This is a prospective randomized placebo-controlled double-blind crossover pilot study determining the effect of dichloroacetate on brain function under clamped hypoglycemia in T1DM.

开始日期2025-05-06

申办/合作机构

Yale University

NCT05120284

/ Recruiting临床2期IIT

Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM)

Conduct a multicenter, open label Phase IIA trial of oral DCA in 40 surgical patients with recurrent GBM who have clinically indicated debulking surgery planned. No patients will be recruited at UF. Patients will be genotyped to establish safe dosing regimens and will be randomized to receive DCA (N=20) or no DCA (N=20) for one week prior to surgery. Deidentified blood and tumor tissue obtained at surgery will be assessed at UF for biochemical markers of DCA dynamics.

开始日期2022-07-01

申办/合作机构

University of Florida

NCT02616484

/ Active, not recruiting临床3期

Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

The objective of this research study is to conduct a pivotal phase 3 trial of treatment with the investigational drug dichloroacetate (DCA) in young children with deficiency of the pyruvate dehydrogenase complex (PDC). PDC deficiency (PDCD) is the most common cause of congenital lactic acidosis and is a frequently fatal metabolic disease of childhood for which no proven treatment exists. The investigators predict that DCA represents targeted potential therapy for PDCD because of its ability to increase both the catalytic activity and stability of the enzyme complex. The conclusions of numerous laboratory and clinical investigations are consistent with this postulate and have led to the designation of DCA as an Orphan Product for congenital lactic acidosis by the Food and Drug Administration.
A novel Observer reported outcome (ObsRO) survey that is completed by study participant's parent/caregiver, is the efficacy outcome measure.
Funding Source - FDA OOPD

开始日期2020-07-14

申办/合作机构

Saol Therapeutics, Inc.

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100 项与二氯乙酸相关的临床结果

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100 项与二氯乙酸相关的转化医学

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100 项与二氯乙酸相关的专利（医药）

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9,396

项与二氯乙酸相关的文献（医药）

2025-08-01·DESALINATION

Tracing disinfection byproducts during shock chlorination of a seawater reverse osmosis (RO) desalination pilot and the blended and chlorinated potable water produced

作者: Le, Thi Xuan Hoa ; Shang, Chii ; Xiang, Yingying ; Wang, Kun ; Lin, Chuanjing

Shock chlorination is an increasingly recognized strategy applied in seawater reverse osmosis (RO) desalination plants to mitigate membrane fouling.The obtained desalinated seawater is often blended with treated drinking water and subsequently chlorinated for domestic use.This study traced the formation of disinfection byproducts (DBPs) and the associated cytotoxicity during shock chlorination of a pilot seawater RO desalination system and the subsequent chlorination of the blended water at different blending ratios.Brominated DBPs (Br-DBPs) including tribromomethane, tribromoacetic acid, and dibromoacetic acid dominated right after shock chlorination.The dissolved air flotation combined with the sand filtration partially removed DBPs, possibly through volatilization, adsorption, biodegradation, and transformation of DBPs.The rejection rate of Br-DBPs was significantly higher than that of chlorinated DBPs, leading to the overall high RO rejection rate of trihalomethanes (THMs) (98.92 %), haloacetic acids (HAAs) (99.01 %), and haloacetonitriles (HANs) (94.47 %).In the chlorinated blended water, the total concentration of DBPs decreased while the fraction of Br-DBPs increased with increasing ratio of desalinated seawater, peaking at a blending ratio of 20 % of desalinated seawater.This is due to the dilution of DBPs and DBP precursors (i.e., natural organic matter) originated in treated drinking water by the desalinated seawater, which however increased Br- concentrations in the blended water.Brominated HANs and brominated HAAs were the main contributors to DBP-associated cytotoxicity.The blending ratio of 60 % or higher of desalinated seawater is suggested to minimize DBP concentration and cytotoxicity in the chlorinated blended water.The findings of this study enhance our understanding of the behavior of DBPs and their associated cytotoxicity during shock chlorination in seawater RO desalination plants and in chlorinated blended water, providing a theor. basis for real-world application.

2025-08-01·REPRODUCTIVE TOXICOLOGY

Exposure to disinfection by-products and risk of diminished ovarian reserve: Case-control evidence and cellular metabolomic insights

Article

作者: Fang, Ying ; Tian, Yichang ; Zhang, Jing ; Zhao, Xuehan ; Wang, Cong ; Wang, Zelin ; Wang, Qin ; Yang, Xiaokui ; Yang, Yi ; Wu, Jiaqi

Disinfection of drinking water is a critical measure for ensuring water safety and controlling waterborne infectious diseases. However, during the disinfection process, a variety of disinfection by-products (DBPs), some of which exhibit reproductive toxicity, are generated. This study aimed to assess whether DBP exposure contributes to the risk of diminished ovarian reserve (DOR) and explored the underlying metabolic mechanisms. A total of 182 participants, including 91 healthy women and 91 women with DOR, were recruited for a case-control study conducted between October 2023 and February 2024. Serum concentrations of DBPs, including dibromoacetic acid (DBAA), monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), chlorate, and perchlorate, were measured to evaluate DBP exposure. Key indicators for evaluating DOR included antral follicle count (AFC), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH). All six DBPs were higher in DOR patients (all p < 0.05). After controlling for covariates, all DBPs showed negative correlations with AMH and AFC, positive correlations with basal FSH, and a significant association with the risk of DOR (all p < 0.05). To further investigate the underlying mechanisms, we conducted an in vitro study using human ovarian granulosa cell line (KGN). KGN cells were exposed to DBAA and perchlorate for 48 hours, and metabolomic analysis was performed to identify altered metabolic pathways. Metabolomics data suggested that DBAA and perchlorate might have contributed to DOR by disrupting arginine biosynthesis and purine metabolism, respectively. In conclusion, DBPs exposure might have contributed to DOR risk by disrupting granulosa cell (GC) metabolism.

2025-07-01·PHYTOMEDICINE

Geniposide via enema alleviates colitis by modulating intestinal flora and bile acid metabolites, inhibiting S100A8/S100A9/NF-κB, and promoting TGR5 inhibition of NLRP3 inflammasome

Article

作者: Tian, Jing-Zhuo ; Liu, Mei-Ting ; Zhao, Yong ; Han, Jia-Yin ; Wang, Lian-Mei ; Liu, Su-Yan ; Yi, Yan ; Pan, Chen ; Tang, Xuan ; Wang, Xing-Wen ; Qin, Sha-Sha ; Zheng, Bao-Xin ; Liu, Chen-Yue ; Liang, Ai-Hua ; Li, Chun-Ying

BACKGROUND:

Geniposide (GE) has potential efficacy in treating ulcerative colitis (UC). However, its reactivity can be affected by rapid degradation after oral administration. Furthermore, increasing oral doses may lead to hepatotoxicity. Thus, We used enema administration, characterized by smaller dose and higher localized concentration in the lesion, to improve the above situation.

PURPOSE:

We aimed to confirm that enema administration is a better modality than oral administration for GE against UC and to explore its mechanism.

STUDY DESIGN/METHOD:

We established UC mouse model, monitoring Disease Activity Index (DAI), inflammatory cytokines levels, and histopathology. Macrogenomics and bile acid (BAs) metabolomics analysed the major intestinal flora and BAs. Simultaneouslly, we conducted quantitative proteomics analysis and screened core proteins and pathway. In vitro validation was taken by qPCR, immunofluorescence and immunoblotting experiments.

RESULTS:

GE via enema alleviate UC by inhibiting inflammatory factor production through downregulating S100A8/S100A9/NF-κB pathway. Analysis of the intestinal flora and BAs revealed that the enhanced abundance of Lachnospiraceae, which improves the ratio of primary to secondary BAs, and the reduced abundance of Provocaceae, which increases intestinal permeability and promotes inflammation, favored the restoration of the intestinal barrier. In addition, in vitro experiments confirmed that the key BA metabolites (mainly UDCA, DCA, and LCA) stimulated TGR5 signal to inhibit the assembly of the NLRP3 inflammasome and alleviated inflammation.

CONCLUSION:

We firstly confirmed that GE alleviates UC via the enema route in a better manner than the oral route, through enhancing the intestinal barrier, restoring intestinal flora and BAs homeostasis, and inhibiting inflammatory injury. This study initially revealed that GE can alleviate UC through elevating UDCA, DCA, and LCA levels at the colonic site to activate TGR5 receptor for inhibiting the NLRP3 inflammasome, in addition to downregulating the S100A8/S100A9/-TLR4-NF-κB pathway related inflammatory response directly. The evidences offer a promising strategy and profround meaning for UC treatment.

项与二氯乙酸相关的新闻（医药）

2025-02-05

·SYNAPSE

全球新药研发进展一周速递【02.05】

1. Vertex重磅急性镇痛新药获批上市 1月30日，Vertex Pharmaceuticals（福泰制药）宣布其首创选择性NaV1.8抑制剂Journavx（Suzetrigine/VX-548）获FDA批准上市，用于治疗中至重度急性疼痛，成为20多年来首个治疗中度至重度急性疼痛的新型药物，也是首个非阿片类口服疼痛信号抑制剂。VX-548是一种非阿片类、无成瘾性的选择性疼痛信号抑制剂。该药物靶向的NaV1.8是疼痛治疗的理想靶点，该靶点选择性表达于外周痛觉感受器和背根神经节内而非大脑中，因此不会导致成瘾。该药治疗中至重度急性疼痛的III期项目包括3项III期研究VX22-548-104、VX22-548-105和VX22-548-107，在2024年1月宣布积极结果。 2. 偏头痛新药获FDA批准上市 1月30日， Axsome Therapeutics宣布AXS-07（美洛昔康+利扎曲普坦）获FDA批准上市，用于治疗伴或不伴先兆的偏头痛急性发作。AXS-07是一种新型的、可口服的、快速吸收的、多机制复方药物，包含美洛昔康和利扎曲普坦两种活性成分。其中，美洛昔康是一种优先抑制环氧合酶-2（COX-2）的非甾体抗炎药，经Axsome的MoSEIC（分子溶解度增强包容复合物）技术平台设计后，其口服吸收速度显著加快，同时保持较长的血浆半衰期，可用于治疗偏头痛；而利扎曲普坦是一种5-羟色胺1B受体和1D受体（5-HT1B/5-HT1D）激动剂，与美洛昔康组成复方可以提供提供快速、疗效更强和持续的偏头痛缓解并减少症状复发。 3. 司美格鲁肽获FDA批准新适应症 1月28日，诺和诺德宣布Ozempic（1.0mg司美格鲁肽）获批用于降低2型糖尿病合并慢性肾病（CKD）成人患者因心血管疾病而恶化、肾衰竭（终末期肾病）和死亡的风险。司美格鲁肽是这类患者的第一个GLP-1治疗选择。FDA此次批准主要是基于IIIb期FLOW研究的主要结果。该研究是一项随机、双盲、安慰剂对照、优效性试验（n=3533），评估了Ozempic（1.0mg司美格鲁肽）与安慰剂作为肾脏结局标准治疗的辅助治疗方案来预防2型糖尿病合并CKD患者的肾损伤进展以及降低肾脏和心血管死亡风险的疗效和安全性。FLOW研究于2023年10月10日因疗效突出而提前终止。结果显示，与安慰剂组相比，Ozempic组患者的肾脏疾病进展以及心血管和肾脏死亡风险降低了24%，达到了优效性终点。 4. Enhertu新适应症获FDA批准，覆盖HER2超低表达乳腺癌 1月27日，第一三共与阿斯利康宣布Enhertu（德曲妥珠单抗）的补充生物制品许可申请（sBLA）获FDA批准，用于单药治疗在转移性环境中接受过至少一种内分泌治疗的不可切除或转移性HER2低表达（IHC 1+或IHC 2+/ISH-）或HER2超低表达（IHC 0）乳腺癌成人患者。FDA此次批准主要是基于III期DESTINY-Breast06研究的积极结果。该研究是一项全球性、多中心、随机、开放标签、对照临床试验（n=866），结果显示，在HR阳性、HER2低表达或HER2超低表达总人群中，Enhertu组患者的中位PFS相比标准治疗组显著延长（13.2 vs. 8.1个月，HR=0.63，P<0.0001），OS达到12个月的患者比例更高（87.0% vs. 81.1%，HR=0.81），确认的客观缓解率也更高（57.3% vs. 31.2%）。 5. 罕见病疗法在美国申报上市，纳入优先审评 1月31日，Saol Therapeutics宣布，美国FDA已受理其在研疗法SL1009的新药申请（NDA），用于治疗丙酮酸脱氢酶复合物缺乏症（PDCD）。FDA已授予该申请优先审评资格，并设定PDUFA日期为2025年5月27日。该NDA的提交主要基于3期双盲安慰剂对照交叉研究SL1009-01和生存研究SL1009-02的结果。此外，提交审评的证据还包括DCA的作用机制研究，以及非临床和临床数据，以全面评估其在PDCD患者中的安全性和临床获益。 6. 默沙东潜在重磅疗法3期试验结果积极，提前终止临床试验 1月31日，默沙东（MSD）宣布，进行中的HYPERION临床3期研究将提前终止。该研究评估其“first-in-class”疗法Winrevair（sotatercept）在新确诊为具有中高疾病进展风险的肺动脉高压（PAH）成年患者中的作用。这是该项目的外部指导委员会和默沙东基于ZENITH试验中期分析的积极结果所做出的决定。默沙东已与美国FDA就此决定进行讨论，HYPERION试验将提前终止，并已通知HYPERION研究的相关研究人员，让所有PAH患者有机会接受Winrevair治疗，默沙东则将对数据进行最终分析。Winrevair是一款“first-in-class”的IIA型激活素受体（ActRIIA）融合蛋白。 7. 一线肝癌！百时美施贵宝O+Y组合疗法有望在欧盟获批 2月1日，百时美施贵宝（Bristol Myers Squibb）宣布，欧洲药品管理局（EMA）人用药品委员会（CHMP）已推荐批准其重磅PD-1抑制剂Opdivo（nivolumab）与CTLA-4靶向抗体Yervoy（ipilimumab）联合疗法用于不可切除或晚期肝细胞癌（HCC）成人患者的一线治疗。这次CHMP的推荐主要基于3期CheckMate-9DW临床试验的积极研究结果。分析显示，在中位随访期约为35.2个月期间，Opdivo联合Yervoy治疗在临床与统计学上显著延长主要终点OS。接受Opdivo加Yervoy联合疗法患者的中位OS为23.7个月（95% CI：18.8–29.4），而接受活性对照药物治疗患者的中位OS为20.6个月（95% CI：17.5–22.5），风险比为0.79（0.65–0.96；p=0.018）。总生存期获益在各患者亚组中大致一致。 8. 安进双特异性抗体Blincyto新适应症获欧盟批准 1月30日，安进（Amgen）日前宣布，欧洲委员会（EC）已批准其双特异性抗体疗法Blincyto（blinatumomab）单药疗法作为巩固治疗的一部分，用于治疗新确诊的费城染色体阴性、CD19阳性的B细胞前体急性淋巴细胞白血病（B-ALL）成人患者。Blincyto是安进公司开发的CD3/CD19双特异性T细胞接合器（BiTE）。研究结果显示，与单独化疗相比，在多阶段巩固化疗方案中加入Blincyto可显著改善患者的总生存期（OS）。中位随访4.5年后，Blincyto联合化疗组（n=112）患者的5年总生存率为82.4%，而单独化疗组（n=112）为62.5%。 9. SMA领域首个肌肉靶向疗法！单抗疗法递交上市申请 1月29日，Scholar Rock今日宣布，已向美国FDA提交其单抗疗法apitegromab用于治疗脊髓性肌萎缩症（SMA）患者的生物制品许可申请（BLA）。公司同时计划于2025年第一季度向欧洲药品管理局（EMA）提交上市许可申请（MAA）。根据新闻稿，apitegromab是首个在SMA关键性3期试验中，患者表现出临床和统计学上显著运动功能改善的肌肉靶向治疗候选药物。该BLA主要基于3期SAPPHIRE试验和2期TOPAZ试验的数据支持。 10. 罗氏放弃多条TIGIT管线 1月30日，罗氏发布2024年财报，同时更新了研发管线。值得注意的是，罗氏此次放弃了多条TIGIT抗体tiragolumab的适应症开发管线，2项三期临床、2项二期临床、联合治疗的一期临床探索全部移出管线。与此同时，罗氏放弃了FAP/4-1BB双抗、HER2/CD3双抗、GPC3/CD3双抗、IL-15等多条研发管线。新加入的临床管线新分子，包括收购Poseida的实体瘤通用CAR-T疗法，信达生物引进的DLL3 ADC，KRAS G12D抑制剂等。 1. 亚盛医药完成美股IPO上市，募资1.26亿美元 1月28日，Ascentage Pharma（纳斯达克股票代码：AAPG）（香港交易所股票代码：6855）宣布在承销折扣和佣金之前，其7325000股美国存托股（“ADS”）的美国首次公开募股已完成，每股ADS的公开发行价格为17.25美元。每份ADS代表Ascentage Pharma的四股普通股。扣除承销折扣和佣金以及Ascentage Pharma应付的其他发行费用之前，此次发行的总收益约为1.264亿美元。此外，Ascentage Pharma已授予承销商30天的选择权，以初始公开发行价格购买最多1098750股ADS，减去承销折扣和佣金。ADS于2025年1月24日在纳斯达克全球市场开始交易。 2. 9700万美元B轮融资，开发CNS小核酸新药 1月28日，波士顿，Atalanta Therapeutics是一家开创性的RNA干扰（RNAi）治疗神经系统疾病的生物技术公司，宣布完成9700万美元的B轮融资，以支持该公司针对KCNT1相关癫痫和亨廷顿氏病的RNAi疗法的1期临床试验。此次融资由EQT Life Sciences和Sanofi Ventures共同领投，其他新投资者RiverVest Venture Partners、Novartis Venture Fund、由abrdn Inc管理的基金、Pictet Alternative Advisors、Mirae Asset Financial Group和GHR Foundation以及现有投资者F-Prime Capital共同参与。B轮融资使Atalanta迄今为止通过融资和合作产生的总资本达到2.62亿美元。 3. 旺山旺水生物申请港交所上市 1月27日，港交所官网显示，苏州旺山旺水生物医药股份有限公司（以下简称：旺山旺水生物）递交港交所上市申请，中信证券为保荐人。招股书显示，旺山旺水生物成立于2013年，是一家综合一体化生物医药公司，致力于发现、开发和商业化创新小分子药物。旺山旺水生物的使命是以创新改善患者的健康和生活质量，致力于满足重点治疗领域（即(i)病毒感染、(ii)神经精神及(iii)生殖健康）中患者不断变化的多样化需求。在过去的12年里，旺山旺水生物不仅构建起覆盖「研究－临床开发－制造－商业化」全产业价值链的端到端能力，还开发了由九款创新资产（包括三款核心产品VV116、LV232 及TPN171）组成的卓越创新管线，其中每款产品均具备同类首创或最佳潜力。 4. 派格生物过聆讯，即将赴港上市 1月28日，港交所官网显示，派格生物医药（苏州）股份有限公司（简称：派格生物）通过港交所聆讯，中金公司为独家保荐人。招股书显示，派格生物成立于2008年，是一家专注于自主研究及开发慢性病创新疗法（主要为肽和小分子药物）的生物技术公司，重点关注代谢紊乱领域。目前，派格生物已自主开发一款核心产品及其他五款候选产品，以把握2型糖尿病（T2DM）、肥胖症、非酒精性脂肪性肝炎（NASH）、阿片类药物引起的便秘（OIC）及先天性高胰岛素血症等常见慢病及代谢疾病的市场机会。 5. 减肥药新锐Metsera公司在纳斯达克上市，首日大涨47% 1月31日，聚焦新一代减肥药物的Metsera在纳斯达克挂牌上市，募资2.75亿美元，首日股价大涨47%，目前市值为27.8亿美元。Metsera成立于2022年，由Population Health Partners和ARCH Venture Partners创立‌，通过外部引进建立起减肥药组合管线。长效类管线MET-097i、MET-233i、MET-067i来自于对英国初创公司Zihipp的收购。口服的MET-002和MET-224o、GLP-1/GIP/GGG三靶点激动剂等从韩国生物技术公司D&D引进。首发管线MET-097i为超长效GLP-1，半衰期为15-16天，为司美格鲁肽的2倍，目标是实现每月一次给药，目前在2b期临床阶段，每月一次给药的临床数据将在2025年底至2026年初读出。 6. 基石药业与SteinCares就舒格利单抗在拉丁美洲地区达成战略合作 1月27日，基石药业宣布与深耕拉丁美洲市场的领先医药公司SteinCares达成商业化战略合作。根据许可及商业化协议，SteinCares将获得舒格利单抗在拉丁美洲地区，包括巴西、阿根廷、墨西哥、智利、哥伦比亚、哥斯达黎加、巴拿马、秘鲁、危地马拉、厄瓜多尔十个国家的商业化权利。在双方的合作中，SteinCares将负责舒格利单抗在上述地区的注册及商业化相关活动，而基石药业将负责舒格利单抗的产品供应，并将从SteinCares获得首付款、注册及销售里程碑付款，以及通过向SteinCares销售舒格利单抗来获取国际收入。 7. AdvanCell公司完成超1亿美元C轮融资，助力开发潜在同类最佳核药疗法 2月3日，AdvanCell公司宣布成功完成了超额认购的1.12亿美元C轮融资。本轮融资由SV Health Investors、赛诺菲创投、Abingworth以及SymBiosis共同领投，现有投资者Morningside与新投资者Tenmile、Brandon Capital及其他机构也提供了支持。这笔融资将助力AdvanCell持续扩大其生产能力，加速其放射性配体疗法管线的临床开发。目前，AdvanCell正在为1/2期临床试验TheraPb的最高剂量组招募转移性前列腺癌患者。ADVC001为一款潜在“best-in-class”的放射性配体疗法，可通过与前列腺特异性膜抗原（PSMA）结合的配体靶向递送释放α粒子的铅212同位素。内容来源于网络，如有侵权，请联系删除。

上市批准临床终止优先审批融资合作抗体

2025-01-31

·药明康德

创新小分子疗法获FDA优先审评资格

▎药明康德内容团队编辑日前，Saol Therapeutics宣布，美国FDA已受理其在研疗法SL1009的新药申请（NDA），用于治疗丙酮酸脱氢酶复合物缺乏症（PDCD）。FDA已授予该申请优先审评资格，并设定PDUFA日期为2025年5月27日。 PDCD是一种罕见且危及生命的线粒体疾病，该疾病影响人体碳水化合物的氧化过程，主要损害神经系统和骨骼肌，导致腺苷三磷酸（ATP）生成减少，引发能量衰竭。SL1009是一款二氯乙酸钠（DCA）口服溶液，其可抑制丙酮酸脱氢酶激酶（PDK），从而激活残余的丙酮酸脱氢酶复合物（PDC），促进线粒体ATP生成，提高能量供应。该NDA的提交主要基于3期双盲安慰剂对照交叉研究SL1009-01和生存研究SL1009-02的结果。此外，提交审评的证据还包括DCA的作用机制研究，以及非临床和临床数据，以全面评估其在PDCD患者中的安全性和临床获益。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Saol Therapeutics announces FDA acceptance of New Drug Application for SL1009 for treatment of Pyruvate Dehydrogenase Complex Deficiency. Retrieved January 31, 2025 from https://www.prnewswire.com/news-releases/saol-therapeutics-announces-fda-acceptance-of-new-drug-application-for-sl1009-for-treatment-of-pyruvate-dehydrogenase-complex-deficiency-302361297.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

优先审批临床3期临床结果

2025-01-28

·PRNewswire

Saol Therapeutics announces FDA acceptance of New Drug Application for SL1009 for treatment of Pyruvate Dehydrogenase Complex Deficiency

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, Jan. 28, 2025 /PRNewswire/ -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for SL1009, Sodium Dichloroacetate Oral Solution (DCA). DCA will be used with a proprietary genetic test to treat an orphan pediatric mitochondrial disease, Pyruvate Dehydrogenase Complex Deficiency (PDCD)1. The FDA granted Priority Review for the NDA and has set a goal date of May 27, 2025, under the Prescription Drug User Fee Act (PDUFA). Priority review is designated to applications for drugs that, if approved, would provide a significant improvement in safety or effectiveness of the treatment, prevention or diagnosis of a serious medical condition. SL1009 has previously been granted Orphan Drug and Fast Track Designations. SL1009 has also been granted a Rare Pediatric Disease Designation by the FDA and thus is eligible for a Priority Review Voucher (PRV). PDCD is a rare and life-threatening mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure. DCA is a targeted therapy that inhibits Pyruvate Dehydrogenase Kinase (PDK) to stimulate residual Pyruvate Dehydrogenase Complex (PDC) activity and increase energy (ATP) production by mitochondria. "This NDA acceptance brings us one step closer to addressing the critical health challenges faced by these children and their families, where no approved treatment is currently available," said Dave Penake, Chief Executive Officer of Saol Therapeutics. "Reaching this regulatory milestone is both a significant scientific achievement and a deeply meaningful moment for everyone who has dedicated themselves to advancing this therapy. Further, designating our application for priority review reaffirms that the FDA views PDCD as a serious condition" The NDA is supported by results from a Phase 3 double-blind placebo-controlled cross-over study (SL1009-01) and a survival study (SL1009-02). The totality of evidence submitted for review in the NDA includes mechanistic characterization, along with nonclinical and clinical evidence to demonstrate the safety and clinical benefit of DCA in PDCD patients. DCA is not currently approved for any indication in the United States. About Pyruvate Dehydrogenase Complex Deficiency (PDCD) PDCD is a mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure. It is estimated that 300-500 patients are treated in expert centers in the US, and the overall prevalence is thought to be as high as 2,000. PDCD is the most common cause of congenital lactic acidosis, a life-threatening condition that may occur as early as the neonatal period. Patients suffering from PDCD may also exhibit extreme tiredness (lethargy), poor feeding, rapid breathing (tachypnea), and other signs of neurological and neuromuscular dysfunction such as developmental delay, low muscle tone (hypotonia), abnormal eye movements and seizures. Signs and symptoms usually begin soon after birth but may appear later in childhood2. There are currently no FDA-approved therapies for PDCD. About Saol Therapeutics Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit . Saol Therapeutics Contact Brian Nappi, Senior Vice President, Strategy [email protected] References 1. , Accessed January 2025 2. Ganetzky R, McCormick EM, Falk MJ. Primary Pyruvate Dehydrogenase Complex Deficiency Overview. 2021 Jun 17. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. PMID: 34138529. SOURCE Saol Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期优先审批快速通道申请上市孤儿药

100 项与二氯乙酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05857	二氯乙酸	-	DB08809

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适应症	最高研发状态	国家/地区	公司	日期
丙酮酸脱氢酶复合物缺乏症	申请上市	美国	Saol Therapeutics, Inc.	2024-12-03
先天性乳酸酸中毒	临床3期	-	University of Florida	1998-10-01
乳酸性酸中毒	临床3期	-	Mallinckrodt Plc	-
乳酸性酸中毒	临床3期	-	The Valens Co., Inc.	-
创伤性脑损伤	临床3期	-	The Valens Co., Inc.	-
创伤性脑损伤	临床3期	-	Mallinckrodt Plc	-
心肌缺血	临床3期	-	Mallinckrodt Plc	-
心肌缺血	临床3期	-	The Valens Co., Inc.	-
多形性胶质母细胞瘤	临床2期	美国	Saol Therapeutics, Inc.	2022-07-01
多形性胶质母细胞瘤	临床2期	美国	University of Florida	2022-07-01

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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


NCT01386632 (Pubmed) 人工标引	临床2期	局部晚期头颈部鳞状细胞癌	45	Chemoradiotherapy+dichloroacetate	遞網簾積鏇製製網窪鹹(觸鹽醖獵鹽窪壓鏇醖鏇) = However, there were no significant differences in grade 3/4 AE rates. 願積鏇糧膚選範餘選鑰 (製糧選網醖鑰廠鬱選艱 ) 更多	积极	2022-03-21
				Placebo
NCT01386632 (CTgov)	临床2期	晚期头颈癌 \| 头颈部鳞状细胞癌	50	DCA (dichloroacetate) (DCA (Dichloroacetate) Treatment)	襯繭衊網積觸艱壓醖醖 = 淵鏇壓觸獵淵壓簾糧夢製餘築艱顧窪廠憲願鬱 (窪觸鏇選築觸築窪願選, 鏇範鏇鬱鹽簾餘製鏇顧 ~ 夢製積鏇積積網淵鏇鏇) 更多	-	2017-06-14
				Placebo (Placebo)	襯繭衊網積觸艱壓醖醖 = 襯製網膚膚憲糧憲淵糧製餘築艱顧窪廠憲願鬱 (窪觸鏇選築觸築窪願選, 醖願衊製構蓋鏇築窪鑰 ~ 積襯選範網顧鹹製簾壓) 更多
NCT01029925 (CTgov)	临床2期	转移性乳腺癌	7	Dichloroacetate (DCA)	觸艱鹹憲淵衊醖憲襯糧 = 窪網製範構觸製構簾鏇顧鏇製鹽壓構淵壓窪廠 (廠鬱網鑰窪築積選觸簾, 壓齋壓遞鹽夢蓋鏇艱簾 ~ 壓網餘選衊範襯窪繭觸) 更多	-	2016-02-12
NCT01386632 (ASCO2015)	临床2期	局部晚期头颈部鳞状细胞癌	50	Dichloroacetate (DCA)	築選鏇窪觸醖衊壓範餘(蓋選顧積醖糧醖鏇膚鑰) = not significantly different (16% DCA vs 4% P; p = 0.35) 願範窪範醖構獵衊憲積 (壓範網憲觸淵簾鏇艱製 ) 更多	-	2015-05-20
				Placebo
NCT01029925 (Pubmed \| J Cancer Res Clin Oncol)	临床2期	缺氧 \| 晚期非小细胞肺癌	7	Dichloroacetate	鹹鏇鹽廠憲齋膚鹹憲觸(醖膚選獵衊壓壓願鏇壓) = two patients had disease progression prior to the first scheduled scans 齋遞糧糧範簾夢製簾觸 (鹽淵淵簾簾網築糧構艱 ) 更多	-	2014-03-01
AACR2012	N/A	乳腺癌	-	Dichloroacetate (DCA)	淵艱窪壓齋願鹹齋遞築(鬱遞獵衊廠憲獵糧顧範) = 製鹹蓋鬱簾淵鹽憲淵餘範醖顧窪襯繭觸製鏇廠 (顧製鏇夢壓憲製夢膚築 )	-	2012-04-15