A Phase 1b Study of the Multi-Kinase Inhibitor Regorafenib in Combination With the BCL-2 Inhibitor Venetoclax Plus Azacitidine in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This phase Ib trial tests the safety, side effects, best dose and effectiveness of regorafenib in combination with venetoclax and azacitidine in treating patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Regorafenib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps to slow or stop the spread of cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. Giving regorafenib in combination with venetoclax and azacitidine may be safe, tolerable and/or effective in treating patients with relapsed or refractory AML.

开始日期2025-03-20

申办/合作机构

City of Hope National Medical Center

[+1]

NCT06563999 / Not yet recruiting临床2期IIT

Neoadjuvant Umbrella Trial Directed by Next Generation Sequencing for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations (Without EGFR Sensitizing Mutations)

This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.

开始日期2024-12-01

申办/合作机构

中山大学

NCT06575725 / Not yet recruiting临床2期

A Phase 2 Study of Botensilimab, Balstilimab and Regorafenib in Patients With Microsatellite Stable Colorectal Cancer

This phase II trial studies how well the combination of botensilimab, balstilimab and regorafenib works compared to botensilimab and balstilimab in treating patients with microsatellite stable colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Regorafenib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps to slow or stop the spread of tumor cells. The combination of botensilimab, balstilimab and regorafenib or botensilimab and balstilimab may be a safe and effective treatment for advanced or metastatic microsatellite stable colorectal cancer.

开始日期2024-11-01

申办/合作机构

Hope Medical Center

[+1]

100 项与 TrkA 相关的临床结果

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100 项与 TrkA 相关的转化医学

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0 项与 TrkA 相关的专利（医药）

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6,296

项与 TrkA 相关的文献（医药）

2024-12-01·Molecular biology reports

Neurotrophin growth factors and their receptors as promising blood biomarkers for Alzheimer’s Disease: a gene expression analysis study

Article

作者: Sayad, Arezou ; Taheri, Mohammad ; Zaboli Mahdiabadi, Morteza ; Rezazadeh, Maryam ; Sabaie, Hani ; Mazhari, Seyed Amirhossein ; Gharesouran, Jalal ; Shirvani-Farsani, Zeinab ; Sharifi-Bonab, Mirmohsen ; Asadi, Mohammad Reza

BACKGROUND:

Alzheimer's disease (AD) is a multifaceted neurological ailment affecting more than 50 million individuals globally, distinguished by a deterioration in memory and cognitive abilities. Investigating neurotrophin growth factors could offer significant contributions to understanding AD progression and prospective therapeutic interventions.

METHODS AND RESULTS:

The present investigation collected blood samples from 50 patients diagnosed with AD and 50 healthy individuals serving as controls. The mRNA expression levels of neurotrophin growth factors and their receptors were measured using quantitative PCR. A Bayesian regression model was used in the research to assess the relationship between gene expression levels and demographic characteristics such as age and gender. The correlations between variables were analyzed using Spearman correlation coefficients, and the diagnostic potential was assessed using a Receiver Operating Characteristic curve. NTRK2, TrkA, TrkC, and BDNF expression levels were found to be considerably lower (p-value < 0.05) in the blood samples of AD patients compared to the control group. The expression of BDNF exhibited the most substantial decrease in comparison to other neurotrophin growth factors. Correlation analysis indicates a statistically significant positive association between the genes. The ROC analysis showed that BDNF exhibited the greatest Area Under the Curve (AUC) value of 0.76, accompanied by a sensitivity of 70% and specificity of 66%. TrkC, TrkA, and NTRK2 demonstrated considerable diagnostic potential in distinguishing between cases and controls.

CONCLUSION:

The observed decrease in the expression levels of NTRK2, TrkA, TrkC, and BDNF in AD patients, along with the identified associations between specific genes and their diagnostic capacity, indicate that these expressions have the potential to function as biomarkers for the diagnosis and treatment of AD.

2024-12-01·JOURNAL OF ETHNOPHARMACOLOGY

Targeting TRPV1 signaling: Galangin improves ethanol-induced gastric mucosal injury

Article

作者: Yi, Guohui ; Wang, Zhongtao ; Wang, Yan ; Lin, Kaiwen ; Feng, Faming ; Yu, Xiaodan ; Liu, Xiaofei ; Wang, Erhao ; Zhang, Xueer

ETHNOPHARMACOLOGICAL RELEVANCE:

Galangin, a bioactive compound extracted from Alpinia officinarum Hance (Zingiberaceae), a plant with significant ethnopharmacological importance, has been used for thousands of years as a spice, condiment, and medicinal agent for various conditions, including gastrointestinal disorders. Although there is evidence suggesting its potential to improve gastric ulcers, the molecular mechanisms underlying its anti-ulcer properties are not fully understood.

OBJECTIVE:

of the Study: This study aimed to investigate the effects of galangin on ethanol-induced acute gastric mucosal injury (AGMI) in mice and elucidate its molecular mechanisms.

MATERIALS AND METHODS:

Sixty BALB/c mice were randomly assigned into two main groups: a normal control group (n = 10) and an ethanol-induced group (n = 50). After establishing the AGMI model in mice using a combination of 40% ethanol and anhydrous ethanol, the ethanol-induced group was further subdivided into five subgroups (n = 10): an omeprazole control group (20 mg/kg), an untreated ethanol group, and three treatment groups receiving high-dose (50 mg/kg) or low-dose (25 mg/kg) galangin or capsazepine (CPZ, 2 mg/kg). The protective effects of galangin were evaluated through mucosal injury indices, hematoxylin and eosin staining, and quantification of inflammatory markers (IL-1β, IL-6, IL-8, and TNF-α). Oxidative stress levels and matrix metalloproteinase activity were measured using specific assay kits. Molecular docking was conducted to assess the binding affinity of galangin to key proteins within the transient receptor potential vanilloid 1 (TRPV1) pathway. Real-time fluorescence quantitative PCR (qPCR) was used to determine mRNA expression levels of TRPV1, calmodulin (CaM), substance P (SP), and CGRP in gastric tissues. Protein expression levels of TRPV1, nerve growth factor (NGF), tropomyosin receptor kinase A (TRKA), transforming growth factor beta (TGF-β), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) were assessed through Western blot analysis. In cellular experiments, Culture of Human Gastric Epithelial Cells (GES-1) were treated with various concentrations of galangin after 7% ethanol induction. Cell proliferation, apoptosis, and migration were evaluated using Hoechst 33258 staining and transwell migration assays. TRPV1 protein expression was detected using immunofluorescence, and the expression levels of Bcl-2, BCL2-Associated X (BAX), and Caspase-3 were quantified by qPCR. Additionally, specific probe kits were used to measure intracellular calcium ions (Ca²⁺) and mitochondrial membrane potential.

RESULTS:

The findings indicate that galangin significantly improved mucosal pathology by reducing ulcer indices and inflammatory levels, while enhancing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) concentration. Galangin also reduced matrix metalloproteinase-2 (MMP-2), m metalloproteinase-9 (MMP-9) levels, promoting mucosal repair. At the cellular level, galangin decreased intracellular calcium ion concentration and mitigated the decline in mitochondrial membrane potential, enhance the restoration of mucosal cells, increased migration and proliferation, and reduced apoptosis. Molecularly, galangin demonstrated favorable binding to TRPV1, NGF, TRKA, TGF-β, COX-2, and NF-κB, and reversed the elevated expression of these proteins. Additionally, galangin downregulated the mRNA expression of TRPV1, CaM, SP, CGRP, BAX, and Caspase-3 in gastric tissues/cells, while upregulating Bcl-2 mRNA expression.

CONCLUSION:

Galangin mitigates AGMI by inhibiting the overactivation of the TRPV1 pathway, thereby blocking aberrant signal transduction. This study suggests that galangin has therapeutic potential against ethanol-induced AGMI and may be a viable alternative for the treatment of alcohol-induced gastric mucosal injuries.

2024-11-01·NEUROSCIENCE

Cisplatin induced alterations in nociceptor developmental trajectory elicits a TrkA dependent platinum-based chemotherapy induced neuropathic pain

Article

作者: Da Vitoria Lobo, Marlene ; Tomblin, Lucy ; Philip Hulse, Richard ; Hardowar, Lydia ; Valentine, Tameille ; Sharma, Dhyana ; Corbett, Jack ; Elphick-Ross, Jasmine ; Owen, Beccy ; Skeen, Oliver

Cisplatin-based chemotherapy is a common treatment for paediatric cancer. Unfortunately, cisplatin treatment causes neuropathic pain, a highly prevalent adverse health related complication in adult childhood cancer survivors. Due to minimal understanding of this condition, there are currently no condition tailored analgesics available. Here we investigated an alteration in nociceptor maturation that results in neuronal sensitisation and manifestation of cisplatin induced survivorship pain in a TrkA dependent manner. Cisplatin was administered (i.p. 0.1 mg/kg Postnatal day 14 and 16) to neonatal male and female Wistar rats and nociceptive behavioural assays were performed. In vitro studies utilised isolated neonatal dorsal root ganglia sensory neurons treated with cisplatin (5 μg/ml) to elucidate impact upon nociceptor activation and neurite growth, in combination with TrkA inhibition (GW441756 10 nM and 100 nM). Cisplatin treated male and female neonatal Wistar rats developed a delayed but lasting mechanical and heat hypersensitivity. Cisplatin administration led to increased TrkA expression in dorsal root ganglia sensory neurons. Nerve growth factor (NGF) induced TrkA activation led to sensory neuritogenesis and nociceptor sensitisation, which could be prevented through pharmacological TrkA inhibition (GW441756 either s.c. 100 nM or i.p. 2 mg/kg). Administration of TrkA antagonist suppressed cisplatin induced TRPV1 mediated nociceptor sensitisation and prevented cisplatin induced neuropathic pain. These studies provide greater understanding of the underlying mechanisms that cause cisplatin induced childhood cancer survivorship pain and allowing identification of potential therapeutic targets.

218

项与 TrkA 相关的新闻（医药）

2024-09-16

·药智网

当沪指失守2800点，这家Biotech已经涨超60%

在全球市场环境的影响下，沪指再次失守2800点。依旧处在“寒冬”中的A股医药股更是惨不忍睹。6月以来，截至9月12日，A股495只医药股中，只有50只实现股价正增长，占比仅10.1%，其中涨幅超过20%的医药股，仅有11家。然而，在不经意间，低调的诺诚健华从6月份起，股价开启单边上涨模式，从6月份低点7.28元/股，涨至最高12元/股，上涨幅度超过60%。诺诚健华何以成为2024年下半年的黑马，与其他在“寒风”中瑟瑟发抖的Biotech又有何不同？超额完成业绩目标一款超级单品对一家Biotech有多重要，诺诚健华给出了很好的答案。 2024年上半年，诺诚健华实现营业收入4.2亿元，同比增长11.17%；归母净利润-2.62亿元，亏损大幅收窄37.6%。其联合创始人、董事长兼首席执行官崔霁松博士将增长的原因归功于“商业化业绩超额完成既定目标，收入大幅增加。” 诺诚健华的商业化产品有两款，分别是奥布替尼和Tafasitamab。作为绝对主力，奥布替尼上半年销售收入4.18亿元，同比增加29.97%，其中二季度销售收入2.53亿元，同比增长49%，增长势头明显。由于核心产品商业化进展顺利，诺诚健华自信地将2024年全年奥布替尼销售收入从至少同比增长30%调高至35%。 2020年12月获批上市的奥布替尼是国内第三款，国产第二款BTK抑制剂，获批的适应症包括慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）、套细胞淋巴瘤（MCL）以及边缘区淋巴瘤（MZL），并全部进入国家医保。其中，MZL是中国第二常见的非霍奇金淋巴瘤（NHL），奥布替尼是国内首个且唯一获批针对复发或难治性MZL适应症的BTK抑制剂，市场需求广阔。 2021年-2023年，奥布替尼销售额逐年增长，分别为2.56亿元、5.66亿元、6.72亿元，其实2023年增速已大幅放缓，但随着新适应商业化进展顺利，2024年又重回高速发展轨道。当然，奥布替尼面对的竞争也十分激烈。2023年，阿斯利康的阿卡替尼获NMPA批准，国内获批的BTK抑制剂增加到4款。其中，百济神州的泽布替尼在与曾经的药王，伊布替尼对比的大规模头对头研究中完胜，令其有望快速取代伊布替尼的市场地位。诺诚健华虽然未就奥布替尼进行“头对头”试验以证明其拥有更好的药效，但其采用单环母核设计，这种设计可以提升药物的选择性，降低脱靶副作用。公开数据显示，奥布替尼不良事件发生率低于伊布替尼、阿卡替尼和泽布替尼。正因为其独特的安全性优势，奥布替尼在自身免疫性疾病的治疗领域相比其他BTK抑制剂更有优势。目前，治疗ITP的中国注册性III期临床试验正在进行；其他自免疾病包括SLE、MS、NMOSD的II期临床试验也取得了积极进展。更多适应症的获批，尤其是自免治疗领域适应症取得突破，能够让奥布替尼不断获得增长动力，甚至有望实现弯道超车。诺诚健华在自免领域的开发策略图片来源：诺诚健华半年报此外，得益于奥布替尼销售额的增长以及营业收入结构的改变，2022年-2024年上半年，诺诚健华毛利率分别为77.07%、82.61%、85.67%，连续增长。 5-6款创新药即将上市毫无疑问，奥布替尼是一款具有“Pipeline in a drug”潜力的产品，仅一款奥布替尼就为诺诚健华带来了一整个研发管线。同时，与仅靠一款产品“单腿走路”的创新药企不同，诺诚健华早早地就布局了一系列差异化的研发管线，并持续稳步推进，多款产品蓄势待发，预计将在未来3-5年推动5-6款创新药上市。在研发管线布局上，诺诚健华有着相当清晰的规划，即聚焦具有广阔市场空间的肿瘤与自身免疫性疾病领域，坚持源头创新与差异化竞争。在血液瘤领域，诺诚健华以奥布替尼为核心，加上其他在研药物（如Tafasitamab、ICP-248、ICP-B02、ICP-490、ICP-B05等），目标是通过单药或联合疗法覆盖NHL、MM及白血病全领域，成为血液瘤领域的领导者。其中，Tafasitamab是诺诚健华于2021年8月从Incyte公司引进，其用于复发或难治性DLBCL（弥漫性大B细胞淋巴瘤）已在美国和欧洲获批上市，并于2022年底在香港、海南获批使用。2024年6月，Tafasitamab联合疗法的BLA获得CDE受理并纳入优先审评，预计将于2025年上半年获得批准。在自免领域，针对B细胞信号通路异常及T细胞通路异常的自身免疫性疾病，诺诚健华布局了多个全球前沿靶点，包括奥布替尼、ICP-332、ICP-488、ICP-B02等。其中，ICP-332是一款新型TYK2抑制剂，在治疗中重度特应性皮炎（AD）的II期临床中展现了极佳的临床数据，在疗效优于多款已获批药物的同时，具有优异的安全性，是诺诚健华在自免领域潜在的王牌产品。其AD的III期临床试验预计将于2024年第四季度启动，并启动白癜风的临床试验。在实体瘤领域，诺诚健华通过靶向治疗和肿瘤免疫方法的结合，不断扩充实体瘤疾病在研管线，包括潜在同类最佳药物ICP-723，以及早期管线，潜在的基石疗法ICP-189、ICP-B05等。其中，ICP-723(Zurletrectinib)是第二代TRK抑制剂，不仅能够有效抑制TRK家族中的TRKA、TRKB、TRKC，而且可以克服第一代TRK抑制剂的耐药性，为接受第一代TRK抑制剂后耐药的患者带来希望。目前该药已进入新药上市申请准备阶段（pre-NDA），预计在2025年初递交NDA。自免及实体瘤领域产品管线图片来源：诺诚健华半年报随着越来越多的研发管线进入临床后期，诺诚健华的研发投入也逐年增加，2024年上半年，研发费用4.21亿元，同比增长16.67%。虽然研发费用不菲，但诺诚健华的现金储备在创新药资本“寒冬”中显得十分亮眼。截至2024年上半年，诺诚健华剩余现金和其他金融资产80亿元，强劲的现金流有助于其加速全球临床试验开发，并投资有竞争力的产品管线。这些现金储备也将支持在研产品商业化，随着未来5-6款创新药商业化的成功推进，带来新的业绩增长点，企业经营也将步入正向循环。出海，Biotech的必答题从Biotech迈向Biopharma的过程中，创新是基础，国际化则是加速剂。百济神州公布的半年报显示，2024年上半年，同为BTK抑制剂的百悦泽（泽布替尼）全球销售额超过11亿美元，同比增长122%，是奥布替尼的19倍，其中美国贡献了59.03亿元，占比73.8%。一款国产创新药的成功出海，意味着身价的暴涨。在国内，泽布替尼的医保价为5440元（80毫克，64粒）。相比之下，其在美国的价格为15264美元（80毫克，120粒），折算成人民币大概是国内售价的10倍。不仅是泽布替尼，君实生物的特瑞普利单抗在国内PD-1内卷下售价为1912.96元/瓶，但相同规格产品在美国上市后售价高达8892.03美元/瓶，是国内售价的33倍。国内创新药“出海”后身价暴增，主要是因为海外市场，尤其是美国市场拥有更强的支付能力。据西南证券数据，2018年，美国总医疗费用支出是中国的16倍，人均医疗费用支出是中国的44倍。2022年，中美医疗费用支出仍存在14倍的差距，人均医疗费用仍有42倍的差距。因此，对于中国创新药企尤其是Biotech而言，“出海”已经不是一个选择题，而是一个必答题。与百济神州类似，诺诚健华同样具备国际化基因，主要管理团队成员拥有美国默克、辉瑞、葛兰素史克、百时美施贵宝、强生公司等大型跨国药企的资深工作经验，兼具国际创新视野与深刻的行业洞察。虽然与Biogen的合作遭遇挫折，但诺诚健华全球化的步伐并未停止。核心产品奥布替尼已在新加坡获批用于治疗MCL，同时FDA已授予该药品适用于R/R MCL的突破性疗法认定，预计2024年向美国FDA递交NDA上市申请；潜力产品ICP-248已于2024年1月在美国获批IND，并已启动临床试验；王牌管线ICP-332的IND也于2024年6月获FDA批准。国际化是诺诚健华战略目标，也是其发展的必经之路，通过创新药“出海”，不仅可以提升该产品在全球市场的表现，还能反哺其国内持续创新的能力。虽然“出海”之路依然面临诸多困难和挑战，但手握巨额现金的诺诚健华拥有更多的试错成本和时间。结语诺诚健华清晰的发展蓝图让未来充满了确定性，也正因此，获得了资本更多的青睐。参考资料： 1.诺诚健华、百济神州年报、季报，官网 2.《BD越玩越花，出海的泡沫能维持多久》，新浪医药，2024年08月06日 3.《5款中国创新药在美定价高于国内30倍，为何国产药出海后更贵了？》，凤凰新闻，2024年01月03日声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 史密斯转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

上市批准医药出海财报

2024-09-10

·mobihealthnews

Google DeepMind unveils AlphaProteo for AI drug design

Google DeepMind announced the launch of AlphaProteo, an AI system to help biological and health researchers design novel, high-strength proteins that bind to target molecules with accuracy and strength. AlphaProteo was trained on the Protein Data Bank (PDB) that enables breakthroughs in science and education by providing access and tools for exploration, visualization and analysis of experimentally-determined 3D structures from the PDB archive. Due to the structure of a target molecule and a set of favorite binding locations on that molecule, AlphaProteo creates a candidate protein that binds to the target. The tech giant said binders have the potential to open new areas of research in drug development and diagnostic biosensors. "AlphaProteo can generate new protein binders for diverse target proteins, including VEGF-A, which is associated with cancer and complications from diabetes. This is the first time an AI tool has been able to design a successful protein binder for VEGF-A," the Protein Design and Wet Lab teams at Google DeepMind said in a blog post. "AlphaProteo also achieves higher experimental success rates and three to 300 times better binding affinities than the best existing methods on seven target proteins we tested." To test AlphaProteo, the AI's developers designed binders for various target proteins, including "two viral proteins involved in infection, BHRF1 and SARS-CoV-2 spike protein receptor-binding domain, SC2RBD, and five proteins involved in cancer, inflammation and autoimmune diseases, IL-7Rɑ, PD-L1, TrkA, IL-17A and VEGF-A." The binding success rate for one viral target, BHRF1, was 88%, on average, ten times higher than traditional methods. The Google DeepMind web lab team worked with outside research groups, including researchers at the Francis Crick Institute, where data confirmed that AlphaProteo binders prevented SARS-CoV-2 from infecting human cells. AlphaProteo demonstrated that it could reduce the time required for initial experiments involving protein binders for various uses. However, despite the breakthroughs, the researchers noted that the AI system has limitations. For example, AlphaProteo did not generate successful binders for TNFa, a protein associated with autoimmune diseases such as rheumatoid arthritis. "We selected TNFɑ to robustly challenge AlphaProteo, as computational analysis showed that it would be extremely difficult to design binders against. We will continue to improve and expand AlphaProteo's capabilities with the goal of eventually addressing such challenging targets," the authors wrote. The AlphaProteo research team plans to work with the scientific community to observe AlphaProteo's impact on other biological problems to understand its limitations further. Additionally, the team has been exploring its drug design use at Isomorphic Labs. THE LARGER TREND In June, Google Research and Google DeepMind released a paper announcing the creation of a new LLM for drug discovery and therapeutic development dubbed Tx-LLM, fine-tuned from Med-PaLM 2. The tech giant's Med-PaLM 2 is a generative AI technology that uses Google's LLMs to answer medical questions. In May, a study performed by Google Research in collaboration with Google DeepMind showed that the tech giant expanded the capabilities of its AI models for Med-Gemini-2D, Med-Gemini-3D and Med-Gemini Polygenic. Google said it fine-tuned Med-Gemini capabilities using histopathology, dermatology, 2D and 3D radiology, genomic and ophthalmology data. In 2023, Google released MedLM, two foundational models built off Med-PaLM 2, designed to answer medical questions, generate insights from unstructured data and summarize medical information. The company said that through piloting its LLMs with healthcare organizations, it has learned the most effective AI models are designed to address specific use cases. As a result, the large model of MedLM is made to address complex tasks, while the other is a medium model that can be fine-tuned and scaled across various tasks. The HIMSS Healthcare Cybersecurity Forum is scheduled to take place October 31-November 1 in Washington, D.C. Learn more and register.

蛋白降解靶向嵌合体

2024-08-28

·美通社

美国食品药品监督管理局批准因美纳癌症生物标志物检测试剂盒及其两项伴随诊断适应症，用于快速匹配患者的靶向治疗

TruSight Oncology Comprehensive 是美国食品药品监督管理局批准的首款可上市的全景变异分析体外诊断试剂盒，具备泛癌种伴随诊断功能 500 多种基因生物标志物检测为患者提供了更精准的肿瘤诊断及治疗美国加利福尼亚州圣迭戈 2024年8月28日 /美通社/ -- 2024年8月27日，全球基因测序和芯片技术的领导者因美纳（纳斯达克股票代码：ILMN）宣布，美国食品药品监督管理局（FDA）批准了其体外诊断产品（IVD） TruSight™ Oncology (TSO) Comprehensive检测试剂盒及其首批两种伴随诊断（CDx）适应症。该产品单次检测可以覆盖500多个基因对患者的实体瘤进行分析，有助于提高发现免疫肿瘤生物标志物或临床可操作生物标志物的可能性，从而确定靶向治疗方案或临床试验入组。TSO Comprehensive作为一项伴随诊断检测产品已获得美国FDA批准，用于识别神经营养酪氨酸受体激酶（NTRK）基因融合阳性的成人和儿童实体瘤患者，在临床指导下，这些患者可能从拜耳公司的VITRAKVI ® （拉罗替尼）治疗中获得改善。该检测还被批准用于识别局部晚期或转移性转染重排（RET）融合阳性非小细胞肺癌（NSCLC）成人患者，在临床指导下，这些患者可能会从礼来公司的RETEVMO ® （塞普替尼）治疗中获得改善。 jwplayer.key="3Fznr2BGJZtpwZmA+81lm048ks6+0NjLXyDdsO2YkfE=" jwplayer('myplayer1').setup({file: 'https://mma.prnasia.com/media2/2491224/video.mp4', image: 'https://mma.prnasia.com/media2/2491224/video.mp4?p=medium', autostart:'false', stretching : 'uniform', width: '512', height: '288'}); "FDA批准TruSight Oncology Comprehensive试剂盒及其伴随诊适应症是我们肿瘤学领域客户以及肿瘤临床专家群体期待已久的里程碑事件。"因美纳首席商务官Everett Cunningham表示，"我们致力于与拜耳、礼来等行业领先的企业合作，推动癌症诊断的发展，帮助更多患者获得精准肿瘤治疗。" 伴随诊断检测可以确定患者的肿瘤是否携带特定的基因变化或生物标志物，从而成为治疗的靶点，帮助确定患者是否应该接受治疗。大多数伴随诊断检测只针对一种类型的癌症，但TSO Comprehensive检测产品的NTRK伴随诊断试剂盒已被批准用于各类实体瘤适应症，有助于最大限度地从每位患者的样本中找到可用于临床干预的信息。在大多数实体瘤类型中，NTRK基因融合较为罕见（约为0.1%-0.3%），由于这些基因可以与不同的伴侣基因发生融合，其中许多伴侣基因以前都是未知的，因而给检测增加了难度。TSO Comprehensive还能检测RNA，进而能识别所有三种NTRK基因融合（NTRK1、NTRK2和NTRK3）的已知和新型融合伴侣基因。拜耳公司的VITRAKVI（拉罗替尼）是一种高选择性TRK抑制剂，已被批准用于治疗TRK融合癌症患者。非小细胞肺癌是最常见的肺癌类型之一，也是全球癌症相关死亡的主要原因。非小细胞肺癌相关可用的生物标志物种类繁多，因此需要进行广泛的分子图谱分析，以全面了解患者的病情，更好地指导临床治疗。RET基因融合阳性非小细胞肺癌的致癌激活是非小细胞肺癌的主要驱动因素，发生率达2%。礼来公司的RETEVMO（塞普替尼）是一种高选择性、强效的RET激酶抑制剂，适用于局部晚期或转移性非小细胞肺癌。TSO Comprehensive能对多种预后和预测性生物标志物（如RET）、基因组特征（如肿瘤突变负荷）以及非小细胞肺癌中的新兴生物标志物进行广泛的特征描述和同步检测。 "通过在全球范围内开展的研究，大量证据表明，对晚期癌症患者进行全景变异分析具有临床实用性。"萨拉-坎农研究所（Sarah Cannon Research Institute）早期药物开发部主任、医学博士Vivek Subbiah表示，"因美纳最新推出的用于全景变异分析的体外诊断试剂盒和配套的伴随诊断试剂盒为肿瘤临床专家群体提供了另一种有价值的临床工具，帮助患者采用合适的靶向治疗，从而进一步改善治疗过程和疗效。" TSO Comprehensive将于今年开始向客户发货。根据美国联邦医疗保险和医疗补助服务中心（Centers for Medicare & Medicaid Service）的国家承保范围认定，像TSO Comprehensive这类具有实体瘤伴随诊断报销资质的全景变异分析检测产品可获得报销。通过与制药公司合作，因美纳正在开发更多伴随诊断应用，这些应用将在获得相应的监管批准后添加到TSO Comprehensive检测产品中。这些伴随诊断检测应用将助力突破性的靶向治疗和免疫疗法的推出，改善癌症患者的生活质量。 "我们始终致力于将最领先和高品质的产品与实践引入中国市场，持续推动创新产品在区域市场的应用。"因美纳全球高级副总裁兼大中华区总经理郑磊表示，"随着TSO Comprehensive产品及相关适应症在美国的获批，我们将与中国顶尖的科研、临床机构、药企合作伙伴展开深入探讨与广泛合作，共同为中国市场设计出‘中国方案'。同时，我们也将充分借助中国开放创新的政策优势，在‘先行先试'区域积极探索落地方案，加速相关产品在中国的临床获批和应用，最终造福更多患者。" TSO Comprehensive检测试剂盒的单独CE标志版本已于2022年在欧洲上市。在大中华地区，TruSight Oncology Comprehensive已于2024年5月1日被纳入中国台湾地区的全民健保体系，成为亚洲范围内进入健康保险体系伴随诊断解决方案的"先行者"。欲了解有关TruSight Oncology Comprehensive的更多信息，请点击此处。关于 TruSight Oncology Comprehensive TruSight Oncology Comprehensive是一种定性体外诊断检测产品，它使用因美纳NextSeq™ 550Dx基因测序仪，利用从实体恶性肿瘤患者的福尔马林固定、石蜡包埋（FFPE）肿瘤组织样本中提取的核酸，通过靶向新一代测序技术检测517 个基因的变异。该产品可用于检测DNA中的单核苷酸变异、多核苷酸变异、插入和缺失，以及RNA中24个基因的融合和一个基因的剪接变异。该检测还能报告肿瘤突变负荷（TMB）得分。根据已批准的治疗产品标签，该检测可用作伴随诊断，以确定哪些癌症患者可从表1所列的靶向治疗中获益。此外，该检测还可提供肿瘤分析信息，供有资质的医疗专业人士根据专业肿瘤指南为实体瘤恶性肿瘤患者提供医疗建议。除预期用途说明表1中所列出的基因组结果外，其他基因组结果对任何特定治疗产品的标签使用均不具决定性或规定性。表 1 ：伴随诊断指征肿瘤类型检测到的生物标志物治疗实体瘤 NTRK1/2/3融合 VITRAKVI®（拉罗替尼）非小细胞肺癌 RET融合 RETEVMO®（塞普替尼）前瞻性声明本新闻稿可能包含涉及风险和不确定性的前瞻性声明。我们的业务可能受到以下重要因素的影响，这些因素可能导致实际结果与任何前瞻性声明中的结果存在实质性差异：(i) 我们制造可靠仪器和耗材的能力；(ii) 开发、制造和推出新产品和服务所固有的挑战；(iii) 我们获得或保持政府机构对我们产品的监管批准以及付款人报销的能力；(iv) 我们与其他公司和组织成功合作开发新产品、拓展市场和发展业务的能力，以及我们向美国证券交易委员会提交的文件中详述的其他因素，包括我们最近提交的 10-K 表和 10-Q 表，或在公开电话会议中披露的信息，电话会议的日期和时间已事先公布。我们没有义务，也不打算更新这些前瞻性声明，审查或确认分析师的预期，或提供有关本季度进展的中期报告或更新。关于因美纳因美纳公司致力于推动和激发基因组学的发展而不断改善人类健康。专注创新使我们成为全球基因测序和芯片技术的领导者，并为全球范围的科研、临床和应用市场客户提供专业服务。我们的产品广泛应用于生命科学、肿瘤学、生殖保健、农业及其他新兴领域。欲了解更多信息，请访问www.illumina.com.cn或关注因美纳微信公众号。

诊断试剂上市批准临床研究