Pneumonitis Prevention Protocol Using Pentoxifylline and Α-tocopherol in Stage III Non-Small Cell Lung Cancer Patients Undergoing Chemoradiation (P4-PACIFIC)

Currently, the standard of care treatment for newly diagnosed, inoperable stage III non-small cell lung cancer is radiotherapy (RT) with concurrent chemotherapy, followed by immune checkpoint inhibitors (ICI). RT is a highly effect local treatment. However, high doses of radiation used in curative settings can cause adverse side effects. The most common RT side effect in lung cancer is Radiation Induced Lung Injury (RILI), which can manifest as pneumonitis and/or pulmonary fibrosis. Lung injury can negatively impact patients' well-being and quality of life, and may lead to increased mortality. Risk of lung injury is particularly increased when patients are treated with a combination of treatments (i.e., RT, chemotherapy, and ICI). The drug Pentoxifylline (in combination with α-Tocopherol (Vitamin E)) has been shown to prevent/alter the progression of lung injury and there is a growing body of evidence to support the safety and efficacy of phosphodiesterase inhibitors in cancer treatment. The proposed study aims to determine if the addition of Pentoxifylline, given in combination with α-Tocopherol (Vitamin E), to standard of care treatment will reduce side effects related to lung injury and improve quality of life in this study population.

开始日期2024-11-30

申办/合作机构

University Health Network

[+1]

IRCT20240316061302N1 / Suspended临床2/3期IIT

Investigation of vitamin C and vitamin E co-treatment in improvement of clinical and paraclinical findings of lung contusion patients

开始日期2024-10-22

申办/合作机构

Kerman Medical University

RBR-99h2qmf / Not yet recruitingN/AIIT

Vitamin E Supplementation in pregnant women with Severe Preeclampsia

开始日期2024-10-01

申办/合作机构

Universidade Federal do Rio Grande do Norte

100 项与维生素E 相关的临床结果

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100 项与维生素E 相关的转化医学

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100 项与维生素E 相关的专利（医药）

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46,132

项与维生素E 相关的文献（医药）

2025-02-01·Current drug delivery

From Vision Correction to Drug Delivery: Unraveling the Potential of Therapeutic Contact Lens

Article

作者: Sharma, Mohit ; Saini, Ankush ; Swami, Rajan ; Singh, Indu

Contact lenses (CLs) have become an essential tool in ocular drug delivery, providing effective treatment options for specific eye conditions. In recent advancements, Therapeutic CLs (TCLs) have emerged as a promising approach for maintaining therapeutic drug concentrations on the eye surface. TCLs offer unique attributes, including prolonged wear and a remarkable ability to enhance the bioavailability of loaded medications by more than 50%, thus gaining widespread usage. They have proven beneficial in pain management, medication administration, corneal healing, and protection. To achieve sustained drug delivery from TCLs, researchers are exploring diverse systems, such as polymeric nanoparticulate systems, lipidic systems, and the incorporation of agents like vitamin E or rate-limiting polymers. However, despite breakthrough successes, certain challenges persist, including ensuring drug stability during processing and manufacturing, controlling release kinetics, and biomaterial interaction, reducing protein adhesion, and addressing drug release during packaging and storage etc. While TCLs have shown overall success in treating corneal and ocular surface disorders, careful consideration of potential issues and contraindications is vital. This review offers an insightful perspective on the critical aspects that need to be addressed regarding TCLs, with a specific emphasis on their advantages and limitations.

2025-01-01·SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

Impact of ambient conditions on the minor nutrients content in spirulina “Arthrospira platensis” (AP) extracted from Lake Chad revealed by fluorescence spectroscopy coupled with chemometric methods

作者: Palé, Wang-Yang ; Kogniwali, Sagesse Bel Christ Gredibert ; Owono, Luc Calvin Owono ; Kenfack, Cyril Assongo ; Kogniwali-Gredibert, Sagesse Bel Christ ; Lissouck, Daniel ; Zoutchibé, Joseph ; Yacoub, Idriss Halawlaw ; Wembé, Evariste Tafo ; Tafo, Evariste Wembé

2025-01-01·BEHAVIOURAL BRAIN RESEARCH

Coenzyme Q10 and vitamin E alleviate heat stress-induced mood disturbances in male mice: Modulation of inflammatory pathways and the HPA axis

Article

作者: Mahmoudi, Javad ; Morsali, Soroush ; Athari, Seyed Zanyar ; Farajdokht, Fereshteh ; Sadigh-Eteghad, Saeed ; Hosseini, Leila ; Ahmadi, Mahdi ; Vatandoust, Seyedmahdi ; Bahari, Leila ; Kazmi, Sareh

Heat stress, as an environmental stressor, can lead to temperature dysregulation and neuroinflammation, causing depression and anxiety by disrupting brain physiology and functional connectivity. This study looked at how co-enzyme Q10 (Q10) and vitamin E (Vit E), alone and together, affected heat stress-caused anxiety and depression symptoms and inflammation in male mice. Five groups were utilized in the study: control, heat stress (NS), Q10, Vit E, and the combination group (Q10+Vit E). The mice were subjected for 15 min/day to a temperature of 43°C for 14 consecutive days, followed by daily treatments for two weeks with either normal saline, Q10 (500 mg/kg), Vit E (250 mg/kg), or their combination. The forced swimming test (FST) and tail suspension test (TST) were employed to evaluate despair behavior, whereas the elevated plus maze (EPM) and open field test (OFT) were used to assess anxious behaviors. Subsequently, the animals were sacrificed, and serum corticosterone levels, protein expression of inflammasome-related proteins, and hsp70 gene expression were evaluated in the prefrontal cortex (PFC). The study revealed that treatment with Vit E and Q10, alone or together, provided anxiolytic and antidepressant effects in the heat-stress-subjected animals. Also, giving Vit E and Q10 alone or together greatly lowered serum corticosterone levels. In the PFC, they also lowered the levels of hsp70 mRNA and NF-κB, caspase 1, NLRP3, and IL-1β proteins. It is speculated that treatment with Q10 and Vit E can attenuate heat stress-associated anxious and depressive responses by inhibiting the inflammatory pathways and modulating the hypothalamus-pituitary-adrenal axis.

324

项与维生素E 相关的新闻（医药）

2024-10-31

·PRNewswire

Lipocine Announces Distribution and License Agreement with SPC Korea to Commercialize TLANDO® in South Korea

SALT LAKE CITY, Oct. 31, 2024 /PRNewswire/ -- Lipocine Inc. (NASDAQ: LPCN), a biopharmaceutical company leveraging its proprietary technology platform to augment therapeutics through effective oral delivery, today announced a license, development and supply agreement with to SPC Korea granting exclusive rights to market TLANDO® in South Korea. Under the terms of the distribution and license agreement, Lipocine will receive an upfront payment and is also eligible to receive certain regulatory and sales milestone payments, including a payment upon regulatory approval of TLANDO in South Korea. Lipocine is entitled to royalties on net commercial sales. Lipocine will supply TLANDO to SPC Korea and will receive a supply price. SPC Korea will assume responsibility for obtaining regulatory approval within the territory. "We are very pleased to partner TLANDO with SPC Korea," said Dr. Mahesh Patel, President and Chief Executive Officer of Lipocine. "This license agreement represents a strategic opportunity to expand the global reach of TLANDO and to address the significant unmet medical need in South Korea. It underscores Lipocine's commitment to strategic partnerships that have the potential to drive growth and create value for our shareholders while advancing our goals to deliver innovative therapies to patients." About TLANDO TLANDO is approved by the US FDA as a testosterone replacement therapy ("TRT") in adult males indicated for conditions associated with a deficiency or absence of endogenous testosterone: primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired). It was developed using Lipocine's proprietary Lip'ral drug delivery technology platform. For full prescribing information, please visit . About Lipocine Lipocine is a biopharmaceutical company leveraging its proprietary technology platform to augment therapeutics through effective oral delivery to develop differentiated products. Lipocine has drug candidates in development as well as drug candidates for which we are exploring partnerships. Our drug candidates represent enablement of differentiated, patient friendly oral delivery options for favorable benefit to risk profile which target large addressable markets with significant unmet medical needs. Lipocine's clinical development candidates include: LPCN 1154, oral brexanolone, for the potential treatment of postpartum depression, LPCN 2101 for the potential treatment of epilepsy, LPCN 2203 an oral candidate targeted for the management of essential tremor, LPCN 2401 an oral proprietary combination of anabolic androgen receptor agonist and α-tocopherol, an antioxidant, as an adjunct therapy to incretin mimetics, as an aid for improved body composition in chronic weight management and LPCN 1148, a novel androgen receptor agonist prodrug for oral administration targeted for the management of symptoms associated with liver cirrhosis. Lipocine is exploring partnering opportunities for LPCN 1107, our candidate for prevention of preterm birth, LPCN 1154, for rapid relief of postpartum depression, LPCN 2401 for chronic weight management, LPCN 1148, for the management of decompensated cirrhosis, and LPCN 1144, our candidate for treatment of non-cirrhotic NASH. TLANDO, a novel oral prodrug of testosterone containing testosterone undecanoate developed by Lipocine, is approved by the FDA for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism, in adult males. For more information, please visit . Forward-Looking Statements This release contains "forward-looking statements" that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and include statements that are not historical facts regarding our product development efforts, our strategic plans for developing products, our ability to monetize product candidates, including through entering into partnering arrangements, our product candidates and related clinical trials, the achievement of milestones within and completion of clinical trials, the timing and completion of regulatory reviews, outcomes of clinical trials of our product candidates, and the potential uses and benefits of our product candidates. Investors are cautioned that all such forward-looking statements involve risks and uncertainties, including, without limitation, the risks that we may not be successful in developing product candidates, we may not have sufficient capital to complete the development processes for our product candidates, we may not be able to enter into partnerships or other strategic relationships to monetize our non-core assets, the FDA will not approve any of our products, risks related to our products, expected product benefits not being realized, clinical and regulatory expectations and plans not being realized, new regulatory developments and requirements, risks related to the FDA approval process including the receipt of regulatory approvals, and our ability to utilize a streamlined approval pathway for LPCN 1154, the results and timing of clinical trials, patient acceptance of Lipocine's products, the manufacturing and commercialization of Lipocine's products, and other risks detailed in Lipocine's filings with the SEC, including, without limitation, its Form 10-K and other reports on Forms 8-K and 10-Q, all of which can be obtained on the SEC website at . Lipocine assumes no obligation to update or revise publicly any forward-looking statements contained in this release, except as required by law. SOURCE Lipocine Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

引进/卖出上市批准

2024-10-28

·PRNewswire

Cocrystal Health Industry Announces Launch of Best in Class Bioabsorption and Stability Cocrystallized Lutein and Curcumin Technologies

Patented and clinically verified nutraceutical actives outperform current branded offerings and offer a powerful solution for supplement product potency concerns. LAS VEGAS, Oct. 28, 2024 /PRNewswire/ -- At the Supplyside West tradeshow this week representatives from Cocrystal Health Industry are announcing the launch of the Cocrystal Lutein and Curcumin powder actives. Backed by 60 global patents and near 100 published papers, the company leverages their proprietary and clean cocrystallization platform to produce actives with dramatically improved bioabsorption, stability and functionality relative to existing offerings. These launches build on their existing cocrystallized ingredient portfolio which includes Ubiquinol CoQ10, Hydroxytyrosol and Alpha Tocopherol Vitamin E. Continue Reading Cocrystal Curcumin Powder Cocrystal Lutein Powder Lutein is well demonstrated in clinical research to support eye health, though traditional lutein ingredients have poor bioabsorption, solubility, and stability, as the ingredient is easily oxidized. Powered by Cocrystal Health Industry's clean, vegan and non-GMO cocrystallization process, Cocrystal Lutein now provides a powerful solution to address these concerns. In 3rd party testing, Cocrystal Lutein demonstrated over 6 times greater bioabsorption and 3 times better solubility compared to current marketed lutein. In a head-to-head capsule stability study, the cocrystal advantage is even more dramatic. Cocrystal Lutein maintained over 99% of potency in capsules after 30 days, while current marketed lutein maintained less than 2% of its original potency. In addition to performance advantages, the cocrystal technology offers a significant cost savings relative to well known branded lutein. While well researched to support a range of benefits including joint and cognitive health, marketed curcumin extracts are similarly limited by very poor bioavailability. Patented Cocrystal Curcumin featuring L-Carnitine as a ligand has been shown in studies to offer over 10X greater bioabsorption in comparison to current marketed curcumin. And while there are several enhanced bioavailability curcumin materials available, in a head-to-head study Cocrystal Curcumin showed significantly better bioabsorption even relative to an existing enhanced offer. Alex Mei, PhD, Cocrystal Health Industry's Founder & CEO commented, "We are thrilled to expand our portfolio and introduce powerful new solutions in our Cocrystal Lutein & Curcumin technologies. Our proprietary platform solves for multiple nutrition brand concerns – providing meaningful differentiation and unparalleled benefit performance to their consumers, while ensuring sustained potency against label claim. As the global leader in cocrystallized active ingredients, we're proud to offer these transformative solutions." To learn more manufacturers and formulators can reach out to [email protected]. About Cocrystal Health Industry: Backed by 60 global patents and near 100 published papers, Cocrystal Health Industry introduces cocrystal powder technologies as unprecedented solutions for poor stability and low bioavailability ingredients. With demonstrated best in class bioavailability and superior in-formula stability, our actives also feature pure nature integrity, improved solubility, dissolution, melting point and flowability versus existing offerings. Beyond their superior performance, Cocrystal actives typically offer a cost advantage relative to other branded ingredients. The company's growing portfolio includes Cocrystal Ubiquinol, Hydroxytyrosol, Alpha Tocopherol, Rutin and now Lutein and Curcumin. For more information visit . Media Contact: Jeff Avila 305-632-1733 [email protected] SOURCE Cocrystal Health Industry WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2024-10-28

·药智网

2024年集体爆发的MASH市场，竞争格局几何？

继今年3月，全球首款MASH新药——Resmetirom获FDA批准用于治疗伴有肝纤维化的成人MASH患者，填补了MASH药物的空白状态后，近段时间以来，国内MASH领域的“新药曝光度”有目共睹的在增加。 10月15日，微芯生物宣布，其研发的西格列他钠治疗非酒精性脂肪性肝炎（NASH）/代谢相关性脂肪性肝炎（MASH）的2期临床研究（CGZ203试验）摘要入选美国肝病研究学会年会（AASLD 2024），11月17日以口头报告形式公布。 10月18日，中国国家药监局药品审评中心（CDE）官网公示，康弘药业1类THR-β新药KH629片获得临床试验默示许可，拟开发用于治疗成人非酒精性脂肪性肝炎。为何沉寂40余年的MASH新药研究，短时间内俨然成为“流量”的代名词，成为众多药企争相入局的潜力市场，其背后又是怎样的底层逻辑使然？患病率高涨 MASH是临床需求愈发迫切其实，与大多数肝脏慢性病不同，近年来非酒精性脂肪性肝病（NAFLD）的患病率不降反增，现阶段已取代乙肝成为我国最常见的慢性肝病。资料显示，中国成年人中NAFLD患病率高达29.2%，10年内整体增长10%，中国MASH患病率约为2.4%～6.1%，我国NAFLD/MASH患者疾病负担极其沉重。据弗若斯特沙利文报告预计， 2030 年全球 MASH 患病人数将达到 4.9 亿人，全球MASH药物市场将达到 322 亿美元。作为NAFLD中最严重的发展阶段，原理上MASH是一种与代谢紊乱相关的肝脏疾病，其特征是肝脏中脂肪的异常积累，伴随着炎症和肝细胞损伤，早年间被称为非酒精性脂肪性肝炎（NASH）。 40余年的相关研究下，人们对MASH的发病机制仍尚未完全明确，目前认为其乃是一种代谢应激性肝损伤，与多种因素相关，复杂的级联反应下的肝细胞损伤机制有以下几种，主要包括胰岛素抵抗、氧化应激、炎症反应和脂质代谢异常等多个环节。在临床表现方面，MASH通常情况下起病隐匿且缓慢，且通常无症状，多于常规检查过程中无意发现，并且由于MASH通常情况下难以自发缓解，在早期无干预的情况下进展为肝纤维化的风险很高，大约有15%的患者会发展为肝硬化、肝衰竭和肝细胞癌。临床药物缺乏 MASH传统治疗局限性大在Resmetirom获FDA批准上市之前，全球尚无治疗 NAFLD/NASH 的靶向性药物，而由于MASH与肥胖、2 型糖尿病、高血压、血脂紊乱等疾病的密切相关性，目前普遍认为控制这些疾病可有效改善 NAFLD/NASH的代谢状态，从而延缓疾病进展。因此，NAFLD以及MASH的治疗基础仍是生活方式的干预和饮食方案的优化，生活习惯的改善，尤其饮食的控制及锻炼减重等可减少肝脏脂肪沉积，有利于改善 MASH 的生化指标和肝组织学病变，相关研究显示，体重减轻 3% 即可改善 NAFLD患者脂肪肝病情程度，减重 7% 可改善肝脏炎症等组织学指标，减重 10% 可逆转肝纤维化水平。而在药物治疗方面，临床上主要针对抗胰岛素抵抗、抗氧化应激、降血脂、促进脂质代谢及保护肝细胞膜等对MASH进行治疗，如二甲双胍、维生素 E、熊去氧胆酸、FXR激动剂奥贝胆酸、肝损伤治疗药物等保肝药物的使用。但同时，上述药物治疗方式的局限性也很大，一者药物的治疗剂量、有效性及安全性均尚不明确，有待进一步研究；二者，如奥贝胆酸等FXR激动剂的不良反应也极大限制了其在MASH领域的应用。故现阶段的MASH临床治疗上，迫切需要一种副作用低、能逆转肝纤维化、患者顺应性佳的创新疗法。四大方向推动MASH机制逐渐清晰就目前而言，通过对MASH的发病机制研究，目前已有多款靶点给予了MASH有效干预，是目前乃至未来MASH治疗的主要方向。从类型上来看主要分为代谢、消化、抗炎、抗纤维化四种方向：代谢类：改善胰岛素敏感性、抑制脂肪生成各种酶、促进线粒体摄取脂肪酸等。消化类：调控肝肠轴的循环、改善胆汁酸的循环与信号传导、改善肠道菌群的平衡等。抗炎类：抑制炎症细胞聚集、阻断炎性信号传导、降低氧化作用和内质网应激反应、防止肝细胞凋亡等。抗纤维化：针对肝脏中的星形细胞、减轻肝脏中胶原蛋白的沉积、增强纤维分解等。而在这四种类型药物之下，又可以细分出不同的靶点选择，各靶点方向之下又存在不同的技术优势与产品差异。数据来源：公开数据整理（点击查看大图）据不完全统计，全球现有MASH在研疗法已突破350款。其中代谢类与消化类的数量最多，而前者主要机制集中于肝内，在逆转纤维化方面具有优势，而后者则是从肝外机制着手，在降低肝脏脂肪积累与纤维化进展方面优势明显，两者机制各有优劣，未来大概率会是协同合作的关系。临床阶段方面，虽绝大多数创新疗法均集中在临床前阶段，但跨入临床阶段的产品依旧不少，其中以临床II期管线数量最多，共计108款；而进入临床III期产品则也有18款之多。表1.MASH临床III期管线药品名称靶点适应症最高阶段原研单位利莫纳班 rimonabant CB1 临床Ⅲ期赛诺菲依碳酸瑞格列净 remogliflozin etabonate SLC5A2 临床Ⅲ期 BHV Pharma Inc;格兰马克制药有限公司沙格列扎镁 aroglitazar magnesium INS 临床Ⅲ期 Zydus Lifesciences Ltd 司美格鲁肽 semaglutide GLP-1R 临床Ⅲ期丹麦诺和诺德公司腺苷蛋氨酸 ademetionine Transferase 临床Ⅲ期雅培制药芦比前列酮 lubiprostone CFTR;ClC-2;PGE1 临床Ⅲ期 Sucampo Pharma LLC 佩玛贝特 pemafibrate PPAR-alpha 临床Ⅲ期 Kowa Co Ltd 塞拉德帕 seladelpar PPAR-delta 临床Ⅲ期 CymaBay Therapeutics Inc;强生创新制药 aramchol SCD1 临床Ⅲ期 Galmed Pharmaceuticals Ltd survodutide GLP-1R;GCGR 临床Ⅲ期 Zealand Pharma A/S;勃林格殷格翰 FXR314 NR1H4 临床Ⅲ期 Organovo Holdings inc 拉尼兰诺 lanifibranor PPAR-alpha;PPAR-delta;PPAR-gamma 临床Ⅲ期 Inventiva 可妥度肽 cotadutide GLP-1;GCGR 临床Ⅲ期阿斯利康瑟隆舍替selonsertib MAP3K5 临床Ⅲ期美国吉利德科学公司塞尼韦洛 cenicriviroc CCR2;CCR5 临床Ⅲ期 Tobira Therapeutics Inc;武田药品工业株式会社 ENB-106 / 临床Ⅲ期上海轶诺药业有限公司依鲁西夫明 efruxifermin FGF21 临床Ⅲ期安进公司 norucholic acid / 临床Ⅲ期德国霍克大药厂数据来源：药智数据三大靶点引领MASH新药加速落地就MASH在研药物靶点分布上而言，glp-1、FXR、THR-β、FGF19/21与PPAR是现阶段MASH最主要的在研药物类型。数据来源：药智数据从数量上来看，FXR激动剂、GLP1在研发热度上远超其他靶点，其在研数量也最多，目前均有超过30款相关疗法布局；其次是THR-β、FGF19/21与PPAR，分别有19、18与13款新药布局；其余靶点数量则相对较少，其临床阶段也相对靠后。从趋势上来看，FXR激动剂虽然是MASH领域的老牌靶点之一，但由于靶点特殊作用机制，其在副作用上的局限性太大，直接影响了其在临床上的应用潜力。至少就现在而言，反而是glp-1与THR-β两种机制的MASH新药更受关注，未来也更容易占据头牌。数据来源：药智数据 GLP-1 由于原理上GLP-1类似物能够有效改善糖脂代谢异常，因此GLP-1受体激动剂在糖尿病与减重适应症外，也被视为潜在的MASH治疗药物。表2.GLP-1应用于MASH的创新疗法药品名称靶点原研单位适应症最高阶段司美格鲁肽 semaglutide GLP-1R 丹麦诺和诺德公司临床Ⅲ期 survodutide GLP-1R;GCGR Zealand Pharma A/S;勃林格殷格翰临床Ⅲ期可妥度肽 cotadutide GLP-1;GCGR 阿斯利康临床Ⅲ期替尔泊肽 tirzepatide GIPR;GLP-1R 礼来制药临床Ⅱ期 RAY-1225 GLP-1;GIP 广东众生睿创生物科技有限公司临床Ⅱ期 HEC-88473 FGF21;GLP-1R 东莞市东阳光生物药研发有限公司临床Ⅱ期派维度肽 pemvidutide GLP-1R;GCGR Altor BioScience Corp合作：Altimmune Inc 临床Ⅱ期尤曲格鲁肽 utreglutide GLP-1R 印度太阳药业有限公司临床Ⅱ期巴度肽 bamadutide GLP-1R;GCGR 赛诺菲临床Ⅱ期依福培肽 efocipegtrutide GIPR;GLP-1R;GCGR 韩美药品株式会社临床Ⅱ期数据来源：药智数据截止目前，随着人们对 GLP-1 的焦点由减肥向在抗 MASH转变之下，已有超30种GLP-1药物正在研究其治疗MASH的潜力，临床上推进较快的产品不少，较出名的产品有诺和诺德的司美格鲁肽、勃林格殷格翰的survodutide、阿斯利康的cotadutide、礼来制药的tirzepatide。其中，Semaglutide与替尔泊肽作为GLP-1两大重磅产品，在关于MASH的治疗研究中均显示出减少肝脏脂肪积累、降低炎症水平的潜力，极大地振奋了行业对GLP-1作用于MASH的信心。但与此同时，GLP-1在治疗MASH上的局限性也逐渐体现，即虽然在减少肝脏脂肪积累和纤维化方面的效果显著，但对逆转肝脏纤维化上却缺乏足够、全面、多维度的有效证据。这就导致GLP-1疗法单药治疗既无法完全满足现有的临床需求，也很难与其他疗法拉开差距。对此，有关人士表示，GLP-1未来要想在MASH领域站稳脚跟，要么就逆转纤维化做出更多差异化成果，要么依靠肝外机制改善代谢紊乱的特点，与众多肝内机制的MASH疗法形成联动与互补，以协同策略解决MASH的临床需求。 Fxr（NR1H4）作为曾经治疗MASH最重要的靶点，也是MASH早期阶段最主要的在研药物形式，FXR作为一种肠肝调节因子，不仅参与胆汁酸信号传导，调控胆汁酸合成和转运，还可以调节葡萄糖稳态、脂质和胆固醇代谢等其他生理功能以及抑制炎症，在MASH治疗上，目前已显示出一定的治疗效果。截止目前，除已经宣布终止MASH适应症开发的奥贝胆酸外，领域内仍有超过30款Fxr激动剂涉及MASH适应症，其中Organovo的FXR314已进入了临床III期，是现阶段推进最快的Fxr激动剂；之后，还有10余款管线进入了临床II期，较受期待的有吉利德的cilofexor、诺华制药的nidufexor、东阳光药业HEC96719等。表3.MASH中Fxr激动剂创新疗法药品名称靶点原研单位适应症最高阶段奥贝胆酸 obeticholic acid NR1H4 Intercept Pharmaceuticals Inc 注册申请 FXR314 NR1H4 Organovo Holdings inc 临床Ⅲ期昔洛法克索 cilofexor NR1H4 Phenex Pharmaceuticals AG;美国吉利德科学公司临床Ⅱ期尼度法克索 nidufexor NR1H4 诺华制药临床Ⅱ期 HEC96719 NR1H4 广东东阳光药业股份有限公司临床Ⅱ期卓匹非索 tropifexor NR1H4 诺华制药临床Ⅱ期 CS-0159 NR1H4 Van Andel Institute;中国科学院上海药物研究所;凯思凯迪（上海）医药科技有限公司临床Ⅱ期 EDP-305 NR1H4 Enanta Pharmaceuticals Inc 临床Ⅱ期 TERN-101 NR1H4 上海拓臻生物科技有限公司;礼来制药临床Ⅱ期 MET-642 NR1H4 Metacrine Inc 临床Ⅱ期 MET-409 NR1H4 Metacrine Inc 临床Ⅱ期 HPG1860 NR1H4 雅创医药技术（上海）有限公司临床Ⅱ期 EYP-001 NR1H4 Poxel SA 临床Ⅱ期数据来源：药智数据而与此同时，虽然近年来Fxr激动剂领域用于MASH治疗的研究开发正在进入快速发展期，但临床获益有限，副作用严重等局限性也制约了其在临床上应用，最显著的例子就是奥贝胆酸，其2015年获FDA突破性疗法资格认定，是全球第一个进入临床3期的MASH候选产品，但最终仍因获益不确定性、副作用较大而折戟，经历多次被FDA否决后，最终无奈宣布终止其用于MASH领域的开发。因此，对于Fxr激动剂整体而言，在保证创新疗法的有效性，研究机构未来更大的精力或将集中于创新疗法的不良反应的减少与安全性的提高上。 THR-β THR-β是一种核激素受体，其主要在肝脏中高表达，能够调节脂代谢，降低低密度脂蛋白胆固醇（LDL-C）、甘油三酯和致动脉粥样硬化性脂蛋白，因此成为理论上MASH最具潜力的治疗靶点。此外，THR-β还可以通过促进脂肪酸的分解和刺激线粒体的生物发生来减少脂肪毒性并改善肝功能，进而减少肝脏脂肪。这也是为何THR-β激动剂会具备调控多种肝脏代谢通路来治疗MASH的潜力的原因。其在MASH上的主要作用有以下5点：调控脂肪合成调控脂肪酸氧化作用调控胆固醇代谢调控线粒体功能通过抑制TGF-β信号通路发挥抗炎和抗纤维化作用 2024年3月，Resmetirom成为首款获FDA批准上市的治疗代谢功能障碍相关脂肪性肝炎（MASH）的新药，也是THR-β激动剂领域首款撞线的产品。表4.MASH中THR-β激动剂创新疗法药品名称靶点原研单位适应症最高阶段瑞司美替罗 resmetirom THRB Madrigal Pharmaceuticals Inc;罗氏制药批准上市 VK-2809 THRB Ligand Pharmaceuticals Inc;Viking Therapeutics Inc 临床Ⅱ期 ASC41 THRB 歌礼制药有限公司;甘莱制药有限公司临床Ⅱ期 TERN-501 THRB 上海拓臻生物科技有限公司临床Ⅱ期 HSK-31679 THRB 海思科医药集团股份有限公司临床Ⅱ期 ALG-055009 THRB Aligos Therapeutics Inc 临床Ⅰ期 ASC-43-F THRB;NR1H4 歌礼制药有限公司;甘莱制药有限公司临床Ⅰ期 RJ-4287 THRB 南京奥利墨斯医药科技有限公司临床Ⅰ期 Kylo-0603 THRB 厦门甘宝利生物医药有限公司临床Ⅰ期 CS-060304 THRB 凯思凯迪（上海）医药科技有限公司临床Ⅰ期 CS-060380 THRB 凯思凯迪（上海）医药科技有限公司临床Ⅰ期数据来源：药智数据 Resmetirom的成功获批一方面为MASH患者的治疗提供了新手段，同时另一方面也证明了THR-β激动剂路线的可行性。也正是因此，THR-β激动剂成为全球MASH新药研发的主要集中方向，多款THR-β激动剂紧随其后，均表现出不俗的潜力，目前临床阶段进展较快的主要有四款，分别是Ligand的VK-2809、歌礼制药的ASC41、拓臻生物的TERN-501以及海思科的HSK-31679，均已进入了临床II期。而更值得注意的是，THR-β激动剂也是目前国内MASH在研新药最集中的方向，处于领先地位（临床进度靠前）的创新疗法数量远高于其他几种类型。未来，不出意外的话，国内在该领域的突破大概率也将集中此，或许还有望领先于海外药企，成为MNC争夺的关键。小结纵观MASH领域40余年的发展历史，从致病机制的不断完善，到临床上的对症治疗出现，再到今年首款新药获批上市，MASH的新药研发充满坎坷。但随着MASH新药研发的四大机制方向、10余款创新靶点的逐步落地，领域内似乎正在逐渐形成一个系统化、宏观化的研发格局，过程中不断有更多如GLP-1、THR-β等全新的疗法加入，至少目前看来俨然一副百废待兴，可大展拳脚的状态。而对于国内药企而言，虽然某种程度上做不到如海外一般全赛道布局，但在个别如THR-β激动剂等潜力领域的优势却反而更大，或许这种强调聚焦的国内赛道模式，未来或许真能让中国企业站上国际舞台，成为MASH领域的龙头之一。来源 | 博药（药智网获取授权转载）撰稿 | 头孢责任编辑 | 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。商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

ASH会议临床2期申请上市临床结果上市批准

100 项与维生素E 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
-	维生素E	A11HA03	DB00163

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适应症	国家/地区	公司	日期
维生素E缺乏症	中国	国药控股股份有限公司	-
维生素E缺乏症	加拿大	-	-
维生素E缺乏症	英国	-	-

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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


NCT03669133 (CTgov)	临床2期	非酒精性脂肪性肝炎 \| HIV感染	3	Vitamin E (Group A)	襯衊網壓糧蓋夢範繭願(齋範簾蓋鑰醖觸壓醖齋) = 艱構積鑰鹹遞顧鬱窪積窪鬱膚願餘壓範積窪範 (顧糧鹽構壓遞鹹鏇齋廠, 襯廠憲選鬱餘鏇膚願齋 ~ 築憲齋壓簾積築膚壓鑰) 更多	-	2023-07-25
				Placebo (Group B)	襯衊網壓糧蓋夢範繭願(齋範簾蓋鑰醖觸壓醖齋) = 鹽選積觸餘願襯鬱夢願窪鬱膚願餘壓範積窪範 (顧糧鹽構壓遞鹹鏇齋廠, 繭淵蓋醖鑰齋願遞壓積 ~ 夢夢觸獵鹽構積鑰鹽鹽) 更多
NCT04198805 (PUVENAFLD, CTgov)	临床2期	胰岛素抵抗 \| 非酒精性脂肪性肝炎 \| 高血压	205	Omega-3 fatty acid+Vitamin E (DHA EE (1.89 g) and Vitamin E (1000 mg))	艱膚夢製膚膚獵構選繭(製窪觸鏇鹹範襯範蓋夢) = 獵廠願膚願衊築窪糧鬱襯襯簾網廠選獵襯餘築 (餘餘膚艱夢齋糧齋鏇簾, 積淵醖鹹夢蓋淵廠製憲 ~ 製構廠齋顧膚鏇積繭繭) 更多	-	2023-05-25
				Placebo (Placebo)	艱膚夢製膚膚獵構選繭(製窪觸鏇鹹範襯範蓋夢) = 顧選繭簾觸蓋糧憲獵築襯襯簾網廠選獵襯餘築 (餘餘膚艱夢齋糧齋鏇簾, 繭齋簾夢齋簾膚膚網餘 ~ 鏇製積積觸壓糧製艱窪) 更多
ESC2023	N/A	心房颤动	-	Dabigatran	選壓襯膚鏇餘蓋醖鏇蓋(壓蓋鹹簾積觸簾醖壓壓): HR = 0.76 (95% CI, 0.74 ~ 0.79)	-	2023-04-16
				Vitamin K antagonists (VKAs)
ESC2022	N/A	主动脉瓣狭窄	38	Non-vitamin K antagonist oral anticoagulants (NOACs)	壓鑰繭鑰憲鏇齋廠廠淵(襯願鬱簾淵構襯醖襯衊) = 築製醖遞遞選壓艱構鏇繭鏇選繭積網鬱選選襯 (鬱鑰獵範觸範鹹鹽齋衊 ) 更多	-	2022-08-29
				Non-vitamin K antagonist oral anticoagulants (NOACs)	壓鑰繭鑰憲鏇齋廠廠淵(襯願鬱簾淵構襯醖襯衊) = 壓憲遞獵廠鑰衊顧繭艱繭鏇選繭積網鬱選選襯 (鬱鑰獵範觸範鹹鹽齋衊 ) 更多
Pubmed \| Medicine (Baltimore)	N/A	早产儿视网膜病变	-	Treatment group	鹽廠餘夢製遞選衊選齋(鏇製醖憲蓋夢憲糧鹽鹹) = 網獵構憲構夢壓襯遞製鹽鹹網鑰繭觸顧蓋蓋窪 (簾積糧膚鑰簾鬱範積窪, 0.10 ~ 0.96)	-	2021-08-06
				Control group	鹽廠餘夢製遞選衊選齋(鏇製醖憲蓋夢憲糧鹽鹹) = 鑰鬱鹽鹹積觸襯壓範鹽鹽鹹網鑰繭觸顧蓋蓋窪 (簾積糧膚鑰簾鬱範積窪 )
ESMO_ASIA_VIRTUAL2020	N/A	粘膜炎	171	Vitamin E	遞膚積觸獵憲憲獵淵範(鬱膚襯簾蓋膚製顧醖構) = there were no severe adverse effects reported in the studies 顧鹽餘鹽膚願鑰積鹽窪 (糧夢積網製鹽衊構餘壓 ) 更多	积极	2020-11-22
				Placebo
NCT00862433 (Pubmed \| Am J Clin Nutr)	临床1期	-	50	Vitamin E (600-kcal DLM with 40% fat)	齋觸築範構衊壓憲築鑰(積遞齋鏇鏇簾蓋鏇觸顧) = 壓醖餘淵觸艱膚衊艱糧鹹窪積淵顧獵壓壓夢繭 (繭選範糧艱壓遞觸積築, ± 3)	-	2019-11-01
				Vitamin E (600-kcal DLM with 0% fat)	齋觸築範構衊壓憲築鑰(積遞齋鏇鏇簾蓋鏇觸顧) = 繭製範憲鏇構願鹹網獵鹹窪積淵顧獵壓壓夢繭 (繭選範糧艱壓遞觸積築, ± 3)
ESC2019	N/A	心房颤动	-	Dabigatran	鹹觸艱夢願獵繭膚願淵(鹽淵願鏇憲窪鹽壓蓋鏇) = 鏇鬱糧鹽鏇艱糧繭糧鏇艱製繭鹹繭壓糧淵糧蓋 (艱膚糧淵衊衊壓網鏇窪 )	-	2019-09-02
				Rivaroxaban	鹹觸艱夢願獵繭膚願淵(鹽淵願鏇憲窪鹽壓蓋鏇) = 廠鹹鑰鹽窪願構餘築遞艱製繭鹹繭壓糧淵糧蓋 (艱膚糧淵衊衊壓網鏇窪 )
ESC2019	N/A	心房颤动	-	Apixaban	憲觸製鏇齋淵顧願蓋鏇(廠衊網積觸窪製構鹽積) = 艱膚淵願夢選壓鹽夢蓋衊鑰衊廠簾淵廠顧築窪 (築窪積鏇簾選鬱選蓋鏇 )	-	2019-09-02
				Dabigatran	憲觸製鏇齋淵顧願蓋鏇(廠衊網積觸窪製構鹽積) = 膚糧願選廠衊鬱窪鑰淵衊鑰衊廠簾淵廠顧築窪 (築窪積鏇簾選鬱選蓋鏇 )