全性的跨时代产品上市。2025年1月30日，Vertex Pharmaceuticals旗下FIC疗法Suzetrigine（VX-548）获FDA批准上市，用于治疗成人中至重度急性疼痛，该药为FDA批准的首款新机制的非阿片类止痛药物，FDA评价其或将推动疼痛管理进入了一个全新的时代。四大因素疼痛管理成为下一“风口”纵观历史，每个爆款新药都有着相似的底层逻辑，而疼痛之所以能被资本市场誉为下一个减重市场，其原因也类似，甚至更强。1. 庞大患者规模根据《中国疼痛防控与健康促进战略蓝皮书：中国疼痛医学发展报告（2020）》，我国慢性疼痛患者超过3亿人，且每年以1000万～2000万的速度在快速增长，患者人群有年轻化趋势。而另一方面，美国作为止痛药使用频率最高的国家，2020年数据显示，每两名美国成年人就拥有一张阿片类药物止痛处方，且阿片类药物的使用居全球之最。疼痛诊疗认知与止痛药使用犹如一把双刃剑，很难把控其中平衡点。2. 长久的用药周期对于疼痛而言，多数人认为其主要是由疾病所致，病在前，痛在后，但这既对也不对。与肥胖类似，如今的疼痛已不仅仅是一种症状，更是一类疾病，2018年世界卫生组织已将慢性疼痛列为独立疾病。而临床上伴随长期疼痛的疾病比比皆是，例如脊柱源性疼痛、软组织疼痛、神经病理性疼痛以及癌症性疼痛。某种层面来看，急性疼痛可以消失，但大部分慢性疼痛疾病无法治愈，患者往往需要长期服用止痛药，比之减重市场的用药周期与用药频率，明显更高。以DPN患者为例，在临床试验中，福泰制定的时间长达12周。不过，在实际生活中，不少慢性疼痛患者服用止痛药的时间远远大于12周。《Best Pract Res Clin Rheumatol》上的一项研究显示，有80%慢性疼痛患者服用止痛药物超过一年时间。3. 迫切的临床需求尽管临床上用于疼痛管理的药物与治疗方法很多，但其均存在着临床局限性：对于非甾体抗炎药而言，其虽不具备成瘾风险，但其止痛效果较差，且长期使用还会有胃肠道出血与肾损伤‌风险。对于阿片类药物（如芬太尼）虽然止痛效果好，对癌痛有效，但长期使用却有极大的成瘾风险，对呼吸、胃肠功能等非痛觉相关中枢系统产生抑制。更关键的是，现有疼痛管理药物还存在明显的靶向性不足，无法精准区分病理性和生理性疼痛信号，导致30%～50%神经病理性疼痛患者疗效不佳。因此，无论是临床上，还是院外市场，疼痛管理领域都存在着对更有效、更安全的疼痛治疗方法的巨大需求。4. 强烈的支付意愿长期疼痛会削弱神经自控力，疼痛程度与持续时间直接推高患者对止痛药物的依赖度和支付意愿。人类为此曾尝试过诸多非常规手段：公元46年，古罗马医师拉杰斯首创电击止痛法，将活体电鳐置于患者患处放电至麻木，认为可激发内啡肽镇痛；19世纪英国化学家戴维则发现吸入"笑气"（一氧化二氮）既能致幻又能缓解智齿剧痛，由此开创气体麻醉先河。5. 上涨的疼痛认知从医学的角度上看，这些对疼痛的轻视和忍耐是一种危险的行为。对于病源性疼痛，及时进行治疗干预是关键，而对于部分无法避免的疼痛，疼痛控制则是提升患者生活质量的有效手段。随着时代进步，大众对疼痛管理的认知也水涨船高，非甾体类药物与强效阿片类药物也逐渐被大众接受。总而言之，疼痛市场与减重市场都有着很多相类似的点，长期来看，明显具备成为爆品的潜力。时代变化20年需求迎来希望截至目前，临床上用于治疗疼痛的常见用药主要有两大类，第一类为非甾体类的消炎药，比如日常熟知的布洛芬和阿司匹林，其主要用于牙齿疼，肌肉酸痛等外周部位的炎症或外伤引起的疼痛；第二则是阿片类止痛药，代表药物有吗啡、芬太尼、可待因，因其可以阻断疼痛信号向脊髓与大脑的传递，因此理论上其止痛效果往往更强。而如今相对成熟的临床止痛药应用，却也并非一蹴而就，在人类与疼痛漫长的抗争中，无数凝聚了人类智慧的镇痛药物应运而生。有的镇痛药（阿司匹林）现已有了别的用武之地，而有的镇痛神药却消失在了历史长河中，更有的止痛药则是因其滥用风险被世界各国严格管控。图片来源：博药时至今日，止痛药领域的发展路径一方面可以说是围绕非甾体抗炎的有效性与胃肠道反应演变，而另一方面则是围绕如何降低阿片类药物成瘾性推进，期间诞生的各类新药互相弥补局限性，却又不断创造局限性，近200余年里，并没有哪款止痛药药堪称完美。直到2025年首款非阿片类药物的上市，让该领域内研究者看到了新的希望。综合临床应用场景来看，尽管阿片类镇痛药让人谈之色变，但其却是综合镇痛效果、心血管和肾脏副作用等方面，是现阶段疼痛医学的毫无疑问的基石药物，而COX-2特异性抑制剂优势渐显，逐渐有了替代传统非甾体消炎药的潜力，成为患者止痛选择的新趋势。多年来，阿片类镇痛药不仅占临床用药的最多席位，且占有绝对多的市场份额，2022年镇痛类药物PDB样本医院销售额为53.65亿元，仅地佐辛、舒芬太尼、瑞芬太尼和布托啡诺4款阿片类镇痛药的合计销售额就达36.78亿元，占市场份额的68.56%。图片来源：德邦证券但很明显，阿片类镇痛药绝非疼痛管理市场的最终归属，20年里无新机制止痛药上市也并不代表现有临床治疗已趋于完美，事实上临床上仍迫切需要一款止痛效果好、安全性佳、无成瘾性、顺应性良好、可用于慢性疼痛（如癌痛）的划时代新药。新药助力非阿片药时代来临尽管疼痛管理市场历经200余年发展，但至今，止痛药的新药研发方向仍与过去并无太大区别，绝大多数新药仍以非甾体药物优化、阿片类药物迭代两大方向，唯一不同的是，随着基础研究水平的上涨，一些拥有全新止痛机制的非阿片类新药逐渐诞生，某种层面上推动领域进入了一个全新的阶段。作为最被临床与市场寄予希望的方向，非阿片类镇痛药在过去几十年间引无数药企扎身其中，却又不断经历失败，仍不愿放弃。2006年，辉瑞花费5亿美元买下一款选择性神经生长因子（NGF）抑制剂。然而，经过十几年的研发，等待辉瑞的却是失败。2021年3月，FDA以1:19票否决了这款药物的上市申请，辉瑞不得不终止这款药物所有全球开发项目。2016年，梯瓦与再生元就NGF抑制剂Fasinumab达成2.5亿美元的研发协议，然而在其针对糖尿病周围神经病变、纤维肌痛的临床试验相继失败后，2022年再生元也选择了暂停Fasinumab的研发。2018年，已经完成三个2期临床的VX-150，虽概念性地证明了NaV1.8抑制剂在急性、慢性和神经性疼痛中的止痛作用，但由于疗效和副作用方面的原因，最终被Vertex终止。在过去的20年时间里，围绕着新型镇痛药的研发，上述类似的失败案例还有很多。可以说，过去药企们针对新型镇痛药物的研发，一直是在黑暗中前行。但这几十年对非阿片类药物的新药摸索的过程中也诞生了不少充满希望的细分赛道，有效地推动了疼痛管理新药研究的巨大进步。部分“非阿片类药物”的机制与代表药物类别作用机制代表药物乙酰苯胺类抑制中枢神经系统中前列腺素的合成对乙酰氨基酚(扑热息痛)、丙帕他莫COX抑制剂抑制COX，减少前列腺素的合成氟比洛芬酯、酮咯酸选择性COX2抑制剂抑制COX-2，减少前列腺素的合成帕瑞昔布钠、塞来昔布a2肾上腺素能受体激动剂作用于中枢和外周神经系统的a2肾上腺素能受体右美托咪定、可乐定NMDA受体拮抗剂抑制NMDA受体活性，减少兴奋性神经递质释放氯胺酮钙通道阻滞剂调节中枢神经系统钙通道，减少神经递质的钙依赖性释放VX-548TRPV1抑制剂阻断TRPV1通道的激活来发挥作用，从而实现止痛效果MTX-071NGF抑制剂抑制NGF及其受体，阻断信号传导来发挥作用Fasinumab、TanezumabWNT信号通路阻滞剂Wnt抑制剂通过调节神经元的兴奋性和脊髓突触可塑性来缓解疼痛/ATR2拮抗剂抑制P38MAPK和ERK-MAPK信号通路来缓解神经病理性疼痛TRD-205选择性CCR2拮抗剂抑制炎症和疼痛信号的传递来发挥作用CNTX-6970内源性大麻素下的FAAH通过促进内源性大麻素释放或使用外源性大麻素配体可发挥一定的镇痛作用CC-97489NTRK1抑制剂抑制NTRK1激酶的活性，阻断神经生长因子（NGF）与其受体的结合VC004、FB-1003数据来源：公开数据整理据药智数据显示，目前全球领域有超过300余种疼痛管理相关新药在研，其中除乙酰苯胺类、选择性COX2抑制剂与阿片类药物外，也有不少新生代的非阿片类药物在研，比如NaV1.8抑制剂、Nav1.7抑制剂、TRPV1抑制剂、FAAH抑制剂、NGF抑制剂等。NaV1.8/1.7抑制剂遗传研究表明，人体内一共发现9个钠通道，分别为Nav1.1-Nav1.9，其中1.7和1.8仅在周围神经中表达。在感受疼痛时，Nav1.7通道率先启动，然后Nav1.8通道在疼痛信号沿着神经传导时启动，因此在疼痛管线新药研究中，该两个靶点的相关新药研究被寄予厚望。随着研究的深入，Nav1.7抑制剂在临床试验中的表现不尽如人意，靶点占位不足、生物利用度差等问题导致其在实际应用中存在较大局限性，最终使得Nav1.7作为镇痛药物开发的靶点逐渐被取代，研究者们将注意力转向了Nav1.8这一亚型。Nav1.8主要表达于伤害感受神经元上的河豚毒素不敏感型钠通道，在外周神经系统的痛觉信号传导中起着关键性作用，是疼痛治疗的高选择性作用靶点，而且，由于Nav1.8不参与中枢神经相关的活动，Nav1.8抑制剂不会对运动功能产生影响，也不会存在成瘾性问题。2025年1月30日，FDA批准了一款名为Suzetrigine（VX-548）的新型止痛药。成为20多年来首个全新作用机制的止痛药物，即不通过阻断阿片类受体而达到镇痛目的，避免了以往药物成瘾现象，兼顾有效性与安全性。有效性方面，在过去对比普瑞巴林的临床2期试验中，疗效组VX-548的治疗者组在第12周时疼痛评分较基线降低了-2.02，止痛效果与普瑞巴林相当。安全性方面，Vertex耐受性良好，不良事件（AEs）发生率为22.9%，大多数AEs为轻度至中度，无严重不良事件（SAE）与VX-548相关，且并未出现因AEs导致治疗中断的情况。VX-548的上市，成功为Nav1.8靶点打开了想象空间，使得该领域内众多药企在成药性验证方面有了足够的底气。而在Nav1.8抑制剂的研发历程中，也充满艰辛与困难，虽然目前关于NaV1.8抑制剂的代际划分尚未形成完全统一的定义标准，但从产品优势替换层面仍可初步归纳为如今的三代产品。第一代NaV1.8抑制剂：以VX-128、VX-150等早期开发的靶向NaV1.8通道的化合物为主，主要通过阻断该通道的电压门控特性来抑制外周痛觉神经元信号传导，开创了选择性阻断NaV1.8通道的先河，但由于该阶段产品选择性不足、代谢稳定性较差等问题‌，多款新药被迫终止。第二代NaV1.8抑制剂：主要在早期化合物基础上对选择性和药效进行了优化改进，使其具有了更强的靶点结合能力和更低的脱靶效应，尤其是在NaV1.8抑制剂的安全性提升明显。第三代NaV1.8抑制剂：目前公开资料中并未对其定义的明确阐述，仅出现于福泰制药的相关管线宣传中，但参考过去靶向抑制剂的迭代逻辑，第三代产品或会在有效性、安全性、耐药性与特殊适应症层面形成差异化。药品名称产品分类靶点原研单位全球最高阶段中国最高阶段管线状态VX-584第二代SCN10A福泰制药批准上市暂无活跃VX-150第一代SCN10A福泰制药临床Ⅱ期暂无终止LTG-001/SCN10ALatigo Biotherapeutics临床Ⅱ期暂无活跃VX-993第三代SCN10A福泰制药临床Ⅱ期暂无活跃JMKX-000623第一代SCN10A上海济煜医药科技有限公司奥立安药厂临床Ⅱ期临床Ⅱ期活跃HRS4800第一代SCN10A江苏恒瑞医药股份有限公司临床Ⅱ期临床Ⅱ期活跃PF-4531083/SCN10A辉瑞临床Ⅱ期暂无活跃PF-06305591/SCN10A辉瑞临床Ⅰ期暂无终止VX-961第一代SCN10A福泰制药临床Ⅰ期暂无-VX-128第一代SCN10A福泰制药临床Ⅰ期暂无终止VX-973第三代SCN10A福泰制药临床Ⅰ期暂无活跃FZ008-145第一代SCN10A广州费米子科技有限责任公司健康元药业临床Ⅰ期临床申请活跃LTG-305/SCN10ALatigo Biotherapeutics临床Ⅰ期暂无活跃MK-5661/SCN10A默沙东临床Ⅰ期暂无活跃STC-004/SCN10ASiteOne Therapeutics Inc临床Ⅰ期暂无活跃HBW-004285第一代SCN10A成都海博为药业有限公司临床Ⅰ期临床Ⅰ期活跃ODM-111/SCN10A奥立安药厂临床Ⅰ期暂无活跃HRS-2129第二代SCN10A山东盛迪医药有限公司临床Ⅰ期临床Ⅰ期活跃HBW-004-03/SCN10A成都海博为药业有限公司临床申请暂无活跃CN114437062A/SCN10A成都海博为药业有限公司临床前暂无活跃数据来源：药智数据截至目前，全球还有10余款Nav1.8靶向药在研，其中福泰制药作为领域开拓者，既是技术迭代的主要推动者，也是管线布局数量最多的企业。国内企业而言，济煜医药、恒瑞医药、健康元与海博为药业则均有不同阶段与技术的布局。产品分类药品名称靶点原研单位全球最高阶段中国最高阶段管线状态第一代VX-150SCN10A福泰制药临床Ⅱ期暂无终止VX-961SCN10A福泰制药临床Ⅰ期暂无终止VX-128SCN10A福泰制药临床Ⅰ期暂无终止第二代VX-584SCN10A福泰制药批准上市暂无活跃第三代VX-993SCN10A福泰制药临床Ⅱ期暂无活跃VX-973SCN10A福泰制药临床Ⅰ期暂无活跃数据来源：药智数据TRPV1抑制剂TRPV1是一种非选择性阳离子通道，属于瞬时受体电位（TRP）离子通道家族的香草素亚家族。其最初从辣椒中被发现，因此也被称为辣椒素受体或香草素受体1。随着研究深入，TRPV1在许多疼痛传导途径的上游区的调节功能被证实，因此TRPV1成为治疗疼痛的新靶点，尤其是针对慢性疼痛，可有效避免药物成瘾和大量副作用。而对于TRPV1靶点，其最初载体其实是TRPV1激动剂，辣椒碱也被美国药典收录，但后来由于其诸多不良反应，比如灼热感、数天至几星期后会导致痛觉丧失，缺乏对有害刺激的反应，之后TRPV1抑制剂逐渐成为新的研究重点。目前，市面上已有部分新型TRPV1靶向制剂被陆续报道，其在研发数量上也是仅次于NaV抑制剂的存在，在非阿片类止痛药领域拥有不错的临床价值。据药智数据显示，全球TRPV1靶向药领域仅有Qutenza与Zucapsaicin获批上市，前者用于成人患者治疗足部与糖尿病周围神经病变（DPN）相关的神经性疼痛及治疗带状疱疹后遗神经痛引起的神经病理性疼痛；后者则用于骨关节炎。药品名称适应症场景原研单位全球最高阶段管线状态RTX-GRT7039骨关节炎疼痛格兰泰临床Ⅲ期活跃瑞尼毒素 Resiniferatoxin癌性疼痛;骨关节炎疼痛Sherrington Pharmaceuticals Inc临床Ⅲ期活跃伏卡赛辛 Vocacapsaicin术后疼痛Concentric Analgesics Inc临床Ⅲ期/SAF-312慢性疼痛;牙痛;眼痛;眼表疼痛诺华临床Ⅱ期活跃ACD-440周围神经痛;疼痛;神经病理性疼痛AlzeCure Pharma AB临床Ⅱ期活跃NEO-6860骨关节炎疼痛Neomed Institute临床Ⅱ期/V-116517带状疱疹后遗神经痛;流感病毒感染;疼痛;骨关节炎疼痛Purdue Pharma LP;盐野义制药临床Ⅱ期/DWP-05195带状疱疹后遗神经痛大熊制药临床Ⅱ期/GR-705498偏头痛;慢性疼痛;牙齿疾病;疼痛葛兰素史克临床Ⅱ期/JTS-653带状疱疹后遗神经痛Japan Tobacco Inc临床Ⅱ期/AZD-1386创伤后神经痛;带状疱疹痛;术后疼痛;神经痛;骨关节炎疼痛阿斯利康临床Ⅱ期/MK-2295术后疼痛默沙东临床Ⅱ期/JM2947疼痛JMackem Co Ltd临床Ⅰ期活跃玛伐曲普 Mavatrep疼痛强生临床Ⅰ期/ABT-102术后疼痛;炎症性疼痛;疼痛雅培临床Ⅰ期/PF-3864086疼痛辉瑞临床Ⅰ期/GRC-6211牙痛Glenmark Pharmaceuticals SA临床Ⅰ期/AMG-517疼痛安进临床Ⅰ期/BSEN-760慢性疼痛Bsense Bio Therapeutics Ltd临床前活跃数据来源：药智数据而在研药物层面，全球临床阶段用于疼痛管理的TRPV1靶向药接近20个，但其中仅有少部分管线的状态处于积极阶段，最有望上市的产品有两款，分别是格兰泰的RTX-GRT7039与Sherrington的Resiniferatoxin，均处于临床Ⅲ期阶段。后者更是在2024年5月获得了FDA的突破性疗法认定，其在降低疼痛以及安全性方面具有显著效果。TRPV1抑制剂对比NaV1.8抑制剂，其在作用机制、靶点特性及临床应用场景均存在显著差异性，TRPV1抑制剂主要抑制伤害性热刺激和炎症介导的痛觉敏化，主要应用于炎症性疼痛、慢性疼痛等领域，而NaV1.8抑制剂则直接阻断痛觉神经元的电信号传导，适用于急性疼痛和神经病理性疼痛。‌因此，严格意义上来讲，TRPV1抑制剂与NaV1.8抑制剂并非竞品，反而有望在未来形成协同止痛机制，也是被研究界寄予厚望的止痛技术。NGF抑制剂近1个世纪以来，学者们关注并不断揭示神经营养因子（Neurotrophins）在外周神经传导（包含疼痛的传导）过程中的重要作用。在慢性疼痛的关节周围，神经生长因子（Nerve Growth Factor，NGF）浓度异常升高，促使机体释放P物质等引发一系列神经源性炎症，最终诱发疼痛。神经生长因子（NGF）是一种重要的致痛物质，可通过促进外周炎症反应、伤害感受器敏化、异位放电、交感神经芽生及中枢敏化参与神经病理性疼痛的发生和维持，NGF及其受体已成为临床镇痛药物开发的重要靶点。抑制NGF及其受体可有效缓解神经病理性疼痛。基于NGF及其受体的镇痛药物主要是通过阻断NGF、拮抗TrkA 受体和（或）p75 受体、抑制胞内TrkA激酶活性及NGF/TrkA 下游通路等策略开发相关药物。其中NGF抑制剂的研究热度相对更高。目前，NGF抑制剂领域主要分为两个主要方向，一者是人源化NGF单克隆抗体，由于其促神经分化的作用，镇痛剂量的NGF抗体不会引起认知功能的下降，对神经系统无显著的副作用，但临床试验却发现了神经病变和破坏性关节病等副作用可能，且与剂量、用药时间正相关；另一个则是NGF小分子抑制剂，但研究进度相对靠后，多处于临床前阶段。药品名称靶点适应症方向原研单位全球最高阶段管线状态法司努单抗 FasinumabNGF腰痛;骨关节炎;骨关节炎疼痛再生元制药临床Ⅲ期活跃伏雷努单抗 FulranumabNGF;NGFR癌性疼痛;神经痛；腰痛;膀胱疼痛;骨关节炎疼痛等安进临床Ⅲ期/他奈珠单抗 TanezumabNGF;NGFR慢性疼痛;癌性疼痛;神经痛;腰痛;膀胱疼痛;骨痛;骨转移疼痛礼来；辉瑞临床Ⅲ期/LEVI-04BDNF;NGFR;NT-3;NT-4骨关节炎疼痛Levicept Ltd;辉瑞临床Ⅱ期活跃EP-9001ANGF骨转移疼痛苑东生物临床Ⅱ期活跃DS002NGF;NGFR疼痛达石药业临床Ⅱ期活跃MEDI-7352NGFR慢性疼痛;糖尿病性神经性疼痛;骨关节炎疼痛阿斯利康临床Ⅱ期/ABT-110NGF疼痛;腰痛;骨关节炎疼痛PanGenetics BV;雅培临床Ⅱ期/SSS40NGF癌性疼痛;骨转移疼痛三生制药临床Ⅰ期活跃TNM009NGF关节痛;慢性疼痛;疼痛;癌性疼痛;骨关节炎疼痛;骨转移疼痛泰诺麦博制药临床Ⅰ期活跃AK-115NGF疼痛康方生物临床Ⅰ期/MEDI-578NGFR骨关节炎疼痛Medimmune LLC临床Ⅰ期/AMG-819NGF疼痛安进临床Ⅰ期/数据来源：药智数据数据显示，目前全球共有13款用于疼痛管理的单抗进入临床阶段，但其中活跃管线占比不足50%，NGF治疗开发层面全球制药企业屡屡受挫。辉瑞/礼来合作开发的Tanezumab作为最早进入临床的NGF抗体药物，但由于其安全性问题（包括OA快速进展和全膝关节置换术需求增加）其上市之路数度受阻。再生元的Fasinumab也因安全性问题，被FDA叫停了临床试验。强生、阿斯利康、安进也纷纷布局NGF抗体项目开发，却也举步维艰。目前来看，在NGF单抗用于关节疼痛治疗层面，制约其发展的主要原因在于关节止痛后的关节置换风险，据多项数据显示，LEVI-04有望解决NGF药物的上述安全性问题，其在拥有相当的镇痛效果(WOMAC疼痛评分平均降幅大于50%)的同时，不会导致骨关节炎快速进展，甚至还能维持神经营养因子稳态，利于维持软骨和骨修复。作为疼痛管理领域最具希望的下一代镇痛药物靶点之一，领域内后来者的热情非凡，尤其是国内相关Biotech企业，目前已知的就有苑东生物的EP-9001A、达石药业的DS002、三生制药的SSS40、泰诺麦博的TNM009。当然，除了上述NaV1.8抑制剂、NGF抑制剂与TRPV1抑制剂外，当今非阿片类止痛药研发领域还有不少值得重点注意的新药领域，比如WNT信号通路阻滞剂、ATR2拮抗剂、选择性CCR2拮抗剂、α2肾上腺素受体激动剂、内源性大麻素下的FAAH、NMDAR受体拮抗剂、NTRK1抑制剂等。每个细分领域都有着一份独属于自身的发展历程，虽然如今表面上NaV1.8抑制剂似乎在新机制止痛药层面已然拔得头筹，不过未来谁敢保证上述细分领域就不会迎来爆发？小结总结来看，疼痛管理的爆发逻辑已清晰可见：‌庞大患者基数‌、‌长周期用药属性叠加强大的支付意愿，使其市场黏性媲美减重赛道，加之现有药物（阿片类成瘾、非甾体药效弱）存在明显‌临床局限性与未满足需求，千亿替代空间，怎能不让人异常兴奋。而事实上，过去20年，疼痛管理新药研发屡屡碰壁，MNC药企无一不在该领域栽过跟头，但2025年Nav1.8抑制剂‌VX-548的获批却给行业注入一剂强心针，也让非阿片止痛药市场成为新的市场热点。展望未来，随着靶点迭代能力持续加强（从第一代到第三代Nav1.8抑制剂）、适应症差异化布局（聚焦口服制剂，专注癌痛、慢性痛）等竞争要素的细分。更关键的是，国内药企在疼痛管理新药研发层面投入强劲，尽管短期来看，在各细分领域均无任何一款新药占据头部优势，但如恒瑞、海思科与一众Biotech企业仍有望给行业带来新的惊喜。可以预见，疼痛管理新药市场，即将迎来百年时代变革，这场从精准机制打破阿片依赖的变革，或将重塑人类对抗疼痛的终极范式。来源 | 博药（药智网获取授权转载）撰稿 | 博药内容中心责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。合作、投稿 | 马老师 18323856316（同微信）阅读原文，是受欢迎的文章哦

上市批准临床研究

2024-10-22

·PipelineReview

First participants enrolled in first-in-human Phase I clinical trial with nociceptin (NOP) receptor agonist

AACHEN, Germany I October 22, 2024 I Today, Grünenthal announced that the first participants have been enrolled in a first-in-human Phase I clinical trial for a nociceptin (NOP) receptor agonist. The trial will include 90 healthy volunteers and aims to demonstrate a favourable safety and tolerability profile and to confirm the pharmacokinetic characteristics of the compound after single and multiple ascending doses. The results of the trial are expected in Q3 2025. “Grünenthal pioneered the research into NOP receptor agonists to deliver a unique and transformative first-in-class therapy option to millions of patients suffering from chronic pain,” says Gillian Burgess, Head of Research, Grünenthal. “With a unique mechanism of action for treating chronic pain, these molecules have the potential to deliver robust pain relief combined with an improved safety profile compared to the available standard of care.” Pre-clinical data show that NOP receptor agonists have the potential to act as potent analgesics without abuse liability. 1 Leveraging the clinical data Grünenthal obtained during the development of its NOP receptor programme, Grünenthal now brings forward a candidate that shows best-in-class potency and selectivity for the NOP receptor. These properties are predicted to provide robust pain relief in a broad range of chronic pain indications without the serious central nervous system related side effects associated with available opioids. Grünenthal’s R&D pipeline includes multiple programmes across different stages, targets, modalities, and mechanisms of action to deliver innovative treatment options for patients suffering from pain and related diseases. Recently, a Phase I clinical trial with a Glucocorticoid Receptor Modulator (GRM) has been completed. The compound is developed to provide patients with a therapy option for chronic inflammatory diseases. In addition, Grünenthal is running a Phase III clinical trial with Qutenza ® (capsaicin) 8% topical system in post-surgical neuropathic pain, aiming to expand its label in the United States. A global Phase III programme investigating the efficacy, safety and tolerability of Resiniferatoxin in patients with painful osteoarthritis of the knee is currently ongoing. About the NOP Receptor The nociceptin (NOP) receptor is a G protein-coupled receptor whose natural ligand is the 17 amino acid neuropeptide known as nociceptin (N/OFQ). 2 NOP Receptor agonists have been shown to act as potent analgesics without abuse liability in pre-clinical models. 1 Although the NOP Receptor shares some sequence identity (~60%) with the opioid receptors μ-OP (MOP), κ-OP (KOP), and δ-OP (DOP), they possess little or no affinity for opioid peptides or morphine-like compounds. Likewise, opioid receptors possess little affinity towards NOP’s endogenous ligand nociceptin. 3 About Grünenthal Grünenthal is a global leader in pain management and related diseases. As a science-based, fully integrated pharmaceutical company, we have a long track record of bringing innovative treatments and state-of-the-art technologies to patients worldwide. Our purpose is to change lives for the better – and innovation is our passion. We are focusing all our activities and efforts on working towards our vision of a World Free of Pain. Grünenthal is headquartered in Aachen, Germany, and has affiliates in 27 countries across Europe, Latin America, and the U.S. Our products are available in approx. 100 countries. In 2023, Grünenthal employed around 4,400 people and achieved revenues of €1.8 billion. More information: https://www.grunenthal.com Follow us on: LinkedIn: Grunenthal Group Instagram: grunenthal 1 Lin AP, Ko MC. The therapeutic potential of nociceptin/orphanin FQ receptor agonists as analgesics without abuse liability. ACS Chem Neurosci. 2013 Feb 20;4(2):214-24. doi: 10.1021/cn300124f. Epub 2012 Nov 6. PMID: 23421672; PMCID: PMC3582300. 2 Henderson G, McKnight AT (August 1997). “The orphan opioid receptor and its endogenous ligand– nociceptin/orphanin FQ”. Trends in Pharmacological Sciences. 18 (8): 293–300. doi:10.1016/S0165- 6147(97)90645-3. PMID 9277133. 3 Butour JL, Moisand C, Mazarguil H, Mollereau C, Meunier JC (February 1997). “Recognition and activation of the opioid receptor-like ORL 1 receptor by nociceptin, nociceptin analogs and opioids”. European Journal of Pharmacology. 321 (1): 97–103. doi:10.1016/S0014-2999(96)00919-3. PMID 9083791. SOURCE: Grünenthal Group

临床1期临床3期临床2期

100 项与树胶脂毒素相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
-	树胶脂毒素	-	DB06515

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
疼痛	临床3期	日本	Grünenthal GmbH	2022-08-26
疼痛	临床3期	加拿大	Grünenthal GmbH	2022-08-26
疼痛	临床3期	捷克	Grünenthal GmbH	2022-08-26
疼痛	临床3期	法国	Grünenthal GmbH	2022-08-26
疼痛	临床3期	德国	Grünenthal GmbH	2022-08-26
疼痛	临床3期	意大利	Grünenthal GmbH	2022-08-26
疼痛	临床3期	墨西哥	Grünenthal GmbH	2022-08-26
疼痛	临床3期	荷兰	Grünenthal GmbH	2022-08-26
疼痛	临床3期	波兰	Grünenthal GmbH	2022-08-26
关节炎疼痛	临床3期	美国	NovaQuest Capital Management LLC	2022-01-30

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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


NCT04885972 (EULAR 12024 \| EULAR 22024) 人工标引	临床2期	膝关节炎	67	RTX-GRT7039 0.5 mg	膚憲鑰壓顧簾範鹽鬱繭(糧艱遞選繭醖醖膚鑰遞) = 構積襯遞遞網簾積壓構鹹鏇鑰夢繭繭齋網蓋構 (淵窪簾壓繭鹽遞簾範鹽, 19.79) 更多	积极	2024-06-14
				RTX-GRT7039 2 mg	膚憲鑰壓顧簾範鹽鬱繭(糧艱遞選繭醖醖膚鑰遞) = 製夢繭衊顧選遞壓鏇範鹹鏇鑰夢繭繭齋網蓋構 (淵窪簾壓繭鹽遞簾範鹽, 34.16) 更多
ASN2021	N/A	抗中性粒细胞胞质抗体相关性血管炎维持 ANCA level	62	Rituximab (RTX)	簾積願範觸淵憲淵選壓(齋襯艱蓋製簾繭齋簾繭) = 築構夢鹹鹹構願鹽衊鹹簾顧壓廠鬱膚餘醖網製 (觸齋憲構顧襯積鑰築積 )	积极	2021-10-27
				Rituximab-Cyclophosphamide (RTX-CYC)	簾積願範觸淵憲淵選壓(齋襯艱蓋製簾繭齋簾繭) = 糧淵廠醖醖醖繭廠糧糧簾顧壓廠鬱膚餘醖網製 (觸齋憲構顧襯積鑰築積 )
ERA2019	N/A	肾病综合征 IgG level	107	Rituximab (RTX)	窪積範選艱餘獵簾簾衊(鹽鏇鬱餘鬱襯願顧鹽鹹) = Hypogammaglobulinemia is a frequent complication of RTX treatment in younger children treated for SDNS. The use of RTX in children younger than 8 years has to be carefully evaluated and their clinical and biological follow up should be adapted to the increased risk profil for hypogammaglobulinemia 繭廠願鹹襯繭選憲膚觸 (襯鏇淵蓋淵簾積獵廠夢 )	不佳	2019-06-13
SFN2004	N/A	心痛	-	Resiniferatoxin (RTX)	鹽簾築簾獵範廠壓鏇膚(窪憲憲鏇獵築廠鏇選選) = 糧廠餘廠製糧醖醖壓願淵襯範淵願鹹製蓋膚餘 (製觸餘鬱積範衊齋醖鬱 )	-	2004-10-24
				Vehicle	鹽簾築簾獵範廠壓鏇膚(窪憲憲鏇獵築廠鏇選選) = 鹽鹽窪願簾願製淵衊網淵襯範淵願鹹製蓋膚餘 (製觸餘鬱積範衊齋醖鬱 )