Asciminib as Single Agent or in Combination With Nilotinib in the 1st-line Treatment of BCR-ABL1+ Chronic Myeloid Leukemia: a Randomized GIMEMA-GELMC Phase II Study PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML

A phase 2, interventional, randomized unblinded study will be conducted in newly diagnosed CP CML patients, to investigate the efficacy and the safety of asciminib at a dose of 80 mg QD as single agent (arm A) or 40 mg BID in combination with nilotinib 300 mg BID (arm B).
All patients in both arm A and arm B will be treated for a minimum of 2 years (core phase). If they will have achieved a DMR (MR4), or if it will be in the interest of the patient, the treatment will be continued.
During the consolidation phase (2 years) asciminib will be continued at the same dose in both arms; in the combination arm the nilotinib dose will be reduced to 300 mg daily.
The patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment (TFR phase). The rate of TFR at 5 year (1 year after discontinuation) will be evaluated.

开始日期2024-09-01

申办/合作机构

Gruppo Italiano Malattie EMatologiche dell'Adulto

NCT05554341 / Suspended临床2期IIT

Nilotinib and Paclitaxel in Patients With Prior Taxane-Treated Solid Tumors: A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial evaluates nilotinib with paclitaxel for the treatment of patients with solid cancers that are growing, spreading, or getting worse (progressive) and that have previously been treated with taxane therapies. Nilotinib is in a class of medications called kinase inhibitors. It works by binding to and blocking the action of a protein called ABL, which signals tumor cells to multiply. This helps slow or stop the proliferation of tumor cells. Paclitaxel is a drug that blocks cell growth by stopping cell division and it may kill tumor cells. Giving nilotinib with paclitaxel may be effective at treating patients with progressive solid cancers that have previously been treated with taxane therapies.

开始日期2023-07-14

申办/合作机构

National Cancer Institute

NCT05564377 / Recruiting临床2期IIT

Molecular Analysis for Combination Therapy Choice (ComboMATCH)

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.

开始日期2023-04-07

申办/合作机构

National Cancer Institute

100 项与尼洛替尼相关的临床结果

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100 项与尼洛替尼相关的转化医学

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100 项与尼洛替尼相关的专利（医药）

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118

项与尼洛替尼相关的文献（医药）

2023-03-01·International journal of pharmaceutics

Serum and lymph pharmacokinetics of nilotinib delivered by yeast glucan particles per os

Article

作者: Šalamúnová, Petra ; Beránek, Josef ; Lukáč, Peter ; Dammer, Ondřej ; Grus, Tomáš ; Slanař, Ondřej ; Kozlík, Petr ; Kroupová, Jiřina ; Petřík, Jakub ; Ryšánek, Pavel ; Krejčí, Tereza ; Štěpánek, František ; Hubatová-Vacková, Anna ; Šíma, Martin ; Křížek, Tomáš ; Saloň, Ivan

Nilotinib is a selective tyrosine-kinase inhibitor approved for the treatment of chronic myeloid leukemia. It is poorly soluble in aqueous media and has a low oral bioavailability. Nilotinib encapsulation into yeast glucan particles (GPs) was investigated in this work as a means of increasing bioavailability. The amorphization of nilotinib in GPs resulted in an increased dissolution rate, which was confirmed by in vitro experiments using biorelevant dissolution media. Simultaneously, GPs containing nilotinib were effectively taken up by macrophages, which was quantified in vitro on cell cultures. The overall oral bioavailability in a rat model was approximately 39 % for nilotinib delivered in a reference formulation (Tasigna) and was almost doubled when delivered in GPs. The contribution of glucan particles to the lymphatic transport of nilotinib was quantified. When delivered by GPs, cumulative nilotinib absorption via the lymphatic system increased by a factor of 10.8 compared to the reference, but still represented arelative bioavailability of only 1.12 %. The cumulative uptake of GPs in the lymph was found to be 0.54 mg after a single dose of 50 mg. Yeast glucan particles can therefore serve as a drug delivery vehicle with a dual function: dissolution rate enhancement by amorphization, and, to asmaller extent, lymphatic delivery due to macrophage uptake.

2023-03-01·Luminescence : the journal of biological and chemical luminescence

Utility of a xanthene‐based dye for determination of nilotinib using two spectroscopic approaches. Applications to bulk powder, capsules, and spiked human plasma

Article

作者: Nasr, Jenny Jeehan ; Dagher, Diaa ; El‐Enany, Nahed ; Elmansi, Heba

Abstract:

Novel, selective, facile, and precise spectroscopic approaches were validated to determine nilotinib hydrochloride, a tyrosine kinase inhibitor used to treat patients with chronic myeloid leukemia. These approaches depend on the reaction of the tertiary amine group of nilotinib with erythrosine B in the Britton–Robinson buffer at pH 4. Method I, depends on measuring the absorbance of the formed complex at 551 nm. The absorbance concentration plot showed linearity over the concentration range of 1.0 to 9.0 μg/ml. Method II, involved the measurement of the quenching of the native fluorescence of erythrosine B by adding nilotinib in an acidic medium. The fluorescence quenching of erythrosine B was measured at 549 nm after excitation at 528 nm. This approach showed excellent linearity in the concentration range of 0.04 to 0.7 μg/ml. The limit of detection values for Method I and Method II were 0.225 and 0.008 μg/ml, respectively, while the limit of quantitation values for Method I and Method II were 0.68 and 0.026 μg/ml, respectively. To get the optimal conditions, factors that may affect the formation of the ion‐pairing complex were thoroughly examined. The two approaches were carefully validated following the International Conference of Harmonization (ICH Q2R1) guidelines. Statistical assessment of the results achieved using the suggested and previously published comparison approaches showed no significant difference. The approaches were successful in determining nilotinib in a pharmaceutical dosage form as well as spiked human plasma samples. The eco‐friendly properties of the methods were evaluated by three different tools.

2022-10-01·Clinical pharmacology in drug development

Pharmacokinetics, Bioequivalence, and Safety Studies of a Generic Selective Tyrosine Kinase Inhibitor Nilotinib Capsule Versus a Branded Product in Healthy Chinese Volunteers

Article

作者: Huang, Ming ; Wang, Hao ; Lu, Dan ; Zhang, Quanying ; Zhu, Yifang ; Zhou, Wenjia ; Wang, Meng

Abstract:

Nilotinib, a second‐generation tyrosine kinase inhibitor (TKI), has been approved in the United States and Europe as a treatment for patients with newly diagnosed chronic myeloid leukemia (CML)‐chronic phase (CP) and patients with CML‐CP or chronic myeloid leukemia‐accelerated phase (CML‐AP) who are resistant or intolerant to imatinib (a first‐generation TKI). This study compared the bioequivalence and safety of the test nilotinib capsule and reference nilotinib capsule (Tasigna, Novartis) in healthy Chinese volunteers under fasting conditions for marketing authorization in China. The results of the study are reported for the first time. This was a single‐dose, randomized, open‐label, two‐period, and cross‐over study. Thirty healthy volunteers were randomly assigned to receive a single dose of a 200‐mg test or reference capsule under fasting conditions in each period with a 10‐day washout. Plasma samples were analyzed with liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were calculated with WinNonlin software. The geometric mean ratio and the corresponding 90% confidence intervals of Cmax, AUC0‐t, and AUC0‐∞ for nilotinib between the two fixed‐dose combination formulations were within the bioequivalence acceptance range of 80%–125%, therefore the generic and branded formulations were bioequivalent in healthy Chinese volunteers.

105

项与尼洛替尼相关的新闻（医药）

2024-06-27

·药时代

全球唯一！诺华STAMP抑制剂阿思尼布在国内申报上市，用于慢性髓细胞白血病

今日，国家药监局药品审评中心（CDE）官网发布信息显示，诺华（“Novartis”）公司申报的盐酸阿思尼布片的上市申请获受理，拟用于慢性髓细胞白血病（CML）的治疗。阿思尼布（Asciminib）是第一种专门针对ABL肉豆蔻酰口袋（STAMP）的药物，与BCR-ABL1结合的位点与常见TKI不同，有望解决CML后线治疗中TKI耐药和不耐受问题；该药物也是全球唯一获批的STAMP抑制剂。关于阿思尼布阿思尼布是一种变构抑制剂，不是结合ATP位点，而是独特地与BCR-ABL1 的豆蔻酰化口袋结合；该药物对含有T315I抗药突变的肿瘤表现出了纳摩尔级的活性，然而肉豆蔻酰化区及其周围的耐药性突变也成为阿思尼布特有的问题。阿思尼布有望与ATP位点抑制剂联用以实现耐药突变互补，是一个潜在的开发方向。 2021年10月，FDA加速批准asciminib（商品名Scemblix）用于治疗既往接受过两种以上的TKI治疗的Ph+CML-CP成年患者，并完全批准用于治疗携带T315I突变的Ph+ CML-CP成年患者。 2024年1月，公司在新诊断的费城染色体阳性慢性髓性白血病慢性期（Ph+ CML-CP）成年患者的III期ASC4FIRST研究初步分析中取得积极结果；该研究是一项随机、多中心、开放标签的III期临床试验，也是首个且唯一一个与标准治疗CML的一代、二代TKI进行头对头的III期试验；主要终点包括48周时，与研究者选择的二代TKI（尼洛替尼、达沙替尼和博舒替尼）以及伊马替尼相比，每日1次80mg Scemblix治疗组达到MMR的患者比例。结果显示：研究达到双重主要终点，Scemblix第48周的MMR率优于研究者选择的TKIs（伊马替尼、尼洛替尼、达沙替尼和博舒替尼），具有临床意义和统计学意义。同时，Scemblix也表现出良好的安全性和耐受性，不良事件（AE）和治疗中断情况更少，没有观察到新的安全信号。除此以外，Asciminib也是首个在三线后治疗CML时头对头二代TKI取得优效的药物；III期研究ASCEMBL数据显示，asciminib头对头二代TKI在三线后治疗CML时，第96周MMR率分别为37.6%和15.8%，响应率提升超过一倍。在安全性和耐受性方面，asciminib和二代TKI治疗组中导致停药的AE发生率分别为7.7%和26.3%，mDoR分别为23.7个月和7.0个月，并显著改善了患者症状及生活质量。关于STAMP抑制剂据不完全统计，目前在研的STAMP抑制剂有4种。 TGRX-678：是由塔吉瑞独立研发的STAMP抑制剂，目前在中美同时开展临床研究。临床前研究结果表明：（1）TGRX-678 具有高度的靶向特异性和活性，对多种 CML 细胞和携带临床 ATP 位点耐药突变的 Ba/F3 工程细胞系有强抑制作用。（2）TGRX-678 具有良好的动物PK 特性，在动物肿瘤模型中也展现出优异的活性。（3）TGRX-678 和 Ponatinib 联用在 T315M 或 T315I-inclusive 复合突变中的强协同效应，为克服当前临床耐药性挑战提供新的可能。 HS-10382 ：是一款高效、口服STAMP变构抑制剂，于2020 年与美国拓臻生物签署独家产品授权合作协议所引入，目前正在进行I 期临床试验；该药物有望为传统1/2代BCR-ABL TKI进展的T315I耐药突变和多重复合突变患者提供优效治疗，同时与氟马替尼联用提高治疗效果。 AS1266：是亚盛医药自主研发的STAMP变构抑制剂，目前处于临床前的在研阶段。关于CML CML是一种多能干细胞发生恶性转化的克隆性增殖的疾病，导致成熟和未成熟粒细胞的生成显著增多。CML初期常没有症状，疾病进展隐匿并伴有一个非特异性的“良性”阶段（如不适、食欲减退及体重减轻），最终进展到加速期或急变期，并伴有更多的不良表现，如脾大、苍白、瘀斑和出血、发热、淋巴结肿大及皮肤病变。 CML全球的年发病率为（1.6～2）/10万，占成人白血病总数的15%～20%。我国年发病率为（0.39~0.55）/10万。据美国肿瘤协会估计，2022年美国将有超过8800例CML新病例，约1220例死亡。据统计，90％~95％的慢性粒细胞白血病患者存在费城（Ph）染色体。Ph染色体是9号染色体和22号染色体相互易位t（9; 22）产生的一种融合蛋白。在这个易位过程中，9号染色体上的原癌基因ABL片段易位至22号染色体，并与BCR基因融合。嵌合融合基因BCR-ABL 负责产生癌蛋白bcr-abl酪氨酸激酶。bcr-abl癌蛋白具有不受控制的酪氨酸激酶活性，可抑制细胞增殖，减少白血病细胞对骨髓基质的粘附，并保护白血病细胞免于正常的程序性细胞死亡。当前CML的主要治疗药物是Bcr-abl TKI。一代药物甲磺酸伊马替尼于2001年获批上市，开启了CML的靶向治疗时代，显著地改善了CML患者生存期，80%～90%的患者的生存期接近正常人，并提高了患者的生活质量。伊马替尼作为一线治疗初发CML-CP患者长期结果证实，10年生存率为80%～90%。二代TKI（如尼洛替尼、达沙替尼、博舒替尼和拉多替尼）、三代TKI（如普纳替尼）加快和提高了患者的治疗反应率和反应深度，有效克服了大部分伊马替尼耐药，也为伊马替尼不耐受患者提供了更多选择。据统计，伊马替尼销售峰值曾接近50亿美元，Bcr-Abl TKI的市场规模超60亿美元。据悉，Asciminib的单价均约2万美元/盒，折成人民币后年费超过百万元。参考资料 1、各公司官网 2、CDE、华创证券、广发证券封面图来源：pixabay 版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 一年少打300多针！全球首款胰岛素周制剂在华获批国产降糖药创新实录，华领医药的 “海外之声” 中国CXO如何答好「出海」这道题点击这里，发现价值信息！

临床结果临床3期ASCO会议申请上市加速审批

2024-06-25

·GlobeNewswire-Health Care

Shape Therapeutics Appoints Healthcare Industry Leaders David Epstein and Todd Simpson to its Board of Directors

Epstein and Simpson bring significant life sciences industry expertise that will be integral to the Company’s continued growth as a leader in AI for genomic medicineSEATTLE, June 25, 2024 (GLOBE NEWSWIRE) -- Shape Therapeutics, Inc. (ShapeTX), a leader at the convergence of AI and RNA editing to revolutionize genomic medicine, announces the appointments of David Epstein, former CEO of Seagen, and Todd Simpson, former CFO of Seagen, to its board of directors. “We are at a pivotal moment where our investment in breakthrough technologies is now yielding industry-leading results. As we prepare to advance our RNA editing therapies to the clinic, we are thrilled to welcome David and Todd to our board," said Francois Vigneault, Ph.D., chief executive officer of ShapeTX. "Their expertise in scaling life sciences companies, from drug development to clinical success and commercialization, will be invaluable.” David Epstein is a highly respected leader in the pharmaceutical and biotech sectors, renowned for steering Seagen towards a pivotal $44.5 billion acquisition by Pfizer. With over 30 years of global experience in drug development, commercialization, and leadership, David has previously served as an executive partner at Flagship Pioneering and as CEO of Novartis Pharmaceuticals, including its Oncology and Molecular Diagnostic units, transforming it into the second-largest oncology division globally. He has overseen the development and launch of more than 30 new molecular entities, including notable treatments such as Glivec, Tasigna, Gilenya, Afinitor, Cosentyx, Entresto and Padcev. David holds a bachelor's degree in pharmacy from Rutgers University and an MBA from Columbia University. He also serves on the boards of Tempus AI and Valo Health. "Throughout my career, I've been fortunate to be part of companies at the forefront of scientific innovation, witnessing firsthand the profound impact on patients and families." said David Epstein. "Shape has married AI, superior engineering and efficient manufacturing to cure horrific CNS and retinal disease with revolutionary AI RNA-targeted therapy, and I am eager to contribute my experience to accelerate their growth.” Todd Simpson brings more than 40 years of diverse life sciences and industry experience to the ShapeTX board. During his nearly two decades at Seagen, Todd played a crucial role in launching and commercializing four oncology medicines across more than a dozen labeled indications in the United States. He also spearheaded Seagen's international expansion, leading to the commercialization of three medicines in the Americas and Europe. Before Seagen, Todd held several leadership roles, including VP of Finance and Administration, CFO, Treasurer, Secretary at Targeted Genetics Corp. and worked almost ten years in public accounting. He holds a bachelor's degree in accounting and computer science from Oregon State University and has served on the boards of Neoleukin Therapeutics, Aquinox Pharmaceuticals Inc., and Life Science Washington (formerly Washington Biotech and Biomedical Association). "I see remarkable similarities between ShapeTX and the early days of Seagen. It's refreshing and invigorating to work with a team dedicated to long-term, platform-based therapeutic innovation and driven by a mission to help patients in need," said Todd Simpson. About ShapeTX: Shape Therapeutics operates at the convergence of AI and RNA editing to revolutionize genomic medicine. Our proprietary RNA editing technology, RNAfix®, represents a significant leap forward over CRISPR-based tools, achieving 95% editing efficiency in vivo, and a path to one-time curative treatments for thousands of diseases. With over 90 million laboratory-validated guide RNA and 12 billion AAV data points, ShapeTX is building the largest therapeutic RNA foundation model in the industry and becoming the leader in AI for genomic medicine. You can find us at ShapeTX.com and on LinkedIn and X. Media Contact: Lisa Ash TaylorGeneral Counsel and Head of OperationsShape Therapeuticslisa@shapetx.com

高管变更并购

2024-06-21

·生物制品圈

当亚盛迎来命运的杠杆

2024年3月28日，成立15年的Biotech公司亚盛经历过一次股价暴跌，缘由是2023年度业绩公告发布。公告显示2023全年亚盛营业收入2.22亿不及预期，唯一的商业化产品奥雷巴替尼在2023下半年出现明显下滑。而亏损达到9.26亿，期末现金只剩10.38亿，算来只够再烧一年。杨大俊在业绩会上给出的回应说，“除了我杨大俊作为CEO要担心钱的问题，大家都不用担心。” 钱自然要从BD来。一位持仓三年的投资人张博文（化名）在内心里给亚盛的最后期限是9月1日。“如果在第三季度前没有BD，我们就要考虑亚盛的现金流风险。” BD在最后揭晓前都充满悬念。负责BD的首席业务拓展官Jeff Kmetz身在国外，和国内沟通不多。杨大俊提起BD进度的时候，始终在表达要“找到最合适的合作伙伴，争取最好的条件”，让人不禁好奇谁是这个对象是谁。当IR在交流会上透露“竞争对手也想要我们亚盛的产品”时，业内都期待着潜在的合作方是诺华、BMS。最后花落也有“竞品”的武田，属于意料之外、情理之中。张博文直言“我还是蛮欣赏这一次交易的。” 6月14日，在和武田的这场BD交易里，亚盛医药将获得1亿美元首期选择权付款，以及总计12亿美元的后期选择权行使费及分阶段里程碑付款，还有年销售额两位数百分比的销售分成。这款成熟上市产品的BD，十几亿美金的总包，看似不那么亮眼，因为一些临床I期的产品卖价都大于这个数目，但胜在它的首付款是扎扎实实的1亿美金，不像其它一些BD，总额几十亿美金，最终却难以拿到手中。这是一场及时雨——尤其是对这个时期的亚盛。与此同时，亚盛医药还公布，已向美国证券交易委员会保密提交了一份F-1表格登记声明草案，关于建议公司的普通股通过美国存托股份形式进行首次公开发售。在这种场景下，武田和亚盛的合作不只是一个BD这么简单，涉及到奥雷巴替尼的海外权益，武田入股亚盛，以及一家成立15年的18A Biotech公司在美股上市的窗口。三件事情加在一起，在当下中国生物医药寒冬的大环境中，是一家公司挥别过往开启新阶段的转折点。而放在几年前创新药发展的最高光时刻，这场BD很可能淹没在一家家Biotech的高额融资新闻里。 -01- 载入亚盛历史的一天把管线授权给竞争对手是BD策略的一种。一般发生在授权方自知体量小，在市场上难以对抗被授权方时；或者被授权方感受到对方的威胁，认为与其竞争不如收入自己麾下时。沿着这个思路，就不难理解为什么奥雷巴替尼和之前大家猜测的潜在买家诺华无缘。武田的普纳替尼、诺华的阿思尼布和亚盛的奥雷巴替尼同为三代BCR-ABL抑制剂。阿思尼布的开发从2002年启动，最初的临床多为评估与一代抑制剂伊马替尼、二代抑制剂尼洛替尼或达沙替尼联合治疗的效果。当时诺华还没有把阿思尼布当“头牌”。后来诺华才开始重视阿思尼布作为单一药物的价值。2021年，美国FDA批准阿思尼布用于慢性髓系白血病（Ph+CML-CP）的三线治疗。阿思尼布2023年销售额达4亿美元，入选2023年20大畅销新药。今年6月1日，一项关于阿思尼布用于慢性髓系白血病一线治疗的三期临床达双主要终点，放量在即。从诺华的角度，阿思尼布已经“足够好了”，不需要再引进一个类似的管线。但武田的普纳替尼存在心脑血管不良事件等安全短板，而且专利在2026-2027年到期。奥雷巴替尼正好可以顶替普纳替尼的位置，接过武田在普纳替尼上投入的团队和资源。不过，这是一项对竞品发起的授权引进，是美国联邦贸易委员会(Federal Trade Commission,“FTC”)重点审查的领域。FTC对反垄断审查趋严，主要关注的通过收购竞品压价,限制竞对公司发展的行为。这也是为什么亚盛和武田签署的是独家选择权协议。独家选择权通常不直接限制竞争或导致市场垄断，加上有明确的时间限制，对市场竞争的长期影响较小，因此更容易通过反垄断审查。除了独家选择权协议本身，武田对亚盛进行了股权投资。武田出资7500万美元获得亚盛7.73%的股份成为公司二股东。首付款加股权投资，共1.75亿美元，足够为亚盛在一段时期内解除现金流压力。亚盛也没闲着，恰好在这段时间申请在美股上市，抓住了可能是近几年唯一可以高发的时机。三件事在同一天发声，对于亚盛自身来说，也是超预期的。但从种种细节来看，这次deal是深思熟虑的结果。 -02- 慢热型biotech 做亚盛的投资人很考验心态。亚盛进行BD交易的时机一向比较靠后。亚盛与武田的deal发生在进入全球三期注册性临床之后。在与信达达成奥雷巴替尼国内权益的交易时，亚盛已经提交奥雷巴替尼的上市申请。亚盛不仅拿到授权交易款，双方按照50%:50%对来自共同推广部分的利润进行分成。信达也入股亚盛，双方形成长期利益绑定关系。在下一个重磅管线Bcl-2选择性抑制剂APG-2575的临床开发中，亚盛已经和阿斯利康搭上线。双方关于APG-2575与阿可替尼的联合治疗的临床合作从二期延续到三期，中间是有谈BD时机的，但至今没有推进BD。对于亚盛BD，外界看起来“慢悠悠”的思路，杨大俊的回应是：“我们也会通过各种路径找最合适的伙伴合作伙伴，最好的条件，同时也要考虑整体的平衡各种因素。”管线自然是越到临床后期越有价值，特别是与MNC交易中，一期临床项目的授权首付款大概2000万美元，二期最多5000-6000万，进入三期才能上亿。去年下半年，奥雷巴替尼在国内的销量出现下滑，放量比较慢。因为CML特别是携T315I突变的CML国内发病率低，奥雷巴替尼真正有竞争力的适应症PH+ALL还没获批，而且医疗反腐因素扰动，超适应症使用受限。 “我们其实对于奥雷巴替尼国内销售放量的速度没有很高的预期，正常推进慢慢卖就可以了。”做为投资人的张博文真正关注的是奥雷巴替尼海外表现，以及下一个重磅管线Bcl-2选择性抑制剂APG-2575。 2022年3月15日，APG-2575治疗复发/难治性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(R/R CLL/SLL)的中国关键注册II期临床试验(APG2575CC201)已完成首例患者给药。当时预计2023年上半年实现全部患者入组。后来对外口径变成2023年内完成国内关键注册临床研究入组，预计在2024年内在中国递交新药上市申请。关注亚盛和持仓亚盛的投资人对其临床进展都有很多顾虑。"我觉得有时候也是投资人太着急。做药和证券市场短线投资不同，一款新药10年能搞成都是很好的结果，有时候隔一两年曾经被否定的药又被拿出来做成功了，不是所有人都能忍耐做药的节奏。"张博文补充说，“并没有出现亚盛在临床试验中遇到阻碍的讯息，所以我们推测钱肯定是一部分因素，要花钱的地方有很多，公司能省则省。第二，公司可能在与监管机构的沟通上花了很多的时间。第三亚盛不能失败，可能因此特别谨慎。” 人人都想走百济神州高举高打的路线。但在海外市场没打开局面之前，谨小慎微的Biotech占大多数。接下来，亚盛两大核心品种，奥雷巴替尼及APG-2575的多项全球注册III期临床试验等待推进。根据雪球博主雨霖冰整理，奥雷巴替尼治疗一线ph+ ALL的全球三期临床已经于2023年9月2日启动，全球入组人数350人（国内200+海外150），主要完工时间是2024月12月31日。奥雷巴替尼治疗三线CML及T35I突变的全球三期临床于2024年5月启动，主要完工时间是2025年12月。 APG-2575治疗二线CLL的全球三期临床于2024年1月开始入组，由APG-2575+BTK对照BTK，临床主要终点是12个月PFS。APG-2575治疗1.5线CLL的全球注册临床，获CDE批准治疗一线CLL的大三期临床也开始招募病人。在资金紧迫感得以缓解的情况下，考验亚盛海外临床推进能力和效率的时候到了。 -03- 美股上市，打开亚盛的想象空间三连公告后，6月17日，亚盛医药港股早盘股价最高触及29.80港元/股，涨幅高达29.28%。股价没有冲破天花板。 "此前，公募机构和大的私募机构还没有把亚盛纳入标的。亚盛市值70多亿，每天交易量2000-3000万，资金容量太小。” 在美股上市或许是会成为一个加速力。港股市场和美股市场的资金有较高的互动性，投资者可以根据两地市场的表现轻易地调配资金，这使得两地股市的涨跌较易同步。而且两地经济环境本身就存在较高的相关性，美国经济走强或走弱时，香港的经济和企业表现也会相应受到影响，这亦会加强股市之间的相关性。两个池子里的水互相流动，肯定会有一个差距收敛的过程，美股的定价会影响到港股股价。比如说如果亚盛以20亿美元的市值上市，港股第二天就会涨一倍。港股如今面临两大问题，外资机构资金撤离，流动性差。计划在美股上市的创新药企不止亚盛一家。但想要在美股IPO，虽然美股上市不强制要求基石投资者，但公司也会和大型机构接触，争取它们认购一定份额的股份——不管资本运作有多眼花缭乱，最终又回到管线的价值这一核心问题。而机构投资者众的美股市场，大机构资金入场与否，又会成为其它类型投资者的一个风向标。现在理解杨大俊的投资人声音多了一些。“亚盛不太喜欢跟投资者沟通，也有好处，与其每天跟搞投资者关系，不如多花点时间跟阿斯利康、武田多聊一聊，这是我们作为投资人来说更愿意见到的事情。短期内不做市值管理也可以理解，如果亚盛已经达到200亿市值，我相信他们也会拿出更多的时间来做这个事。” 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

引进/卖出财报临床1期

100 项与尼洛替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06413	尼洛替尼	L01XE08	DB04868

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
加速期慢性骨髄性白血病	美国	Novartis Pharmaceuticals Corp.	2010-06-17
费城染色体阳性白血病	欧盟	Novartis Europharm Ltd.	2007-11-19
费城染色体阳性白血病	冰岛	Novartis Europharm Ltd.	2007-11-19
费城染色体阳性白血病	列支敦士登	Novartis Europharm Ltd.	2007-11-19
费城染色体阳性白血病	挪威	Novartis Europharm Ltd.	2007-11-19
费城染色体阳性慢性粒细胞白血病	瑞士	Novartis Pharma Schweiz AG	2007-07-24

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
慢性期慢性髓性白血病	临床3期	阿根廷	Novartis Pharmaceuticals Corp.	2009-06-01
慢性期慢性髓性白血病	临床3期	澳大利亚	Novartis Pharmaceuticals Corp.	2009-06-01
慢性期慢性髓性白血病	临床3期	巴西	Novartis Pharmaceuticals Corp.	2009-06-01
慢性期慢性髓性白血病	临床3期	加拿大	Novartis Pharmaceuticals Corp.	2009-06-01
慢性期慢性髓性白血病	临床3期	法国	Novartis Pharmaceuticals Corp.	2009-06-01
慢性期慢性髓性白血病	临床3期	西班牙	Novartis Pharmaceuticals Corp.	2009-06-01
转移性胃肠道间质瘤	临床3期	中国	Novartis Pharmaceuticals Corp.	2009-06-01
转移性胃肠道间质瘤	临床3期	阿根廷	Novartis Pharmaceuticals Corp.	2009-06-01
转移性胃肠道间质瘤	临床3期	巴西	Novartis Pharmaceuticals Corp.	2009-06-01
转移性胃肠道间质瘤	临床3期	加拿大	Novartis Pharmaceuticals Corp.	2009-06-01

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临床结果

适应症

分期

评价

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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


NCT02611492 (GRAAPH-2014, Pubmed)	临床3期	费城染色体阳性急性淋巴细胞白血病巩固	156	Nilotinib + Cytarabine	鹽築遞繭鑰鑰鏇淵繭糧(願淵選襯壓鑰襯網艱壓) = 餘築夢夢餘顧製艱襯築餘蓋遞積願鑰積醖糧築 (鹽繭憲鏇餘膚獵蓋壓鬱 ) 更多	不佳	2024-03-07
NCT02611492 (GRAAPH-2014, Pubmed)	临床3期	费城染色体阳性急性淋巴细胞白血病巩固	156	Nilotinib	鹽築遞繭鑰鑰鏇淵繭糧(願淵選襯壓鑰襯網艱壓) = 鬱窪夢齋遞網醖衊鹽獵餘蓋遞積願鑰積醖糧築 (鹽繭憲鏇餘膚獵蓋壓鬱 ) 更多	不佳	2024-03-07
NCT01735955 (CTgov)	临床4期	转移性胃肠道间质瘤 \| 急性淋巴细胞白血病 \| 费城染色体阳性慢性粒细胞白血病	57	Nilotinib	夢簾願醖艱鏇願鬱蓋觸(顧蓋鏇積積積顧網築鏇) = 窪廠廠鹽築淵蓋範範網齋壓衊構膚艱鬱範觸蓋 (鹽鑰遞窪膚窪製糧鹽醖, 選鬱遞獵顧壓鹹齋鏇蓋 ~ 鏇膚積憲餘鏇鬱範窪遞) 更多	-	2024-02-08
NCT02546674 (CTgov)	临床4期	慢性期慢性髓性白血病	171	Nilotinib	夢窪鑰遞鏇蓋觸築鑰鏇(獵夢鹹製鏇範選築繭獵) = 繭醖簾繭糧鹽鬱窪遞範製遞獵獵獵廠築構鏇製 (觸艱蓋簾遞鏇窪餘簾製, 壓製構糧憲遞糧選網積 ~ 齋蓋蓋選製網繭窪鬱襯) 更多	-	2022-07-22
NCT04006847 (CTgov)	临床1/2期	慢性期慢性髓性白血病	1	Eicosapentaenoic Acid	範鑰膚廠製觸選遞醖鏇(糧選築簾夢餘繭壓獵糧) = 網鏇餘積鬱鹽製遞齋構簾壓糧淵齋夢鑰醖艱選 (糧壓艱觸觸顧餘積顧艱, 鑰鬱壓構遞膚顧繭製膚 ~ 鹹齋願顧獵衊網淵淵鑰) 更多	-	2022-07-01
NCT02379416 (ASCO2022) 人工标引	临床1期	难治恶性实体肿瘤	44	Nilotinib+paclitaxel	餘憲鬱夢製築窪廠蓋觸(製艱觸顧衊遞構艱蓋構) = 300 mg oral nilotinib twice daily and 80 mg/m2 intravenous paclitaxel on days (D) 1, 8, and 15 of each 28-day cycle 襯醖網遞願製網衊顧觸 (鏇壓鹽鏇淵衊窪廠築艱 ) 更多	积极	2022-06-02
NCT02353728 (CTgov)	临床2期	慢性期慢性髓性白血病 \| 白血病浸润	16	Nilotinib	淵鏇窪淵鹽鏇衊壓簾齋(襯鏇醖繭鏇獵衊膚淵積) = 淵襯獵壓簾鏇窪選鬱築鑰獵醖膚鹹願膚壓醖鹽 (顧網齋觸餘蓋糧鹹鹽醖, 齋窪蓋壓範夢繭製遞齋 ~ 衊憲夢獵夢鬱鏇蓋窪鏇) 更多	-	2022-03-25
NCT01743989 (Enestpath, ASH2021) 人工标引	临床3期	费城染色体阳性慢性粒细胞白血病	619	Nilotinib Hydrochloride (Arm 1 )	鬱鹽廠積襯鏇鹽膚構糧(獵積顧繭構築願範鬱鏇) = 鬱構製餘艱襯繭顧鹹鹽觸繭繭餘鬱蓋淵艱鹽艱 (鬱糧選餘蓋鏇糧鑰鹽窪, 23.7 ~ 41.1) 更多	-	2021-11-05
NCT01743989 (Enestpath, ASH2021) 人工标引	临床3期	费城染色体阳性慢性粒细胞白血病	619	Nilotinib Hydrochloride (Arm 2 )	鬱鹽廠積襯鏇鹽膚構糧(獵積顧繭構築願範鬱鏇) = 獵遞襯顧觸範築鏇顧製觸繭繭餘鬱蓋淵艱鹽艱 (鬱糧選餘蓋鏇糧鑰鹽窪, 28.2 ~ 47.5) 更多	-	2021-11-05
NCT02611492 \| EUCTR2014-002146-44-BE (Graaph-2014, ASH2021) 人工标引	临床3期	费城染色体阳性急性淋巴细胞白血病 Philadelphia Chromosome Positive	156	chemotherapy+Nilotinib Hydrochloride (arm B + MTX 1 g/sqm over 24h only)	製構窪夢鏇選鑰遞製鹹(廠獵遞築範範憲願醖淵) = 廠壓鑰衊餘夢鑰淵窪鏇積鑰顧夢鹽網選選簾鏇 (憲襯積網鏇衊醖蓋鹹簾 ) 更多	非劣	2021-11-05
	临床3期	费城染色体阳性急性淋巴细胞白血病 Philadelphia Chromosome Positive	156	chemotherapy+Nilotinib Hydrochloride (arm A + MTX 1 g/sqm over 24h, HD-AraC 3 g/sqm/12h for 2 days)	製構窪夢鏇選鑰遞製鹹(廠獵遞築範範憲願醖淵) = 範鹹糧遞觸鹽範憲齋夢積鑰顧夢鹽網選選簾鏇 (憲襯積網鏇衊醖蓋鹹簾 ) 更多	非劣	2021-11-05
NCT00644878 (CTgov)	临床2期	慢性期慢性髓性白血病 \| 费城染色体阳性白血病	18	Nilotinib	醖糧醖憲積憲鬱鑰鬱糧(構鹽壓壓壓遞遞憲範壓) = 繭範淵鑰壓繭鏇選夢蓋廠獵選糧衊獵夢獵鑰選 (衊積壓積醖襯鑰窪範繭, 醖願餘鬱鬱願鏇繭顧構 ~ 蓋膚齋獵鑰膚範淵鏇糧) 更多	-	2021-08-18
NCT01743989 (Enestpath, CTgov)	临床3期	慢性期慢性髓性白血病	620	Nilotinib (Nilotinib 24-month Treatment)	築獵構糧遞夢網範鑰構(範夢構夢壓醖構窪膚鬱) = 膚繭繭築襯壓鬱糧繭遞鬱窪窪顧鑰窪簾淵淵鹽 (夢範襯艱醖鑰壓鏇鑰膚, 遞蓋獵簾蓋顧醖壓襯糧 ~ 鑰鹹繭淵鏇艱製構繭構) 更多	-	2021-07-15
NCT01743989 (Enestpath, CTgov)	临床3期	慢性期慢性髓性白血病	620	Nilotinib (Nilotinib 36-month Treatment)	築獵構糧遞夢網範鑰構(範夢構夢壓醖構窪膚鬱) = 醖獵築繭鹽夢憲鏇窪廠鬱窪窪顧鑰窪簾淵淵鹽 (夢範襯艱醖鑰壓鏇鑰膚, 憲鹽鹽積夢衊繭壓遞簾 ~ 齋膚簾壓願糧鏇壓選鏇) 更多	-	2021-07-15