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Ibrexafungerp for the treatment of vulvovaginal candidiasis. 伊布菌灵治疗外阴阴道念珠菌感染。
Pub Date : 2022-04-01 DOI: 10.1358/dot.2022.58.4.3381586
J. Sobel
Worldwide, effective management of vulvovaginal candidiasis (VVC) continues to serve as a major therapeutic goal with numerous unmet drug treatment challenges. After 3 decades of azole drug dominance, with few recent new antifungal agents and little progress in VVC management, the first-in-class oral triterpenoid glucan synthase inhibitor agent ibrexafungerp has emerged in the treatment of acute VVC. After reviewing existing treatment standards and unmet needs, the pharmacology, pharmacokinetics, antimicrobial activity and clinical efficacy of ibrexafungerp are reviewed in this article together with phase III clinical trial results and drug safety. The projected role and status of ibrexafungerp are reviewed together with perspectives of its future development and role in the treatment of VVC.
在世界范围内,有效治疗外阴阴道念珠菌病(VVC)仍然是一个主要的治疗目标,但仍有许多药物治疗挑战尚未得到解决。在唑类药物占据主导地位30年后,由于最近几乎没有新的抗真菌药物,VVC管理也几乎没有进展,第一种口服三萜葡聚糖合酶抑制剂ibrexafungerp已出现在急性VVC的治疗中。在回顾了现有的治疗标准和未满足的需求后,本文对ibrexafungerp的药理学、药代动力学、抗菌活性和临床疗效以及III期临床试验结果和药物安全性进行了综述。本文综述了ibrexafungerp的预期作用和现状,并对其未来发展和在VVC治疗中的作用进行了展望。
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引用次数: 2
Sotorasib: a treatment for non-small cell lung cancer with the KRAS G12C mutation. 索托拉西布:治疗KRAS G12C突变的癌症。
Pub Date : 2022-04-01 DOI: 10.1358/dot.2022.58.4.3400573
Xinting Zheng, Jiamin Luo, Wei Liu, C. Ashby, Zhe S Chen, Lizhu Lin
Sotorasib, a direct inhibitor of the enzyme Kirsten rat sarcoma viral oncogene (KRAS) with the G12C mutation, was approved by the U.S. Food and Drug Administration (FDA), as a second-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) containing the KRAS G12C mutation, on the basis of results of a phase II clinical trial (Code- BreaK100). In this article, we review the mechanism of action of KRAS G12C inhibitors and the latest clinical trials with sotorasib to provide a comprehensive understanding of its efficacy and toxicity. We also review the mechanisms that produce resistance to the KRAS G12C inhibitors and the preclinical research related to combination treatments for KRAS G12C-mutated tumors. Currently, clinical data suggests that sotorasib monotherapy has significant efficacy in NSCLC patients with the KRAS G12C mutation and tolerable toxicity, and it could represent a novel targeted therapy. Additional research will be required to delineate the mechanisms of resistance to sotorasib and determine the efficacy and safety of combination therapy for the treatment of NSCLC containing the KRAS G12C mutation.
根据II期临床试验(Code-BreaK100)的结果,Sotorasib是一种具有G12C突变的Kirsten大鼠肉瘤病毒癌基因(KRAS)酶的直接抑制剂,被美国食品药品监督管理局(FDA)批准为含有KRAS G12C突变局部晚期或转移性非小细胞肺癌(NSCLC)的二线治疗药物。在这篇文章中,我们回顾了KRAS G12C抑制剂的作用机制和索托拉西布的最新临床试验,以全面了解其疗效和毒性。我们还综述了对KRAS G12C抑制剂产生耐药性的机制,以及与KRAS G12C-突变肿瘤联合治疗相关的临床前研究。目前,临床数据表明,索托拉西布单药治疗KRAS G12C突变和可耐受毒性的NSCLC患者具有显著疗效,可能是一种新的靶向治疗方法。还需要进一步的研究来描述对索托拉西布的耐药性机制,并确定联合治疗含有KRAS G12C突变的NSCLC的疗效和安全性。
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引用次数: 4
Nemolizumab for atopic dermatitis. 奈莫单抗治疗特应性皮炎。
Pub Date : 2022-04-01 DOI: 10.1358/dot.2022.58.4.3378056
A. Labib, A. Vander Does, Gil Yosipovitch
Atopic dermatitis (AD) is a common inflammatory skin disease that has emerging treatments targeting the underlying immunological mechanism. Interleukin-31 (IL-31) is associated with the pathobiological mechanism of AD, contributing to symptoms such as dermatitis and pruritus. Nemolizumab is an anti-IL-31 receptor α-chain (IL-31RA) monoclonal antibody agent that is efficacious in improving symptoms of AD in several phase II and phase III studies in recent years. Nemolizumab demonstrates great efficacy in reducing pruritus and to a lesser degree, dermatitis associated with AD. Additionally, one advantage of nemolizumab is its quick speed of action. Adverse effects are mild and transient in nature, including exacerbation of AD, nasopharyngitis, upper respiratory tract infections, elevated creatine kinase and peripheral edema. Severe adverse effects were not common and consisted of exacerbation of AD and asthma exacerbation. Therefore, nemolizumab has the potential to be an important treatment of choice for AD given its efficacy, mild side effect profile and rapid time of onset. In this review, we examine the preclinical and clinical studies of the novel drug nemolizumab for the treatment of AD with a focus on its mechanism of action, pharmacokinetics, safety, efficacy, indications and drug interactions.
特应性皮炎(AD)是一种常见的炎症性皮肤病,针对潜在的免疫机制有新的治疗方法。白细胞介素-31 (IL-31)与AD的病理生物学机制有关,可导致皮炎、瘙痒等症状。Nemolizumab是一种抗il -31受体α-链(IL-31RA)单克隆抗体制剂,近年来在多项II期和III期研究中有效改善AD症状。Nemolizumab在减轻瘙痒和较小程度上与AD相关的皮炎方面显示出巨大的功效。此外,奈莫单抗的一个优势是其快速的作用速度。不良反应是轻微和短暂的,包括阿尔茨海默病加重、鼻咽炎、上呼吸道感染、肌酸激酶升高和周围水肿。严重的不良反应并不常见,主要包括AD加重和哮喘加重。因此,鉴于nemolizumab的疗效、轻微的副作用和快速的起效时间,它有可能成为阿尔茨海默病的重要治疗选择。在这篇综述中,我们研究了新型药物nemolizumab治疗AD的临床前和临床研究,重点关注其作用机制、药代动力学、安全性、有效性、适应症和药物相互作用。
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引用次数: 4
Tanezumab for the treatment of osteoarthritis pain. Tanezumab治疗骨关节炎疼痛。
Pub Date : 2022-04-01 DOI: 10.1358/dot.2022.58.4.3352752
F. Gondal, J. Bilal, C. Kent Kwoh
Tanezumab is a novel humanized IgG2 monoclonal antibody that works by selectively targeting, binding to and inhibiting nerve growth factor (NGF). NGF is upregulated in response to injury and inflammation, and preclinical data indicate it plays a role in pain signaling by inducing peripheral and central sensitization. Tanezumab potentially reduces sensitization and pain by blocking the interaction between NGF and the tropomyosin receptor kinase A (TrkA), and it has been studied extensively for the treatment of pain in patients with osteoarthritis (OA). In 2017, tanezumab was granted fast track designation in the U.S. for the treatment of chronic pain in patients with OA, as well as for the treatment of chronic low-back pain. This review discusses the mechanism of action, preclinical data and phase I, II and III studies of efficacy and safety of tanezumab in patients with OA.
Tanezumab是一种新型人源化IgG2单克隆抗体,通过选择性靶向、结合和抑制神经生长因子(NGF)发挥作用。NGF在损伤和炎症反应中上调,临床前数据表明,它通过诱导外周和中枢敏化在疼痛信号传导中发挥作用。Tanezumab通过阻断NGF和原肌球蛋白受体激酶A(TrkA)之间的相互作用,有可能减少致敏和疼痛,它已被广泛研究用于治疗骨关节炎(OA)患者的疼痛。2017年,坦珠单抗在美国被授予快速通道指定,用于治疗OA患者的慢性疼痛,以及治疗慢性腰痛。这篇综述讨论了坦珠单抗治疗OA患者的作用机制、临床前数据以及疗效和安全性的I、II和III期研究。
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引用次数: 6
Anamorelin for cancer cachexia. Anamorelin治疗癌症恶病质。
Pub Date : 2022-03-01 DOI: 10.1358/dot.2022.58.3.3381585
K. Nishie, Seiichi Sato, M. Hanaoka
Cancer anorexia-cachexia syndrome is a multifactorial condition characterized by significant weight loss due to muscle loss. It is associated with functional impairment, changes in body composition and nutritional disorders. Ghrelin receptors are involved in the release of growth hormone (GH) in the pituitary gland and increase appetite via the hypothalamus. The secretion of GH from the pituitary gland stimulates the liver to secrete insulin-like growth factor 1 (IGF-1), which promotes muscle protein synthesis. Anamorelin is a ghrelin receptor agonist used to treat cancer cachexia. It promotes GH secretion via ghrelin receptor activation and increases appetite, resulting in increased muscle mass and weight. Clinical trials of anamorelin have demonstrated a significant increase in lean body mass index, improved cachexia and no significant increase in serious adverse events. The present review describes the processes leading to the approval of anamorelin in Japan, focusing on pharmacology, metabolism, efficacy, safety and clinical trials.
癌症厌食恶病质综合征是一种多因素疾病,其特征是肌肉减少导致体重显著减轻。它与功能损伤、身体成分变化和营养障碍有关。Ghrelin受体参与垂体中生长激素(GH)的释放,并通过下丘脑增加食欲。垂体分泌GH刺激肝脏分泌胰岛素样生长因子1(IGF-1),促进肌肉蛋白质合成。Anamorelin是一种用于治疗癌症恶病质的胃促生长素受体激动剂。它通过促生长素受体激活促进生长激素分泌,并增加食欲,从而增加肌肉质量和体重。anamorelin的临床试验表明,瘦体重指数显著增加,恶病质改善,严重不良事件没有显著增加。本综述介绍了安那莫林在日本获得批准的过程,重点介绍了药理学、代谢、疗效、安全性和临床试验。
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引用次数: 6
An update on romiplostim for treatment of acute radiation syndrome. 罗普司汀治疗急性放射综合征的最新进展。
Pub Date : 2022-03-01 DOI: 10.1358/dot.2022.58.3.3367994
Vijay K. Singh, T. Seed
Detonation of an improvised nuclear weapon, or a radiological dispersal device by terrorists, or an unintended radiological/nuclear accident in populated areas would result in a mass casualty scenario with radiation exposures of different severities. Such incidences are perceived as national security threats of major consequences. Acute radiation syndrome (ARS) is triggered by an exposure to a high dose of penetrating ionizing radiation during a short time window. In humans, moderate exposure to 2 to 4 Gy of ionizing radiation results in clinically manageable hematopoietic ARS (H-ARS), characterized by severe depletion of vital blood cells and bone marrow progenitors. Since 2015, the United States Food and Drug Administration (U.S. FDA) has approved four radiation medical countermeasures for H-ARS following the Animal Rule; namely, Neupogen, Neulasta, Leukine and Nplate (romiplostim). Here, we briefly present the treatment modalities for H-ARS. We have discussed the latest FDA-approved agent, romiplostim, as a treatment modality for H-ARS. The nature of this agent and the preclinical and clinical work that preceded its FDA approval as a radiation medical countermeasure are discussed, as are the development and use of related thrombopoietic agents for the treatment of radiation-exposed victims.
恐怖分子引爆简易核武器或放射性扩散装置,或在人口稠密地区发生意外的放射性/核事故,都会造成大规模伤亡,辐射暴露程度不同。此类事件被视为对国家安全的重大威胁。急性辐射综合征(ARS)是由在短时间窗口内暴露于高剂量穿透性电离辐射引发的。在人类中,适度暴露于2-4 Gy的电离辐射会导致临床上可控制的造血ARS(H-ARS),其特征是重要血细胞和骨髓祖细胞的严重耗竭。自2015年以来,美国食品药品监督管理局(U.S.FDA)根据动物规则批准了四种针对H-ARS的辐射医疗对策;即Neupogen、Neulasta、Leukine和Nplate(romipostim)。在这里,我们简要介绍了H-ARS的治疗方式。我们已经讨论了美国食品药品监督管理局批准的最新药物romipostim,作为H-ARS的一种治疗方式。讨论了这种制剂的性质以及在美国食品药品监督管理局批准其作为辐射医疗对策之前的临床前和临床工作,以及用于治疗辐射暴露受害者的相关血小板生成素制剂的开发和使用。
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引用次数: 9
Idecabtagene vicleucel for relapsed/refractory multiple myeloma: a review of recent advances. Idecbtagene vicleucel治疗复发/难治性多发性骨髓瘤:最新进展综述。
Pub Date : 2022-03-01 DOI: 10.1358/dot.2022.58.3.3381592
W. Tu, Ya-juan Xiao, Yadong Wang, R. Luo, Zhe S Chen
The introduction of new classes of drugs for the treatment of multiple myeloma (MM) in the past 2 decades, such as proteasome inhibitors, immunomodulators and anti-CD38 monoclonal antibodies, coupled with autologous stem cell transplantation, has approximately doubled the 5-year survival rate of MM patients. However, the patients eventually relapse and/or become resistant to the drugs and treatment. The recent emergence of anti-B-cell maturation antigen (BCMA) therapies, especially chimeric antigen receptor T-cell (CAR-T) immunotherapy targeting BCMA, holds great prospect in MM treatment. In this article, we review in detail the advances of idecabtagene vicleucel (ide-cel, bb-2121), the first CAR-T therapy targeting BCMA for treating relapse or refractory MM approved by the U.S. Food and Drug Administration (FDA) in 2021, including the preclinical study and phase I and II clinical trials. Also, it is predicted in this review that despite its amazing clinical efficacy and relatively lower toxicity, a lot of challenges and unsolved problems for ide-cel therapy remain in the way ahead.
在过去的20年里,用于治疗多发性骨髓瘤(MM)的新型药物的引入,如蛋白酶体抑制剂、免疫调节剂和抗CD38单克隆抗体,再加上自体干细胞移植,使MM患者的5年生存率大约翻了一番。然而,患者最终会复发和/或对药物和治疗产生耐药性。最近出现的抗B细胞成熟抗原(BCMA)疗法,特别是针对BCMA的嵌合抗原受体T细胞(CAR-T)免疫疗法,在MM治疗中具有很大的前景。在这篇文章中,我们详细回顾了idecabtagene vicleucel(ide cel,bb-2121)的进展,包括临床前研究和I期和II期临床试验,这是美国食品药品监督管理局(FDA)于2021年批准的第一种针对BCMA的CAR-T疗法,用于治疗复发或难治性MM。此外,这篇综述预测,尽管其具有惊人的临床疗效和相对较低的毒性,但ide-cel治疗仍有许多挑战和未解决的问题。
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引用次数: 1
Eptacog beta, a novel recombinant factor VIIa, for the treatment of hemophilia. Eptacog β,一种新的重组因子VIIa,用于治疗血友病。
Pub Date : 2022-03-01 DOI: 10.1358/dot.2022.58.3.3381593
Nathan W. Watson, H. Al‐Samkari
Hemophilia A and B are X-linked hereditary bleeding disorders due to factor VIII (FVIII) or factor IX (FIX) deficiency, respectively. Major advancements have been made in the care of patients with hemophilia, yet the development of inhibitors to infused FVIII or FIX continues to be a formidable challenge. The current first-line therapy for acute bleeding episodes in patients diagnosed with inhibitors are bypassing agents including activated prothrombin complex concentrates (aPCCs) and recombinant factor VIIa (rFVIIa). Eptacog beta (SevenFact; LFB Biotechnologies, Hema Biologics) is a new rFVIIa product produced via expression in the milk of transgenic rabbits. This emerging platform has demonstrated numerous cost advantages to traditional cell culture systems including a better ability to scale up production and better protein yields. Eptacog beta is currently approved by the U.S. Food and Drug Administration (FDA) for the on-demand control of bleeding episodes in patients with hemophilia aged 12 to 75 with inhibitors. A potential future expansion of its current label could occur given the recent completion of two major phase III clinical trials evaluating its efficacy in children as well as its use for perioperative management. In this paper, we describe the preclinical and clinical literature documenting the development of eptacog beta and discuss its current and future application for the management of patients with hemophilia and inhibitors.
血友病A和B分别是由因子VIII(FVIII)或因子IX(FIX)缺乏引起的X连锁遗传性出血性疾病。血友病患者的护理取得了重大进展,但开发输注FVIII或FIX的抑制剂仍然是一个巨大的挑战。目前,对被诊断为使用抑制剂的患者急性出血发作的一线治疗是绕过药物,包括活化凝血酶原复合物浓缩物(aPCCs)和重组因子VIIa(rFVIIa)。Eptacogβ(SevenFact;LFB Biotechnologies,Hema Biologics)是一种新的rFVIIa产品,通过在转基因兔的乳汁中表达产生。这个新兴的平台已经证明了传统细胞培养系统的许多成本优势,包括更好的规模化生产能力和更好的蛋白质产量。Eptacogβ目前已获得美国食品药品监督管理局(FDA)的批准,用于使用抑制剂按需控制12至75岁血友病患者的出血发作。鉴于最近完成了两项主要的III期临床试验,评估其在儿童中的疗效以及用于围手术期管理,其目前的标签可能会在未来扩大。在本文中,我们描述了记录庚酮β发展的临床前和临床文献,并讨论了其目前和未来在血友病患者和抑制剂治疗中的应用。
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引用次数: 0
New product intros [somapacitan, tezepelumab (first-in-class)] 新产品介绍[somapacitan, tezepelumab (first-in-class)]
Pub Date : 2022-01-01 DOI: 10.1358/dot.2022.58.2.3417138
Y. Gao
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引用次数: 0
New product intros [bebtelovimab, levoketoconazole] 新产品介绍[贝特洛维单抗,左旋酮康唑]
Pub Date : 2022-01-01 DOI: 10.1358/dot.2022.58.3.3421337
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引用次数: 0
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Medicamentos de actualidad. Drugs of today
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