更新于：2024-11-11

Celecoxib

塞来昔布

更新于：2024-11-11

概要

概要

基本信息

简介CELEBREX是一种非甾体抗炎药。Celecoxib具有镇痛，抗炎和退热作用。CELEBREX的作用机制被认为是通过抑制前列腺素合成，主要通过抑制COX-2而实现的。Celecoxib是体外前列腺素合成的强效抑制剂。治疗期间达到的Celecoxib浓度已经产生了体内效果。前列腺素使传入神经末梢变得敏感，并增强了缓激肽诱导动物模型疼痛的作用。前列腺素是炎症介质。由于Celecoxib是前列腺素合成的抑制剂，因此其作用机制可能是通过减少外周组织中的前列腺素而实现的。CELEBREX适用于骨关节炎（OA），类风湿性关节炎（RA），少年类风湿性关节炎（JRA），强直性脊柱炎（AS），急性疼痛，原发性痛经。它最初由辉瑞公司在1998年在美国上市，用于治疗关节炎。

药物类型

小分子化药

别名

Celecoxib (JAN/USP/INN)、p-(5-p-Tolyl-3-(trifluoromethyl)pyrazol-1-yl)benzenesulfonamide、AD-2111

+ [22]

靶点

COX-2

作用机制

COX-2抑制剂(环氧化酶-2抑制剂)

治疗领域

肿瘤免疫系统疾病感染+ [7]

在研适应症

偏头痛疼痛牙痛+ [18]

非在研适应症

光化性角化病食管腺癌前列腺腺癌+ [37]

原研机构

Pfizer Inc.

在研机构

Scilex Pharmaceuticals, Inc.Viatris Pharmaceuticals LLC

Astellas Pharma, Inc.

+ [6]

非在研机构

Pfizer Inc.

Viatris, Inc.Dr. Reddy's Laboratories Ltd. (Russia)

+ [10]

最高研发阶段批准上市

首次获批日期

美国 (1998-12-31),

骨关节炎类风湿关节炎

最高研发阶段(中国)批准上市

特殊审评加速批准 (美国)、孤儿药 (美国)、优先审评 (中国)

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结构

分子式C17H14F3N3O2S

InChIKeyRZEKVGVHFLEQIL-UHFFFAOYSA-N

CAS号169590-42-5

关联

692

项与塞来昔布相关的临床试验

IRCT20200306046708N1 / Suspended临床2/3期IIT

Celecoxib added to mood stabilizer for treating acute mania: A randomized, double-blind, placebo-controlled trial

开始日期2633-12-15

申办/合作机构

Mashhad University of Medical Sciences

NCT03590821 / Not yet recruiting早期临床1期IIT

Modulating Celecoxib Induced Blood Pressure Changes by Timed Administration of Aspirin and the Human Chronobiome

To determine whether timed administration of aspirin ameliorates the effects of celecoxib on blood pressure.

开始日期2026-12-01

申办/合作机构

University of Pennsylvania

NCT04860635 / Suspended临床2/3期

An Open Label Safety Study of a Single Administration of F14 in Patients Undergoing Unilateral Total Knee Replacement

Open-label single-arm study in which all subjects receive F14 as part of a scheduled TKR and multimodal analgesia

开始日期2025-01-01

申办/合作机构

Arthritis Innovation Corp.

100 项与塞来昔布相关的临床结果

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100 项与塞来昔布相关的转化医学

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100 项与塞来昔布相关的专利（医药）

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7,555

项与塞来昔布相关的文献（医药）

2025-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Efficacy and safety of SKCPT in patients with knee osteoarthritis: A multicenter, randomized, double-blinded, active-controlled phase III clinical trial

Article

作者: In, Yong ; Bin, Sung Il ; Bin, Sung Ii ; Lee, Myung Chul ; Kim, Young-Mo ; Sim, Jae-Ang ; Seon, Jong-Keun ; Lee, Sang Jin ; Han, Seung-Beom ; Bae, Ki-Cheor ; Moon, Young-Wan ; Yoon, Kyoung Ho ; Kang, Seung-Baik ; Park, Kwan Kyu ; Chang, Chong Bum

ETHNOPHARMACOLOGICAL RELEVANCE:

Osteoarthritis (OA) is the most prevalent type of arthritis worldwide and a leading cause of years lost to pain and disability. Among the current pharmacological treatments for OA, symptomatic slow-acting drugs for OA (SYSADOA) induce pain relief and aim to improve joint function by relieving inflammation while causing fewer gastrointestinal and cardiovascular adverse events than non-steroidal anti-inflammatory drugs (NSAIDs). SKCPT is a herbal SYSADOA formulated from Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris powdered extracts. This preparation has been shown to induce cartilage protection and anti-inflammatory effects in preclinical studies and inhibit glycosaminoglycan degradation and catabolic gene expression in human OA chondrocytes and cartilage.

AIM OF THE STUDY:

We aimed to evaluate the non-inferiority of SKCPT to celecoxib and safety for treating knee OA.

MATERIALS AND METHODS:

This multicenter, randomized, double-blind, phase III clinical trial enrolled adults with primary knee OA who were randomized (1:1) to SKCPT 300 mg twice daily or celecoxib 200 mg once daily for 12 weeks.

RESULTS:

In total, 278 patients were assigned to treatment (SKCPT, 136; celecoxib, 142) for approximately 12 weeks. The primary endpoint was the mean change of Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) pain subscale scores from baseline to Day 84. The mean change (least squares [LS] mean ± standard error) from baseline to Day 84 was -23.74 ± 1.48 for SKCPT and -25.88 ± 1.44 for celecoxib. The two-sided 95% confidence interval of the difference (LS mean) between groups was [-1.94, 6.20], confirming that the upper limit was less than the non-inferiority margin of 10. Additionally, there were no significant differences in the secondary endpoints (mean changes of K-WOMAC pain, physical, stiffness subscale, and total score, and the frequency and number of doses of rescue medications) between groups at all time points. Differences between groups in adverse events and adverse drug reactions were not significant, and no serious adverse events occurred.

CONCLUSIONS:

SKCPT efficacy was non-inferior, and its safety profile was similar, to celecoxib. Building on previous results showing that SYSADOA reduce NSAID intake, the present results suggest that the SYSADOA SKCPT could effectively replace NSAIDs in knee OA treatment while avoiding long-term side effects.

2025-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Screening bioactive compounds from Fangji Huangqi decoction for treating rheumatoid arthritis via COX-2 magnetic ligand fishing combined with in vivo validation

Article

作者: Pan, Dongmei ; Yu, Qianqian ; Li, Ping ; Duan, Ao ; Zhu, Yongyan ; Tian, Shuo ; Tao, Huaming ; Zhu, Quanhong ; Zhou, Zishan

ETHNOPHARMACOLOGICAL RELEVANCE:

Fangji Huangqi Decoction (FHD) is a classical Chinese compound formula for treating rheumatoid arthritis (RA) with satisfactory effects. FHD is reputed for its ability to tonify qi with strengthening exterior, and dispel wind while removing dampness, but its mechanisms and bioactive compounds for treating RA remain unclear.

AIM OF THE STUDY:

The aim of this study was to explore the key target and bioactive compounds that were responsible for FHD-mediated improvements in RA.

MATERIALS AND METHODS:

Using network pharmacology, we discovered that cyclooxygenase-2 (COX-2) was the key target of FHD against RA. We utilized a ligand fishing technique with COX-2 immobilized magnetic beads to recognize the bioactive components that act on COX-2. Then we carried out an in vitro assay of COX-2 enzyme inhibition and in vivo assay of carrageenan-induced inflammation and collagen-induced arthritis (CIA) to validate the bioactive effects of these captured ingredients. In the CIA assay, micro-CT, hematoxylin‒eosin staining and safranin-O/fast green staining were employed to assess the influence of the captured ligand on bone damage, pathological injury and cartilage destruction, respectively. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assays (ELISAs) were used to detect the expression of COX-2 target in the ankle joint. interleukin-6 (IL-6) levels in the serum were also detected by ELISA. Molecular docking was used to reveal the binding mechanism of the COX-2 protein and the captured ligand.

RESULTS:

Eleven ligands, including tetrandrine, fangchinoline, cyclanoline, licochalcone B, ononin, calycosin and liquiritin, were specifically bound to the COX-2 protein, as determined by ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS), seven of which were present at high levels. One ligand, tetrandrine, not only had a great inhibitory effect on COX-2 enzyme activity but also significantly reduced carrageenan-induced inflammation. In the CIA assay, middle- and high-dose tetrandrine (25 and 50 mg/kg) had effects comparable to those of FHD and celecoxib on ameliorating RA symptoms in CIA mice via the COX-2 target. Furthermore, compared with the low-dose tetrandrine group (12.5 mg/kg), the FHD group exhibited significantly lower arthritis index scores and serum IL-6 expression, although the content of tetrandrine in FHD extract solution was approximately 0.1% of that in the low-dose tetrandrine group.

CONCLUSIONS:

Hence, we inferred that tetrandrine was the main bioactive component responsible for the effects of FHD against RA by suppressing the expression of the COX-2 protein and inhibiting the enzyme catalytic activity of COX-2. The reason for these effects may be that tetrandrine can interact with the residue Tyr385 of COX-2, the enzymatic catalytic site of COX-2 to transform arachidonic acid (AA) to prostaglandin E2 (PGE2), and thereby reduce the production of prostaglandins and inflammatory metabolites. Moreover, in addition to tetrandrine, FHD contains other compounds that could supplement the activity of tetrandrine when FHD was used to treat RA, which is manifested the "multi-component" characteristic of how Traditional Chinese Medicine formulas treat diseases.

2025-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Yiqi Yangxue formula inhibits cartilage degeneration in knee osteoarthritis by regulating LncRNA-UFC1/miR-34a/MMP-13 axis

Article

作者: Wang, Xinchang ; Qin, Dongdong ; Li, Zhaofu ; Zhao, Ting

ETHNOPHARMACOLOGICAL RELEVANCE:

Knee osteoarthritis (KOA) is a prevalent and disabling clinical condition affecting joint structures worldwide. The Yiqi Yangxue formula (YQYXF) is frequently prescribed in clinical settings for the treatment of KOA. Existing research has primarily focused on alterations in drug metabolism, with limited investigation into the epigenetic effects of YQYXF, particularly in relation to non-coding RNA.

AIM OF THE STUDY:

Exploring the effects of YQYXF on critical factors of long chain non-coding RNA UFC1/miR-34a/matrix metalloproteinase-13 (MMP-13) axis and their interrelationships.

METHODS:

UHPLC-QE-MS technology was used to identify the YQYXF ingredients in rat serum. KEGG and GO analysis were performed on the targets of blood components acting on KOA using a database. Simultaneously, a protein interaction network was constructed using target proteins and metabolites to identify the core components and key pathways of YQYXF. The KOA rat model was established using an improved Hulth method. SPF SD rats were randomly divided into normal group, sham surgery group, model group, celecoxib capsules group (18 mg/kg), YQYXF low, medium and high dose groups (4.6 g/kg, 9.2 g/kg, 18.4 g/kg). Observe the synovial and cartilage tissues of rats using pathological methods. RT-PCR was used to detect the levels of UFC1, miR-34a, and MMP-13 in cartilage. Immunohistochemistry was used to detect the levels of MMP-13 and ADAMTS-5 in cartilage. ELISA method was used to detect the levels of MMP-13 and ADAMTS-5 in serum. In addition, we further validated the regulation of crucial factor expression levels of UFC1/miR-34a/MMP-13 axis in rat chondrocytes and degenerative chondrocytes of KOA patients by YQYXF, providing a basis for its treatment of KOA.

RESULTS:

The compounds that YQYXF enters the bloodstream mainly contain flavonoids and phenylpropanoid compounds. The core components that act on OA include quercetin, fisetin, and demethylweldelolactone. The main target pathways are the IL-17 signaling pathway, lipid and atherosclerosis, cellular sensitivity, inflammatory mediator regulation of TRP channels, TNF signaling pathway, relaxin signaling pathway and C-type lectin receptor signaling pathway. YQYXF inhibited the expression of miR-34a and MMP-13 mRNA, and reduced the protein levels of MMP-13 and ADAMTS-5. In vitro studies have confirmed that 20% YQYXF serum promoted UFC1 and reduce miR-34a levels. In addition, miR-34a in sh-UFC1+10% YQYXF serum and sh-UFC1+20% YQYXF serum groups significantly decreased compared to the sh-UFC1 group.

CONCLUSION:

The anti-KOA cartilage degeneration effect of YQYXF might be related to inhibiting cell apoptosis and promoting cell proliferation, which regulated the lncRNA-UFC1/miR-34a/MMP-13 axis.

370

项与塞来昔布相关的新闻（医药）

2024-11-10

·肿瘤界

家族性腺瘤性息肉病的化学预防药物进展与展望

点击蓝字关注我们引用本文：卢丽婷，王晰程，巴一．家族性腺瘤性息肉病的化学预防药物进展与展望[J/CD]．肿瘤综合治疗电子杂志，2024，10（4）：101- 108．通信作者：王晰程 E-mail：xicheng_wang2024@163.com 家族性腺瘤性息肉病（familial adenomatous polyposis，FAP）是一种由APC基因胚系突变引起的常染色体显性遗传病，APC基因突变位置与结肠息肉病的发病年龄、严重程度、癌症风险等级及有无结肠外表现密切相关[1-2]。经典型FAP大多与发生在密码子169～1 393之间的突变相关，通常在青少年时期即出现数百甚至数千个结直肠腺瘤样息肉，未经治疗的患者会进一步发展为结直肠癌[3-4]。FAP患者也可能表现出多种结直肠外症状，如硬纤维瘤、十二指肠腺瘤、骨瘤、先天性视网膜色素上皮肥大、甲状腺癌、肝胆胰及上消化道恶性肿瘤等[5]。鉴于高发结直肠癌风险，2020年美国胃肠内镜学会指南推荐患者从10～12岁进行内镜下监测及息肉切除[6]。但内镜监测间隔期内仍有癌症发生的风险。目前，根据患者的腺瘤负荷和个人偏好，预防性手术如全结肠切除术＋回肠直肠吻合术（ileoanal anastomosis，IRA）或全结肠直肠切除术＋回肠储袋肛管吻合术（ileal pouch-anal anastomosis，IPAA）是标准治疗方案。与IRA相比，尽管IPAA降低了残余直肠癌变的风险，但二者均不能完全消除FAP相关肠外肿瘤发生风险，且2种术式患者术后肠功能障碍和硬纤维瘤发生率相当[7-9]。因此患者需终身进行内镜监测和进一步干预，严重影响生活质量。化学预防旨在通过药物减少息肉数量和大小，从而延迟或避免手术，减少内镜检查和息肉切除的频率，降低手术相关并发症发生率，并防止癌症的进展。对于息肉负担尚未严重到需要进行结肠切除的青少年患者，化学预防可以减轻患者的心理和生理负担，使其达到更成熟的决策年龄[10]。此外，硬纤维瘤是FAP的第二大死因，与手术、创伤及雌激素相关[11-12]。对于APC基因突变位点更易发生硬纤维瘤的患者，通过化学预防延迟甚至避免手术有利于患者的生存[13]。更长时间的术前监测也有助于更清楚地了解腺瘤负荷，制订更好的个性化治疗方案。目前关于FAP的化学预防的探索已有40余年，但FAP的化学预防还处于早期阶段，尚无药物被批准。本文旨在对FAP化学预防的现有文献及研究进展作一综述，以期对其有全面了解并为未来开展临床试验提供方向。 1. 非甾体抗炎药非甾体抗炎药（nonsteroidal anti-inflammatory drugs，NSAIDs）通过抑制环氧合酶（cyclooxygenase，COX），尤其是COX-2，减少前列腺素的合成，具有抗炎、镇痛和解热作用。COX-2的过表达与结直肠癌的增殖、侵袭、血管生成及抗凋亡等过程密切相关[14]。NSAIDs能抑制COX-2活性，减少前列腺素E2的生成，抑制息肉增生和血管生成，诱导癌细胞凋亡，影响Wnt/β-catenin信号通路。此外，COX-2的异常表达与APC基因突变相互影响[15]，表明COX抑制剂可能对FAP患者具有预防作用，其安全性和有效性已在临床试验中得到探究。 1.1 舒林酸舒林酸是一种非选择性NSAIDs，可竞争性抑制COX-1和COX-2，是最早用于FAP化学预防研究的药物之一。1991年，Labayle等[16]的研究显示，在10例先前接受过结肠切除术的FAP患者中，服用舒林酸组（300 mg/d）与安慰剂组相比，息肉消退率比较差异有统计学意义（P＜ 0.01）。后续研究显示，舒林酸能显著减少未接受手术FAP患者的息肉数量和直径，但一旦停药，患者息肉数量、直径均增加[17]。低剂量舒林酸栓剂（50 mg/d）连续治疗33个月可使87%的直肠息肉患者腺瘤逆转，且安全性良好[18]。多项研究均表明，舒林酸治疗有效性不受APC基因突变位点影响，且对十二指肠息肉也有效果，但对壶腹周围息肉无效[19-20]。一项针对8～25岁APC突变携带者的研究结果显示，尽管舒林酸组黏膜前列腺素水平低于安慰剂组，但息肉直径和数量的获益无统计学意义[21]。此外，尽管在舒林酸治疗中进行密切内镜随访，但仍有患者进展为结直肠癌。这些研究均为小样本研究，且多数患者仅评估了直肠病变，其能否转变为临床获益尚需进一步研究证实。舒林酸的代谢产物显示出一定的抑制肿瘤的潜力，但在一项研究中，6个月治疗后对息肉数量无显著影响，且因其肝脏毒性也限制了剂量增加[22]。 1.2 阿司匹林阿司匹林作为广泛应用的非选择性NSAIDs，美国胃肠病学会指南建议50～69岁有心血管疾病风险的人群使用低剂量阿司匹林以降低结直肠癌和心血管疾病风险[23]。CAPP1研究纳入了206例10～21岁的FAP患者，发现阿司匹林片联合抗性淀粉组中位治疗17个月后，与安慰剂组相比，息肉负荷有减小趋势，差异无统计学意义，但阿司匹林组在用药超过1年后最大息肉直径显著减小（P＝0.02）[24]。日本一项研究[25]评估了阿司匹林（100 mg/d）与安慰剂的疗效，亚组分析显示，治疗前平均基线息肉直径为≤2 mm的受试者经阿司匹林干预后息肉直径和息肉数量均显著减少，但阿司匹林联合抗性淀粉组组有18%受试者出现严重不良反应。J-FAPP-Ⅳ研究[26]纳入104例患有超过100个大肠腺瘤性息肉且未接受结肠切除术的患者，在研究前，患者接受了内镜切除所有直径至少5 mm的结直肠息肉，结果显示，服用阿司匹林8个月的患者结肠息肉复发率显著降低，而美沙拉嗪组未见明显效果。但该研究入组患者中位年龄为30岁以上且无结直肠癌，可能为较轻表型，且阿司匹林仅给药8个月，长期使用的安全性仍是限制其广泛应用的主要问题。 1.3 塞来昔布鉴于非选择性NSAIDs的胃肠道不良反应，塞来昔布作为一种选择性COX-2抑制剂在FAP中的化学预防作用得到广泛关注。Steinbach等[27]的研究将77例18～65岁的FAP患者分为安慰剂组、低剂量塞来昔布组（100 mg，2次/d）和高剂量塞来昔布组（400 mg，2次/d），与安慰剂组相比，6个月内高剂量塞来昔布组患者结直肠息肉总数减少了28% （P＝0.003），息肉直径之和下降30.7%（P＝0.001），各组间不良事件发生率相似。而低剂量塞来昔布组相对于安慰剂组无显著差异。进一步分析显示，对于初始十二指肠黏膜受累超过5%的患者，服用塞来昔布（400 mg，2次/d）可将十二指肠受累面积减少31%[28]。另一项Ⅰ期剂量递增试验评估了短期塞来昔布治疗FAP患儿的安全性和有效性，塞来昔布（16 mg/kg，1次/d）对FAP患儿是安全且耐受良好的，安慰剂组受试者在第3个月时息肉数量增加了39.1%，而最高剂量塞来昔布组患者中，息肉数量减少了44.2%（P＝0.01）[29]。Burke等[30]进行的CHIP研究，将10～17岁的FAP患儿随机分配至塞来昔布组（16 mg/kg，1次/d）或安慰剂组，持续干预5年。结果显示，塞来昔布组患儿疾病进展（最早出现≥20个直径＞2 mm息肉）的中位时间为2.1年，安慰剂组患儿为1.1年，无患者发展成结肠直肠癌。由于观察到的终点率低，长期影响尚不明确。对于高剂量塞来昔布长期治疗的安全性（尤其是心血管事件风险）和效果，以及与其他药物联合使用的潜在协同效应，仍需进一步的研究来确认。 1.4 基于NSAIDs药物的组合疗法 1.4.1 联合依氟鸟氨酸多胺是一类含氨基的小分子代谢物，在细胞生长中发挥核心作用。在FAP患者中，多胺合成的关键酶鸟氨酸脱羧酶（ornithine decarboxylase，ODC）活性及黏膜多胺水平在正常和腺瘤组织中均显著升高[31]。依氟鸟氨酸是一种强效ODC抑制剂，在ApcMin/+小鼠中，依氟鸟氨酸联合NSAIDs可使肠道肿瘤数量减少超过80%（P＜0.000 1）；与单独使用舒林酸相比，其联合治疗可以显著减少高级别腺瘤的发生（P＝0.003）[32]。Ⅲ期临床试验评估了依氟鸟氨酸（750 mg/d）与舒林酸（150 mg/d）联合治疗与单药治疗在成人FAP患者的疗效和安全性[33]。该研究持续48个月，纳入171例患者，主要研究终点为疾病进展。结果显示，联合用药组并未显著降低疾病进展发生率[34]，但在延迟下消化道手术方面表现出显著优势（P＝0.02）[35]，但需要注意依氟鸟氨酸的耳毒性。另一项随机Ⅱ期试验显示，塞来昔布（400 mg，2次/d）联合或不联合依氟鸟氨酸在预防息肉病患者腺瘤方面无显著差异[36]。 1.4.2 联合厄洛替尼体细胞APC失活和表皮生长因子受体（epidermal growth factor receptor，EGFR）信号转导可促进COX-2表达和随后的腺瘤-癌发展[37]。厄洛替尼是一种抗EGFR活性的口服酪氨酸激酶抑制剂。FAPEST研究显示，舒林酸（150 mg，2次/d）联合厄洛替尼（75 mg/d）可在6个月后显著降低FAP患者结直肠及十二指肠息肉负荷[38-39]。但联合治疗可能引发痤疮样皮疹等不良反应，长期使用还与心脏毒性相关[38-40]。一项Ⅱ期单臂试验评估了厄洛替尼（350 mg，1次/周）干预能否有效降低息肉负荷并改善不良事件状况。结果表明，厄洛替尼干预6个月后，十二指肠息肉负荷显著减轻，平均百分比变化为-29.6%，12%的患者Spigelman评分降级，且整体不良事件可接受，但仍需更多数据证实其长期安全性[41]。 1.4.3 其他近年来研究表明，FAP患者的肠道菌群谱与正常人及腺瘤患者不同，致瘤菌群可能通过DNA损伤、慢性炎症等机制促进FAP进展[42]。一项舒林酸联合双歧杆菌三联活菌治疗FAP的临床试验表明，舒林酸联合双歧杆菌三联活菌组疗效优于单纯服用舒林酸组和双歧杆菌三联活菌组[43]。其原因可能与降低Bcl-2基因表达、减少对凋亡的抑制、改善肠内环境菌群等有关。以上研究表明，调节肠道菌群，维持肠道微生态平衡可能成为FAP预防的新途径。 2. 二十碳五烯酸二十碳五烯酸（eicosapentaenoic acid，EPA）是ω-3多不饱和脂肪酸的一种，属于人体必需脂肪酸，主要来源于鱼油。临床前研究显示，EPA可减缓结直肠腺瘤病史患者的隐窝细胞增殖，促进正常结肠黏膜的细胞凋亡[44]。其作用机制可能涉及作为COX-2的替代底物减少前列腺素E2生成，改变T淋巴细胞与结肠细胞膜的脂筏功能并调节信号转导，以及增强氧化应激以促进细胞凋亡[45]。在多中心、随机seAFOod试验[46]中，28例接受过结肠切除术的FAP患者接受EPA（2 g/d）治疗6个月后，息肉数量平均减少22.4%（P＝0.012），息肉直径总和平均减少29.8%（P＝0.027），与选择性COX-2抑制剂塞来昔布的效果相似。同时EPA耐受性良好，不良事件发生率与安慰剂相似。EPA在结直肠腺瘤治疗中显示出潜在效益，特别是在减缓息肉生长方面。 3. 西罗莫司西罗莫司是一种大环内酯类免疫抑制剂，仅抑制哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）C1的活性，不影响mTORC2。研究表明，西罗莫司可使ApcMin/+小鼠的肠道肿瘤细胞停止生长和分化，甚至可能导致息肉消退[47]。有病例报道了低剂量西罗莫司（0.05～0.1 mg/kg）在2例FAP患儿中的成功应用[48]。该病例治疗1年后，1例患儿显示壶腹周围息肉完全消退，结直肠息肉减小，黏膜发育异常程度降低；另1例患儿的结肠息肉负荷降低，但胃息肉负荷未发生变化，2例患儿均未出现严重不良反应。随后一项纳入5例FAP患者的前瞻性Ⅱ期临床试验显示，4例FAP患者接受西罗莫司治疗6个月后，直肠回肠袋息肉数量明显减少，但不良事件发生率高，1例患者因不能耐受中途退出试验[49]。考虑到西罗莫司的不良反应与血药浓度呈正相关，目前的ⅡA期试验使用封装西罗莫司，以更一致且更低剂量的药物探索其能否预防FAP患者的疾病进展（NCT04230499）。以上研究表明，西罗莫司及其衍生物在FAP化学预防中具有潜力，但其不良反应需要引起高度重视。 4. 二甲双胍 Meta分析显示，长期使用二甲双胍能够降低结直肠腺瘤及癌症风险[50]。Ⅲ期临床研究发现，对非糖尿病患者在息肉切除术后给予低剂量二甲双胍（250 mg/d）干预1年，可减少腺瘤或息肉复发[51]。然而，与一般人群的散发性腺瘤不同，FAP患者的腺瘤数量更多。一项纳入34例韩国FAP患者的随机研究表明，每日口服二甲双胍500 mg或1500 mg治疗7个月并未显著改变结直肠和十二指肠的总体息肉负荷[52]。我国学者发现，1年二甲双胍治疗FAP安全有效，与安慰组相比，试验组患者（每日口服250 mg二甲双胍）的息肉平均数和特定区域的平均息肉负荷显著减少（P＜0.05），且二甲双胍可能通过调节肠道菌群抑制FAP中腺瘤性息肉的发展[53]。在临床上，二甲双胍联合内镜检查被证实优于单独内镜检查治疗FAP。二甲双胍在非糖尿病患者中的应用显示了其在预防腺瘤复发方面的潜力，未来研究应在FAP患者中进一步探索调节肠道菌群与二甲双胍的联合作用，不同的膳食模式也可能对研究结果产生影响。 FAP化学预防随机对照试验汇总如表1所示。 5. 正在进行的试验 lorpucitinib（JNJ-64251330研究）是一种口服小分子泛Janus激酶（Janus kinase，JAK）抑制剂，可阻断信号转导和转录激活因子蛋白（signal transducer and activator of transcription，STAT）的磷酸化，从而抑制与炎症性疾病进展相关的基因转录。2023年美国临床肿瘤学会年度会议报告了lorpucitinib在FAP患者中的Ⅰb期研究（NCT05014360）结果，结果显示，lorpucitinib在FAP患者中表现出肠道选择性分布，虽然息肉负荷的减少在临床上并不显著，但lorpucitinib降低了几种血清炎症生物标志物的水平，有助于改善FAP相关的临床症状，且其具有良好的安全性和耐受性[54]。 REC-4881是一种人工智能辅助开发的口服MEK1和MEK2的非ATP竞争性的小分子别构抑制剂。据推测，REC-4881可能是通过抑制FAP腺瘤中异常的丝裂原激活蛋白激酶（mitogen activation protein kinase，MAPK）信号转导而使肿瘤消退或减慢其生长。目前，一项多中心的评估其在FAP患者中的疗效和安全性的Ⅰb～Ⅱ期试验正在进行（NCT 05552755）。奥贝胆酸是一种经美国食品药品监督管理局批准用于治疗原发性胆汁性胆管炎的选择性胆汁酸受体激动剂，已显示出减轻炎症和纤维化的潜力[55]。一项Ⅱa期安慰剂对照随机研究正在招募，旨在评估奥贝胆酸干预6个月对FAP患者肠息肉负荷的影响（NCT05223036）。锂在apcMin/+小鼠中显示出抑制肠干细胞扩增的作用，尽管尚无锂在FAP患者中的应用报道，但已有研究表明，其可降低双相情感障碍患者的结直肠癌和其他癌症发病率[56]。一项前瞻性Ⅱ期单臂试验正在探讨低剂量锂对FAP患者的干细胞动力学、息肉数量和大小的影响（NCT05402891）。白细胞介素-23（interleukin-23，IL-23）通过激活JAK/STAT3通路维持结直肠癌进展的炎症特征已被证实[57]。一项针对FAP受试者的Ⅰb期临床研究评估靶向IL-23的guselkumab单抗的疗效已完成招募，结果尚未发布（NCT03649971研究）。 6. 总结与展望 FAP的治疗与预防是一项复杂的挑战，涉及基因、药物和肠道环境等多个层面。迄今为止，化学预防研究尚未在临床实践中常规使用，因为先前研究样本量有限且存在矛盾，同时常伴随不良事件。FAP主要与APC基因突变相关，不同的突变类型及位点对疾病表型有显著影响。精确的基因分型和全基因组测序对于实现个体化的风险评估和预防策略至关重要。此外，对于携带特定突变的患者，可以考虑更为针对性的药物干预，如针对特定突变的小分子抑制剂，以提高治疗的针对性和有效性。此外，肠道菌群的调节和特定炎症途径的药物干预也显示出预防FAP的潜力。未来研究需整合这些信息以优化治疗方案，实现个体化治疗，提高治疗的针对性和有效性。参考文献 [1] HEINEN C D. 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[22] VAN STOLK R, STONER G, HAYTON W L, et al. PhaseⅠ trial of exisulind (sulindac sulfone, FGN-1) as a chemopr ev-entive agent in patients with familial adenomatous polyposis[J]. Clin Cancer Res, 2000, 6(1):78-89. [23] SHAUKAT A, KAHI C J, BURKE C A, et al. ACG clinical guidelines: colorectal cancer screening 2021[J]. Am J Gastroe-nterol, 2021, 116(3):458-479. [24] BURN J, BISHOP D T, CHAPMAN P D, et al. A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis[J]. Cancer Prev Res (Phila), 2011, 4(5):655-665. [25] ISHIKAWA H, WAKABAYASHI K, SUZUKI S, et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial[J]. Cancer Med, 2013, 2(1):50-56. [26] ISHIKAWA H, MUTOH M, SATO Y, et al. Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study Ⅳ): a multicentre, double-blind, randomised, two-by-two factorial design trial[J]. Lancet Gastroenterol Hepatol, 2021, 6(6):474-481. [27] STEINBACH G, LYNCH P M, PHILLIPS R K, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis[J]. N Engl J Med, 2000, 342(26):1946- 1952. [28] PHILLIPS R K, WALLACE M H, LYNCH P M, et al. A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis[J]. Gut, 2002, 50(6):857-860. [29] LYNCH P M, AYERS G D, HAWK E, et al. The safety and efficacy of celecoxib in children with familial adenomatous polyposis[J]. Am J Gastroenterol, 2010, 105(6):1437-1443. [30] BURKE C A, PHILLIPS R, BERGER M F, et al. Children's International Polyposis (CHIP) study: a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis[J]. Clin Exp Gastroenterol, 2017, 10:177-185. [31] GIARDIELLO F M, HAMILTON S R, HYLIND L M, et al. Ornithine decarboxylase and polyamines in familial adenomatous polyposis[J]. Cancer Res, 1997, 57(2):199-201. [32] IGNATENKO N A, BESSELSEN D G, STRINGER D E, et al. Combination chemoprevention of intestinal carcinogenesis in a murine model of familial adenomatous polyposis[J]. Nutr Cancer, 2008, 60(Suppl 1):30-35. [33] BURKE C A, DEKKER E, SAMADDER N J, et al. Efficacy and safety of eflornithine (CPP-1X)/sulindac combination therapy versus each as monotherapy in patients with familial adenomatous polyposis (FAP): design and rationale of a randomized, double-blind, phase Ⅲ trial[J]. BMC Gastro-enterol, 2016, 16(1):87. [34] BURKE C A, DEKKER E, LYNCH P, et al. Eflornithine plus sulindac for prevention of progression in familial adenomatous polyposis[J]. N Engl J Med, 2020, 383(11):1028-1039. [35] BALAGUER F, STOFFEL E M, BURKE C A, et al. Combin-ation of sulindac and eflornithine delays the need for lower gastrointestinal surgery in patients with familial adenomatous polyposis: post hoc analysis of a randomized clinical trial[J]. Dis Colon Rectum, 2022, 65(4):536-545. [36] LYNCH P M, BURKE C A, PHILLIPS R, et al. An interna-tional randomised trial of celecoxib versus celecoxib plus difluor omethylornithine in patients with familial adenomatous polyposis[J]. Gut, 2016, 65(2):286-295. [37] ROBERTS R B, MIN L, WASHINGTON M K, et al. Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis[J]. Proc Natl Acad Sci U S A, 2002, 99(3):1521-1526. [38] SAMADDER N J, NEKLASON D W, BOUCHER K M, et al. Effect of sulindac and erlotinib vs placebo on duodenal neoplasia in familial adenomatous polyposis: a randomized clinical trial[J]. JAMA, 2016, 315(12):1266-1275. [39] SAMADDER N J, KUWADA S K, BOUCHER K M, et al. Association of sulindac and erlotinib vs placebo with colorectal neoplasia in familial adenomatous polyposis: secondary analysis of a randomized clinical trial[J]. JAMA Oncol, 2018, 4(5):671-677. [40] BAKER H. Sulindac plus erlotinib for familial adenomatous polyposis[J]. Lancet Oncol, 2016, 17(5):e183. [41] SAMADDER N J, FOSTER N, MCMURRAY R P, et al. Phase Ⅱ trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis[J]. Gut, 2023, 72(2):256-263. [42] DEJEA C M, FATHI P, CRAIG J M, et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria[J]. Science, 2018, 359(6375):592-597. [43] 杨翠萍，杨晓金，李婷等．舒林酸联合双歧杆菌三联活菌治疗家族性腺瘤性息肉病的作用及其机制初探[J/CD]．中华消化病与影像杂志（电子版），2022，12（5）：286-290． [44] COURTNEY E D, MATTHEWS S, FINLAYSON C, et al. Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas[J]. Int J Colorectal Dis, 2007, 22(7):765-776. [45] COCKBAIN A J, TOOGOOD G J, HULL M A. Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer[J]. Gut, 2012, 61(1):135-149. [46] WEST N J, CLARK S K, PHILLIPS R K, et al. Eicosapen-taenoic acid reduces rectal polyp number and size in familial adenomatous polyposis[J]. Gut, 2010, 59(7):918-925. [47] FALLER W J, JACKSON T J, KNIGHT J R, et al. mTORC1- mediated translational elongation limits intestinal tumour initiation and growth[J]. Nature, 2015, 517(7535):497-500. [48] YUKSEKKAYA H, YUCEL A, GUMUS M, et al. Familial adenomatous polyposis; succesful use of sirolimus[J]. Am J Gastroenterol, 2016, 111(7):1040-1041. [49] ROOS V H, MEIJER B J, KALLENBERG F G J, et al. Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study[J]. BMJ Open Gastroenterol, 2020, 7(1):e000497. [50] JUNG Y S, PARK C H, EUN C S, et al. Metformin use and the risk of colorectal adenoma: a systematic review and meta-analysis[J]. J Gastroenterol Hepatol, 2017, 32(5):957-965. [51] HIGURASHI T, HOSONO K, TAKAHASHI H, et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial[J]. Lancet Oncol, 2016, 17(4):475- 483. [52] PARK J J, KIM B C, HONG S P, et al. The effect of metformin in treatment of adenomas in patients with familial adenomatous polyposis[J]. Cancer Prev Res (Phila), 2021, 14(5):563-572. [53] ZHOU L, ZHENG L, XU B, et al. Clinical efficacy of metformin in familial adenomatous polyposis and the effect of intestinal flora[J]. Orphanet J Rare Dis, 2024, 19(1):88. [54] MA X, BORZILLO G, KOTHE M J C, et al. A phase Ⅰ, rando-mized, multi-dose study to evaluate the enteric selectivity and safety of jak inhibitor, lorpucitinib, in healthy participants[J]. Clin Pharmacol Ther, 2024, 115(5):1075-1084. [55] GULAMHUSEIN A F, HIRSCHFIELD G M. Primary biliary cholangitis: pathogenesis and therapeutic opportunities[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(2):93-110. [56] WILTING I, HEERDINK E R, MERSCH P P, et al. Association between lithium serum level, mood state, and patient-reported adverse drug reactions during long-term lithium treatment: a naturalistic follow-up study[J]. Bipolar Disord, 2009, 11(4): 434-440. [57] LANGOWSKI J L, ZHANG X, WU L, et al. IL-23 promotes tumour incidence and growth [J]. Nature, 2006, 442(7101):461- 465. 声明：本文由“肿瘤界”整理与汇编，欢迎分享转载，如需使用本文内容，请务必注明出处。排版：lagertha 校对：松月

临床结果临床研究

2024-11-07

·GlobeNewswire-Health Care

Dogwood Therapeutics Announces Third Quarter 2024 Financial Results

- Dogwood Therapeutics, Inc. (Nasdaq: “DWTX”) formed in October by combination of Virios Therapeutics, Inc. and Pharmagesic (Holdings) Inc., 100% parent company of Wex Pharmaceuticals, Inc. (the “Combination”) - - Expanded pipeline with multiple programs in large markets with high unmet need - - Strategic financing results in combined working capital of approximately $23 million to fund operations and advance Phase 2b Halneuron® development through 2025 - - Top-line results from Long-COVID Phase 2a study expected in mid-November 2024 - - NaV 1.7 inhibition pain treatment, Halneuron®, Phase 2b study for chemotherapy-induced neuropathic pain expected interim readout 2H 2025 - ATLANTA, Nov. 07, 2024 (GLOBE NEWSWIRE) -- Dogwood Therapeutics, Inc. (Nasdaq: DWTX) (the “Company”), a development-stage biotechnology company developing new medicines to treat pain and fatigue-related disorders, today announced financial results for the third quarter ended September 30, 2024 and provided a business update. “The formation of Dogwood Therapeutics last month represents a transformational expansion of our pipeline with the addition of Halneuron®, a non-opioid, novel NaV 1.7 modulator to treat neuropathic pain associated with chemotherapy, purposefully complementing our promising development assets IMC-1 and IMC-2,” said Greg Duncan, Chief Executive Officer of Dogwood Therapeutics. “The concurrent strategic financing to be provided by an affiliate of CK Life Sciences Int’l., (Holdings) Inc. (“CKLS”), former owner of Pharmagesic (Holdings) Inc., provides us with operating capital through 2025. We see this as a win-win for legacy Virios shareholders and CKLS, with both short-term and medium-term value creation opportunities associated with forthcoming data from the Bateman-Horne Center (“BHC”) managed IMC-2 Phase 2 Long-COVID trial, and the Halneuron® Phase 2b interim data projected for the second half of next year.” Key Highlights Dogwood’s expanded pipeline includes three late-stage assets: Halneuron®, currently in Phase 2b development for chemotherapy-induced neuropathic pain (“CINP”); IMC-1, poised for Phase 3 development as a treatment for fibromyalgia (“FM”); and IMC-2, currently in Phase 2 development to treat Long-COVID (“LC”) sequelae.In connection with the Combination, the Company announced that it raised $19.5 million in committed debt financing by an affiliate of CKLS in two tranches with $16.5 million funded as of October 7, 2024 and an additional $3.0 million to be funded in 1Q 2025, subject to certain conditions. This financing is expected to fund research and operations through several key milestones, including the release of results from the Halneuron® Phase 2b interim analysis assessment expected in 2H 2025.Top-line results from the ongoing BHC IMC-2 LC Phase 2a study, assessing two doses of the combination of valacyclovir + celecoxib versus placebo, are expected by mid-November 2024. Dogwood Therapeutics Proprietary Pipeline Includes: Halneuron® is in Phase 2b development as a non-opioid, NaV 1.7 inhibitor to treat the neuropathic pain associated with chemotherapy treatment. Halneuron® has been granted fast track designation from the Food and Drug Administration (“FDA”) for the treatment of CINP. Next milestone: Interim data from the ongoing Phase 2b CINP study are expected in 2H 2025. IMC-2 (valacyclovir + celecoxib) is in Phase 2a development as a combination antiviral treatment for LC. Next milestone: Topline data from an investigator led, double blind controlled proof of concept study, assessing two doses of IMC-2 vs placebo, are expected in mid-November 2024. IMC-1 (famciclovir + celecoxib) is ready for Phase 3 development as a combination antiviral treatment for FM. IMC-1 has been granted fast track designation by the FDA for the treatment of FM. Dogwood is exploring partnerships for IMC-1 to execute the Phase 3 FM program agreed upon by the FDA. Third Quarter 2024 Financial Results Research and development expenses increased by $0.2 million for the third quarter of 2024 compared to the third quarter of 2023. The quarter-over-quarter change was primarily due to increases in expenses associated with the grant to BHC for the second proof-of-concept study in LC of $0.3 million offset by a decrease in regulatory expenses of $0.1 million. General and administrative expenses increased by $0.9 million for the third quarter of 2024 compared to the third quarter of 2023. The quarter-over-quarter change was primarily due to higher legal and professional fees related to the business combination in October 2024 of $1.0 million offset by lower insurance expenses associated with being a public company of $0.1 million. Net loss for the third quarter of 2024 was $2.3 million, or $2.05 basic and diluted net loss per share, compared to a net loss of $1.2 million, or $1.62 basic and diluted net loss per share for the third quarter of 2023 (as adjusted to reflect the reverse stock split implemented on October 9, 2024). The Company estimates that its current cash of $2.0 million at September 30, 2024 along with the $16.5 million in loan proceeds received on October 7, 2024 is not sufficient to fund operating expenses and capital requirements for at least the next 12 months. The Company will need to secure the additional $3.0 million of loan proceeds available to us under the terms of the loan agreement in February 2025 to continue to fund our operations through 2025. About Dogwood Therapeutics Dogwood Therapeutics (Nasdaq: DWTX) is a development-stage biopharmaceutical company focused on developing new medicines to treat pain and fatigue-related disorders. The Dogwood research pipeline includes two separate mechanistic platforms with a non-opioid analgesic program and an antiviral program. The proprietary non-opioid, Nav 1.7 analgesic program is centered on lead development candidate, Halneuron® which is a voltage-gated sodium channel blocker, a mechanism known to be effective for reducing pain. Halneuron® treatment has demonstrated pain reduction of both general cancer related pain and CINP. Interim data from the forthcoming Phase 2 CINP study are expected in 2H 2025. The antiviral program includes IMC-1 and IMC-2, which are novel, proprietary, fixed dose combinations of nucleoside analog, anti-herpes antivirals and the anti-inflammatory agent, celecoxib, for the treatment of illnesses believed to be related to reactivation of previously dormant herpes viruses, including FM and LC. Top-line data from an ongoing IMC-2 Phase 2 LC study are expected in mid-November 2024. IMC-1 is poised to progress into Phase 3 development as a treatment for FM and is the focus of external partnership activities. For more information, please visit www.dwtx.com. Follow Dogwood Therapeutics Email Alerts: https://ir.dwtx.com/resources/email-alerts LinkedIn: https://www.linkedin.com/company/dogwoodther/ Twitter: https://twitter.com/dogwoodther Facebook: https://www.facebook.com/dogwoodther Forward-Looking Statements Statements in this press release contain “forward-looking statements,” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “suggest,” “target,” “aim,” “should,” "will,” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Dogwood’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including risks related to the completion, timing and results of current and future clinical studies relating to Dogwood’s product candidates. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled “Risk Factors” in the Amended Annual Report on Form 10-K/A for the year ended December 31, 2023 and the Company’s quarterly report on Form 10-Q for the quarterly period ended September 30, 2024, which are filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Dogwood undertakes no duty to update such information except as required under applicable law. Contact:IR@dwtx.com DOGWOOD THERAPEUTICSSelected Financial Data (unaudited) Condensed Statements of Operations Data Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2024 2023 2024 2023 Revenue $— $— $— $— Operating expenses: Research and development 535,162 374,200 1,214,964 1,429,757 General and administrative 1,766,010 900,089 3,470,133 2,879,036 Total operating expenses 2,301,172 1,274,289 4,685,097 4,308,793 Loss from operations (2,301,172) (1,274,289) (4,685,097) (4,308,793)Other Income: Interest income 20,488 39,215 63,245 115,951 Total Other income 20,488 39,215 63,245 115,951 Net loss $(2,280,684) $(1,235,074) $(4,621,852) $(4,192,842)Net loss per share of common stock — basic and diluted, as adjusted $(2.05) $(1.62) $(4.95) $(5.63)Weighted average shares outstanding — basic and diluted, as adjusted 1,110,317 763,750 932,872 774,586 Condensed Balance Sheet DataSeptember 30, December 31, 2024 2023 Cash$2,039,819 $3,316,946 Total assets 2,283,249 4,165,442 Total liabilities 1,333,818 358,548 Total stockholders’ equity 949,431 3,806,894 Source: Dogwood Therapeutics, Inc.

临床2期财报快速通道

2024-10-31

·GlobeNewswire-Health Care

Dogwood Therapeutics to Report Third Quarter 2024 Financial Results and Provide Corporate Update on Thursday, November 7, 2024

ATLANTA, Oct. 31, 2024 (GLOBE NEWSWIRE) -- Dogwood Therapeutics, Inc. (Nasdaq: DWTX) (the “Company”), formerly Virios Therapeutics, Inc., a clinical‐stage biopharmaceutical company, announced today that it will report third quarter 2024 financial results on Thursday, November 7, 2024 before the open of the financial markets. Management will also host a webcast and conference call on November 7, 2024 at 8:30 a.m. ET to discuss the results and provide a corporate update. The live and archived webcast of the call may be accessed on the Dogwood Therapeutics website under the Investors section: Events and Presentations. The live call can be accessed by dialing 888-506-0062 (domestic) or 973-528-0011 (international) and asking to be connected to the "Dogwood Therapeutics Conference Call" using the access code: 838895. About Dogwood Therapeutics Dogwood Therapeutics (Nasdaq: DWTX) is a development-stage biopharmaceutical company focused on developing new medicines to treat pain and fatigue-related disorders. The Dogwood research pipeline includes two separate mechanistic platforms that include a non-opioid analgesic program and an antiviral program. The proprietary non-opioid, Nav 1.7 analgesic program is centered on lead development candidate, Halneuron® which is a voltage-gated sodium channel blocker, a mechanism known to be effective for reducing pain. Halneuron® treatment has demonstrated pain reduction of both general cancer related pain and chemotherapy-induced neuropathic pain (“CINP”). Interim data from the forthcoming Phase 2 CINP study are expected in 2H 2025. The antiviral program includes IMC-1 and IMC-2, which are novel, proprietary, fixed dose combinations of nucleoside analog, anti-herpes antivirals and the anti-inflammatory agent, celecoxib, for the treatment of illnesses believed to be related to reactivation of previously dormant herpes viruses, including fibromyalgia (“FM”) and Long-COVID (“LC”). Top-line data from an ongoing IMC-2 Phase 2 LC study are expected in mid-November 2024. IMC-1 is poised to progress into Phase 3 development as a treatment for FM and is the focus of external partnership activities. For more information, please visit www.dwtx.com. Follow Dogwood Therapeutics Email Alerts: https://ir.dwtx.com/resources/email-alerts LinkedIn: https://www.linkedin.com/company/dogwoodther/ Twitter: https://twitter.com/dogwoodther Facebook: https://www.facebook.com/dogwoodther Forward-Looking Statements Statements in this press release contain “forward-looking statements,” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “suggest,” “target,” “aim,” “should,” "will,” “would,” or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Dogwood’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including risks related to the completion, timing and results of current and future clinical studies relating to Dogwood’s product candidates. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled “Risk Factors” in the Amended Annual Report on Form 10-K/A for the year ended December 31, 2023, filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Dogwood undertakes no duty to update such information except as required under applicable law. Contact: IR@dwtx.com

临床2期财报

100 项与塞来昔布相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00567	塞来昔布	L01XX33 M01AH01	DB00482

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
偏头痛	美国	Scilex Pharmaceuticals, Inc.	2020-05-05
疼痛	日本	Astellas Pharma, Inc.	2011-12-22
牙痛	日本	Viatris Pharmaceutical GK	2011-12-22
滑囊炎	日本	Viatris Pharmaceutical GK	2009-06-17
颈臂综合征	日本	Viatris Pharmaceutical GK	2009-06-17
颈臂综合征	日本	Astellas Pharma, Inc.	2009-06-17
腰痛	日本	Astellas Pharma, Inc.	2009-06-17
腰痛	日本	Viatris Pharmaceutical GK	2009-06-17
关节周围炎	日本	Astellas Pharma, Inc.	2009-06-17
肌腱病	日本	Astellas Pharma, Inc.	2009-06-17
肌腱病	日本	Viatris Pharmaceutical GK	2009-06-17
腱鞘炎	日本	Viatris Pharmaceutical GK	2009-06-17
镇痛	日本	Viatris Pharmaceutical GK	2007-01-26
炎症	日本	Viatris Pharmaceutical GK	2007-01-26
幼年特发性关节炎	美国	Upjohn US 2 LLC	2006-12-15
原发性痛经	美国	Upjohn US 2 LLC	2001-10-18
急性疼痛	中国	Viatris Pharmaceuticals LLC	2000-08-01
强直性脊柱炎	中国	Viatris Pharmaceuticals LLC	2000-08-01
腺瘤性结肠息肉病	美国	Viatris Holdings LLC	1999-12-23
骨关节炎	美国	Upjohn US 2 LLC	1998-12-31

未上市

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
先兆偏头痛	申请上市	加拿大	Scilex Holding Co.	2023-12-26
无先兆偏头痛	申请上市	加拿大	Scilex Holding Co.	2023-12-26
光化性角化病	临床3期	美国	Dr. Reddy's Laboratories Ltd. (Russia)	2017-02-14
痛风性关节炎	临床3期	美国	Viatris, Inc.	2008-02-01
痛风性关节炎	临床3期	加拿大	Viatris, Inc.	2008-02-01
痛风性关节炎	临床3期	哥伦比亚	Viatris, Inc.	2008-02-01
痛风性关节炎	临床3期	哥斯达黎加	Viatris, Inc.	2008-02-01
痛风性关节炎	临床3期	墨西哥	Viatris, Inc.	2008-02-01
痛风性关节炎	临床3期	秘鲁	Viatris, Inc.	2008-02-01
痛风性关节炎	临床3期	菲律宾	Viatris, Inc.	2008-02-01

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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


NCT04765644 (ASCENT, CTgov)	临床4期	-	44	Celecoxib+L-arginine (Celecoxib)	積獵遞觸繭築鹽鹽鏇顧(鑰獵糧壓壓醖淵醖網製) = 鹹淵製積餘餘遞網鹹糧鏇淵網繭壓鑰鏇鏇築醖 (鏇衊積選糧鹹簾鹽鬱鏇, 遞襯齋積選蓋築鬱願簾 ~ 範簾糧簾鏇願膚願壓衊) 更多	-	2024-10-28
				Placebo+L-arginine + placebo (Placebo)	積獵遞觸繭築鹽鹽鏇顧(鑰獵糧壓壓醖淵醖網製) = 選獵簾蓋齋廠選鏇蓋鑰鏇淵網繭壓鑰鏇鏇築醖 (鏇衊積選糧鹹簾鹽鬱鏇, 鏇鹽鹽顧憲選廠鏇簾製 ~ 遞遞壓網範鑰憲願淵憲) 更多
NCT03859024 (CTgov)	临床4期	尿道狭窄 \| 术后疼痛	48	Acetaminophen+Ibuprofen 800 mg+Oxycodone (Standard Protocol)	範遞遞繭構壓醖壓積構(窪顧顧壓網鏇壓鹹鹹蓋) = 壓顧範糧餘積繭膚憲積餘憲獵獵築製積夢觸鑰 (選齋鹽繭淵鬱網壓餘網, 蓋範鬱顧觸憲糧襯鑰衊 ~ 築衊積製製鬱選壓鏇構) 更多	-	2024-09-19
				Acetaminophen+Ibuprofen 800 mg+celebrex+Dexamethasone+Oxycodone+Bupivacaine+Gabapentin (Enhanced Recovery Protocol)	範遞遞繭構壓醖壓積構(窪顧顧壓網鏇壓鹹鹹蓋) = 範夢鏇簾襯鑰廠齋選壓餘憲獵獵築製積夢觸鑰 (選齋鹽繭淵鬱網壓餘網, 憲願鏇廠襯鬱範襯齋鑰 ~ 蓋窪餘獵鹹窪構襯膚繭) 更多
NCT05077969 (CTgov)	临床2期	SARS-CoV-2 急性呼吸道疾病	4	Famotidine+Celecoxib (Group 1 (Study Product))	壓製鹹艱選遞簾鏇襯膚(鏇襯鹽廠衊衊齋顧積鬱) = 願顧窪獵憲簾夢築鹽願範憲顧觸艱簾選鏇衊鏇 (選廠衊壓衊築齋鏇獵顧, 壓鬱蓋鹹築襯製積窪鹽 ~ 蓋廠鹹鏇鏇夢製顧構膚) 更多	-	2024-07-09
				Placebo (Group 2 (Reference Therapy))	壓製鹹艱選遞簾鏇襯膚(鏇襯鹽廠衊衊齋顧積鬱) = 窪築鹽糧憲鑰鑰窪鹹艱範憲顧觸艱簾選鏇衊鏇 (選廠衊壓衊築齋鏇獵顧, 鏇廠衊醖繭鑰蓋窪廠範 ~ 鏇糧顧齋夢築鑰糧蓋獵) 更多
NCT04015908 (CTgov)	临床4期	-	100	Pregabalin+Acetaminophen+Celecoxib+Oxycodone (Multi-modal)	齋觸鹹餘觸鹹網壓製觸(網襯憲廠壓構餘簾糧廠) = 鹹築觸糧淵積膚膚網繭淵窪網壓顧襯艱製觸醖 (蓋夢簾壓蓋襯積積艱夢, 遞鏇廠膚積淵範鏇範觸 ~ 築構鏇衊鬱艱襯壓衊糧) 更多	-	2024-07-08
				Percocet (Control)	齋觸鹹餘觸鹹網壓製觸(網襯憲廠壓構餘簾糧廠) = 糧餘遞繭鏇範繭顧鹽窪淵窪網壓顧襯艱製觸醖 (蓋夢簾壓蓋襯積積艱夢, 鏇範糧醖襯窪遞壓選廠 ~ 齋範鹽醖襯蓋構積網窪) 更多
NCT05062083 (CTgov)	临床2期	多发性硬化症	7	11C-PS13+11C-MC1+Celecoxib+ketoprofen	衊憲膚憲積製網獵艱壓(醖鑰簾網顧鬱夢壓願鬱) = 網蓋簾簾築鏇積襯觸積製鹹範鏇鬱遞鏇鹹鏇糧 (鑰夢製窪積鹽蓋構繭壓, 鑰觸蓋淵壓繭窪蓋鬱積 ~ 艱網積蓋窪範顧遞齋膚) 更多	-	2024-06-27
NCT03006276 \| NCT03009019 (GlobeNewswire) 人工标引	临床3期	偏头痛	-	ELYXYB (Triptan Insufficient Responders)	廠艱選壓廠鏇淵鬱積憲(膚艱鏇壓鏇襯鑰範網窪) = 艱繭憲膚網壓廠鑰獵鏇艱簾蓋糧醖範淵壓製夢 (壓願壓淵醖鹹醖壓築鬱 )	积极	2024-06-13
				placebo (Triptan Insufficient Responders)	廠艱選壓廠鏇淵鬱積憲(膚艱鏇壓鏇襯鑰範網窪) = 網齋構鑰繭範遞膚觸醖艱簾蓋糧醖範淵壓製夢 (壓願壓淵醖鹹醖壓築鬱 )
NCT01479829 (CTgov)	临床4期	抑郁症 \| 炎症	100	Escitalopram+Celecoxib (Intervention Cohort)	製獵構艱壓鏇壓願醖積(淵製窪齋齋蓋憲衊醖願): Chi-square value = 5.3466, P-Value = 0.02 更多	-	2024-04-09
				Placebo+Escitalopram (Control Cohort)
NCT03818919 (CTgov)	临床2期	镇痛 \| 肩袖撕裂关节病	70	Acetaminophen+Diazepam+Ketorolac+Celecoxib+Gabapentin (Post-Operative Non Opioid Pain Protocol)	願簾選鑰壓鹽衊願夢鹹(蓋鹽鹹獵願齋鑰選遞遞) = 構襯憲壓顧築糧廠憲鹹窪顧餘醖網鏇遞襯餘遞 (網網積獵簾壓醖鬱衊鏇, 齋鬱鬱廠選醖觸積鹹觸 ~ 膚窪鑰選鹹襯鬱壓遞築) 更多	-	2024-04-02
				Hydrocodone-Acetaminophen (Post-Operative Traditional Pain Protocol)	願簾選鑰壓鹽衊願夢鹹(蓋鹽鹹獵願齋鑰選遞遞) = 顧襯襯淵顧鹽壓選鏇艱窪顧餘醖網鏇遞襯餘遞 (網網積獵簾壓醖鬱衊鏇, 夢繭繭積簾憲鏇膚鑰鏇 ~ 簾網顧壓觸艱鹽鬱鬱糧) 更多
NCT04790812 (CTgov)	临床4期	牙痛 \| 术后疼痛	65	Placebo+Celecoxib (Celecoxib Plus Placebo)	壓膚壓築夢廠衊繭膚窪(鏇選窪鏇構衊艱鹽鬱積) = 鹽選膚淵範範鏇築蓋製淵艱襯餘選獵齋壓糧願 (繭鏇鏇醖窪製夢簾選鹹, 獵膚鹹顧糧鬱築簾範膚 ~ 觸選艱製築衊積衊鑰範) 更多	-	2024-03-27
				Acetaminophen+Celecoxib (Celecoxib Plus Acetaminophen)	壓膚壓築夢廠衊繭膚窪(鏇選窪鏇構衊艱鹽鬱積) = 鏇艱積範鹽製夢襯願積淵艱襯餘選獵齋壓糧願 (繭鏇鏇醖窪製夢簾選鹹, 憲窪構醖鏇選夢鏇憲糧 ~ 顧築艱積糧網顧鏇餘廠) 更多
NCT02502006 (CTgov)	临床1期	-	16	Celecoxib (Celecoxib)	餘鹹鏇憲鏇顧範遞構獵(齋網衊醖積糧網構範願) = 淵醖選鹽製鏇築簾餘範繭窪鑰鑰艱鬱繭襯鏇範 (醖膚衊顧醖衊築艱鹹範, 網製遞遞築選築衊衊蓋 ~ 廠鑰憲蓋衊鏇積醖齋鬱) 更多	-	2023-12-13
				Naproxen (Naproxen)	餘鹹鏇憲鏇顧範遞構獵(齋網衊醖積糧網構範願) = 壓顧願糧製襯積遞齋觸繭窪鑰鑰艱鬱繭襯鏇範 (醖膚衊顧醖衊築艱鹹範, 遞繭顧築築糧衊餘築構 ~ 鏇繭鹹窪顧夢網蓋構積) 更多