A Double-blind, Oral, Multiple-dose, Parallel, Randomized Study to Evaluate Efficacy and Safety of Endoxifen in Bipolar I Disorder Patients with Acute Mania Episodes with or Without Mixed Features

Bipolar disorder (BPD) is a chronic debilitating illness characterized by drastic swings in mood, energy and functional ability that affects the adult population. Endoxifen is an active metabolite of the marketed drug Tamoxifen and the present study aims to evaluate the efficacy and safety of 8 mg endoxifen in the Bipolar I disorder patient population compared to a placebo arm. Endoxifen will be compared to a placebo to demonstrate that the test product is active and to establish that the study is sufficiently sensitive to detect differences between the investigational products. Thus, Endoxifen will be compared to placebo to demonstrate that the test product is safe and active.

开始日期2024-03-19

申办/合作机构

Jina Pharmaceuticals, Inc.

[+1]

NCT06075953 / Recruiting临床2期

DCIS: RECAST Trial -Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: a Breast Cancer Prevention Pilot Study

The goal of this trial is to see if active surveillance monitoring and hormonal therapy in patients diagnosed with ductal cell carcinoma in situ (DCIS), an early stage of breast cancer, can be an effective management of the disease.
Participants will be asked to receive control hormonal therapy or an investigational hormonal therapy treatment. Participants will be asked to return for evaluation with MRI at three months and six months. Depending on the evaluation participants will have the option to continue on the treatment. If the evaluation suggests surgery is recommended, the participant will discontinue the study treatment and will undergo surgery. In addition to the treatment and MRI evaluation, participants will be asked to provide blood sample to understand their immune status, provide saliva sample for genetic testing, provide the study with a portion of the tissue or slides generated from tissue removed during surgery performed as part of their standard of care.

开始日期2024-02-14

申办/合作机构

Quantumleap Healthcare Collaborative

NCT05607004 / Recruiting临床2期

A Randomized Phase 2 Non-inferiority Trial of (Z)-Endoxifen and Exemestane + Goserelin as Neoadjuvant Treatment in Premenopausal Women With ER+/HER2- Breast Cancer

This open-label research study is studying (Z)-endoxifen as a possible treatment for pre-menopausal (still having periods) women with ER+/HER2- breast cancer. (Z)-endoxifen is a selective estrogen receptor modulator or "SERM." SERMs work to treat cancer by blocking the body's natural estrogen from binding to cancer cells. This study includes a pharmacokinetic part (PK, how the drug works in your body) and a treatment part. The primary purpose of the study is to see how (Z)-endoxifen works on tumor cell growth by monitoring a cancer marker called Ki-67. Ki-67 will be measured by biopsy of the breast after about 4 weeks of treatment. If your cancer is responding to treatment based on the Ki-67 results, you may continue treatment up to 24 weeks or until surgery.
The PK part of the study will be enrolled first, enrolling about 18 study participants who will all receive oral once daily (Z)-endoxifen treatment. 12 of these participants will be randomly assigned to treatment with an equal (50/50) chance to be assigned to (Z)-endoxifen or (Z)-endoxifen + goserelin (a medication given to block the ovaries from making estrogen and is also called ovarian suppression). This part of the study will help select the dose of (Z)-endoxifen to use in the treatment part by measuring the levels of (Z)-endoxifen in the blood stream and determine how long it takes for the body to remove it.
About 160 study participants will be enrolled in the treatment part. The treatment part will help to determine how oral once daily (Z)-endoxifen, when taken by itself, compares to oral once daily exemestane (a medication that decreases the amount of estrogen in the body, also known as an aromatase inhibitor) and monthly injections of goserelin. Exemestane and goserelin taken together is a standard treatment regimen for premenopausal patients with ER+/HER2- breast cancer. Study participants are randomly assigned to treatment with an equal (50/50) chance to be assigned to (Z)-endoxifen or standard treatment.
Study participation is up to 24 weeks of treatment followed by surgery.

开始日期2023-02-14

申办/合作机构

Atossa Therapeutics, Inc.

[+1]

100 项与内昔芬相关的临床结果

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100 项与内昔芬相关的专利（医药）

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项与内昔芬相关的文献（医药）

2024-09-21·Indian Journal of Psychological Medicine

The Antimanic Effect of Endoxifen in Patients with Bipolar Disorder with Renal Comorbidities: Case Series.

Article

作者: Kuraria, Astut ; Vishwanath, Rashmi ; Nagaraj, Anil Kumar M ; Kamath, Avinash ; Soman, Savitha

The conventional and standard pharmacological approaches in the management of bipolar disorders include mood stabilizers and second-generation antipsychotics. However, renal problems owing to the gold standard mood stabilizer, lithium, is three times that of the general population. As bipolar I disorder (BPD I) is associated with overactive protein kinase C (PKC) intracellular signaling, a novel approach in the management of acute mania/mixed affective states of bipolar disorder includes the use of PKC inhibitors, such as Tamoxifen and its derivative metabolite molecule, Endoxifen. Our objective is to report two cases of bipolar disorder that presented in acute manic episodes, with preexisting renal disease, and safe use of Endoxifen as an adjunct/monotherapy for rapid control of symptoms. According to our study, Endoxifen can be used as an anti-manic agent, either as monotherapy or as an adjunct, in patients with renal disease. It can also be used as an effective cover therapy for bipolar disorder patients requiring steroids for the treatment of renal pathology, though long-term studies are needed to assess the long-term safety and efficacy.

2024-09-01·Clinical pharmacology and therapeutics

Nonlinear Mixed‐Effects Model of Z‐Endoxifen Concentrations in Tamoxifen‐Treated Patients from the CEPAM Cohort

Article

作者: Swen, Jesse J ; Guchelaar, Henk-Jan ; Mikus, Gerd ; Mathijssen, Ron H J ; Hertz, Daniel L ; Michelet, Robin ; Mc Laughlin, Anna M ; Helland, Thomas ; van Schaik, Ron H N ; Kloft, Charlotte ; Dalenc, Florence ; Thomas, Fabienne ; Søiland, Håvard ; White-Koning, Melanie ; Klima, Fenja ; Schwab, Matthias ; Neven, Patrick ; Mellgren, Gunnar ; Brauch, Hiltrud ; Mürdter, Thomas ; Koolen, Stijn L W ; Schroth, Werner

Tamoxifen is widely used in patients with hormone receptor‐positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z‐endoxifen. The Z‐endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z‐endoxifen concentration thresholds are considered infeasible. Therefore, we aim to validate the association between Z‐endoxifen concentration and tamoxifen treatment outcomes, and identify a Z‐endoxifen concentration threshold of tamoxifen efficacy, using pharmacometric modeling and simulation. As a first step, the CYP2D6 Endoxifen Percentage Activity Model (CEPAM) cohort was created by pooling data from 28 clinical studies (> 7,000 patients) with measured endoxifen plasma concentrations. After cleaning, data from 6,083 patients were used to develop a nonlinear mixed‐effect (NLME) model for tamoxifen and Z‐endoxifen pharmacokinetics that includes a conversion factor to allow inclusion of studies that measured total endoxifen but not Z‐endoxifen. The final parent‐metabolite NLME model confirmed the primary role of CYP2D6, and contributions from body weight, CYP2C9 phenotype, and co‐medication with CYP2D6 inhibitors, on Z‐endoxifen pharmacokinetics. Future work will use the model to simulate Z‐endoxifen concentrations in patients receiving single agent tamoxifen treatment within large prospective clinical trials with long‐term survival to identify the Z‐endoxifen concentration threshold below which tamoxifen is less efficacious. Identification of this concentration threshold would allow personalized tamoxifen treatment to improve outcomes in patients with hormone receptor‐positive breast cancer.

2024-07-01·Clinical pharmacology and therapeutics

A Genome‐Wide Association Study of Endoxifen Serum Concentrations and Adjuvant Tamoxifen Efficacy in Early‐Stage Breast Cancer Patients

Article

作者: Dezentjé, Vincent Olaf ; Sanchez‐Spitman, Anabel Beatriz ; Böhringer, Stefan ; Guchelaar, Henk‐Jan ; Gelderblom, Hans ; Swen, Jesse Joachim

Tamoxifen is part of the standard of care of endocrine therapy for adjuvant treatment of breast cancer. However, survival outcomes with tamoxifen are highly variable. The concentration of endoxifen, the 30–100 times more potent metabolite of tamoxifen and bioactivated by the CYP2D6 enzyme, has been described as the most relevant metabolite of tamoxifen metabolism. A genome‐wide association study (GWAS) was performed with the objective to identify genetic polymorphisms associated with endoxifen serum concentration levels and clinical outcome in early‐stage breast cancer patients receiving tamoxifen. A GWAS was conducted in 608 women of the CYPTAM study (NTR1509/PMID: 30120701). Germline DNA and clinical and survival characteristics were readily available. Genotyping was performed on Infinium Global Screening Array (686,082 markers) and single nucleotide polymorphism (SNP) imputation by using 1000 Genomes. Relapse‐free survival during tamoxifen (RFSt) was defined the primary clinical outcome. Endoxifen serum concentration was analyzed as a continuous variable. Several genetic variants reached genome‐wide significance (P value: ≤5 × 10−8). Endoxifen concentrations analysis identified 430 variants, located in TCF20 and WBP2NL genes (chromosome 22), which are in strong linkage disequilibrium with CYP2D6 variants. In the RFSt analysis, several SNP were identified (LPP gene: rs77693286, HR 18.3, 95% CI: 15.2–21.1; rs6790761, OR 18.2, 95% CI: 15.5–21.1). Endoxifen concentrations have a strong association with the chromosome 22, which contains the CYP2D6 gene.

项与内昔芬相关的新闻（医药）

2024-04-30

·PRNewswire

As Early-Onset Breast Cancer Cases Soar in North America and EU, Biotech Ramps Up Response

USA News Group Commentary VANCOUVER, BC, April 30, 2024 /PRNewswire/ -- USA News Group – An alarming rise in early-onset cancers has medical experts very concerned, as cancer cases in younger people are rising sharply. In particular, a surge in cases of breast cancer is being witnessed in Canada, the USA, and the EU, with extra concern to patients thought to be in remission contracting breast cancer a second time, according to a new study from the University of Cambridge. However, there's still optimism towards new treatments, and significant growth of 9.3% CAGR in the metastatic HR+/HER2- breast cancer market through 2032 has treatment developers working harder to make gains for patients. Among the biotech companies currently making strides are O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), IceCure Medical Ltd (NASDAQ: ICCM), Atossa Therapeutics, Inc. (NASDAQ: ATOS), Arvinas, Inc. (NASDAQ: ARVN), and Pfizer Inc. (NYSE: PFE) (NEO: PFE). Following a Fast Track Designation by the FDA in late 2022 for Oncolytics Biotech Inc.'s (NASDAQ: ONCY) (TSX: ONC) drug candidate, pelareorep, for pancreatic cancer treatment, the company is now gaining traction towards another pivotal FDA engagement, this time focusing on breast cancer. Recently, Oncolytics announced that they had submitted a Type C meeting request to the FDA to discuss a forthcoming trial for pelareorep aimed at treating HR+/HER2- metastatic breast cancer (mBC) patients. "A key focus for Oncolytics in 2024 is defining the regulatory path for pelareorep in breast cancer treatment," said Matt Coffey, President and CEO of Oncolytics. "We are optimistic that pelareorep, in combination with paclitaxel, could significantly enhance clinical outcomes for patients with HR+/HER2- metastatic breast cancer. Our position is strengthened by encouraging data from two randomized studies (BRACELET-1 and IND-213) and the AWARE-1 study, paving the way for the next phase of pelareorep's development and registration." Dr. Coffey has shared that Oncolytics' continuous interactions with clinical collaborators and partners have been instrumental in crafting a detailed and persuasive briefing document. The company looks forward to meeting with the FDA in Q2 2024 to finalize the trial design and goals for using pelareorep in treating metastatic breast cancer. This meeting is crucial for advancing this promising therapy toward patient use. With expected survival data from its BRACELET-1 study and constructive dialogues with the FDA, Oncolytics is optimistic that 2024 will be a landmark year for the company and its stakeholders. "The data from the randomized BRACELET-1 trial showcased compelling results for the pelareorep/paclitaxel combination therapy in HR+/HER2- metastatic breast cancer patients, with a nearly tripled confirmed response rate, a 50% improvement in median progression-free survival, and a hazard ratio of 0.29 compared to the paclitaxel alone control," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics. "Importantly, these data support the statistically significant near doubling of median overall survival in another randomized phase 2 study, IND-213, which also evaluated pelareorep and paclitaxel in HR+/HER2- metastatic breast cancer patients." Also seeking the FDA's attention, Israel-based IceCure Medical Ltd (NASDAQ: ICCM) recently reported its final ICE3 breast cancer cryoablation trial results with 100% patient and physician satisfaction and 96.3% recurrence-free rate for its ProSense® System, a minimally-invasive cryoablation technology that destroys tumors by freezing as an alternative to surgical tumor removal. With this new data in hand, IceCure has submitted final data to the FDA, requesting marketing authorization for ProSense® for the indication of treating patients with early-stage T1 invasive breast cancer with cryoablation and adjuvant hormone therapy. ProSense® has already received FDA Breakthrough Designation and is cleared for use in the US for several other indications, including treating benign tumors of the breast, and tumors in the kidney and liver. "We believe ICE3 is a ground-breaking study and are excited to report that the efficacy data of our minimally invasive ProSense® cryoablation procedure show similar outcomes in recurrence compared to more invasive breast surgery, the current standard of care for early-stage breast cancer," said Eyal Shamir, CEO of IceCure. "Initial reimbursement codes are already in place and our U.S. marketing and commercial team is ready, as we await the FDA's response. Driven by favorable healthcare economics combined with patient satisfaction and demand, we expect rapid adoption pending FDA granting the DeNovo Classification Request for Marketing Approval." A new clinical trial was announced by Atossa Therapeutics, Inc. (NASDAQ: ATOS) to evaluate the company's proprietary (Z)-endoxifen in combination with abemaciclib (VERZENIO®), a cyclin-dependent kinase (CDK) 4/6 inhibitor marketed by Eli Lilly and Company, in women with ER+/HER2- breast cancer. Set to enroll approximately 20 newly diagnosed women, the new study arm will have participants receiving 40mg (Z)-endoxifen once daily in combination with 150mg abemaciclib twice daily for a total of 24 weeks prior to surgery. "Endocrine therapy in combination with CDK 4/6 inhibition is a widely used treatment for patients with advanced-stage ER+ breast cancer and as an adjuvant therapy for node positive, hormone positive early-stage disease, found at the time of surgical resection," said Dr. Laura Esserman, director of the University of California San Francisco Breast Care Center and founder of Quantum Leap Healthcare Collaborative. "Women with high clinical stage but less proliferative tumors (molecularly low risk or those with late recurrence risk) are challenging to treat. Late recurrence is high regardless of either endocrine or chemotherapy. Thus, we are looking for new combined treatments, which can be used in the pre-surgery (neoadjuvant) setting. We look forward to learning more about the potential of (Z)-endoxifen in combination with abemaciclib in the neoadjuvant setting in the I-SPY TRIAL." Vepdegestrant (ARV-471) is another treatment that recently received FDA Fast Track Designation, which is a novel oral PROteolysis Targeting Chimera (PROTAC®) ER degrader that is being jointly developed by Arvinas, Inc. (NASDAQ: ARVN), and Pfizer Inc. (NYSE: PFE) (NEO: PFE). The ongoing Phase 3 VERITAC-2 clinical trial is evaluating vepdegestrant or fulvestrant in patients with locally advanced or metastatic ER+/HER2- breast cancer who have been previously treated with an endocrine-based therapy. "The receipt of Fast Track designation reinforces the potential of vepdegestrant to provide an important new therapeutic option for people with ER+/HER2- breast cancer whose disease has progressed," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "We are proud to continue our legacy of developing innovative treatment options for people impacted by metastatic breast cancer and look forward to working with the FDA as we advance our development program for vepdegestrant." Article Source: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCE USA News Group

快速通道临床2期临床结果突破性疗法

2024-01-26

·Pharmaceutical Technology

Atossa Therapeutics progresses Phase II preventative breast cancer therapy

Atossa Therapeutics’ CEO discussed updates for its breast cancer program. Credit: NDAB Creativity via Shutterstock Atossa Therapeutics estimates a Q3 readout of a Phase II trial that studies the company’s lead asset z-endoxifen, says CEO Dr. Steven Quay, in an interview with Pharmaceutical Technology . In December, the US-based biotech announced that it had completed enrollment for its Karisma endoxifen Phase II trial (NCT05068388), reaching 80% of its initial goal. Atossa is conducting the study at the South General Hospital in Stockholm, recruiting 240 pre-menopausal women with measurable MBD. Quay said that the company estimates a Phase II data readout for the trial in Q3 2024. The Karisma study is investigatings Z-endoxifen as a preventative treatment for breast cancer. Quay mentions that the US Food and Drug Administration (FDA) typically does not approve preventative therapies for cancer as many patients pass away during the trial. Furthermore, he highlights the uncertainty surrounding the ideal trial length for preventative studies and choosing the necessary endpoints. The company plans to discuss Phase III plans with the FDA to devise an appropriate trial design. Atossa is also investigating the drug in the I-Spy 2 trial (NCT01042379) and the EVANGELINE trial (NCT05607004) for the treatment of ER+ invasive breast cancer in pre-and postmenopausal women and grade 1 or 2 ER+/HER2 breast cancer in premenopausal women respectively. Z-endoxifen acts by binding to oestrogen receptors, causing a blockage of the oestrogen-dependent gene. The therapy has a patented oral enteric capsule formulation that stabilises it upon oral administration. In 2024, the company plans to present data from its ongoing trials at multiple conferences, says Quay. This includes the American Association for Cancer Research (AACR) annual meeting in April, and the American Society of Clinical Oncology (ASCO) annual meeting in June, says Quay. In a 9 January letter to investors, Quay declared that the company had “a strong balance sheet with no debt and cash, cash equivalents and restricted cash of $94 million as of September 30, 2023.” The company achieved this through the June 2023 launch of a share repurchase program, which allowed them to raise $1.475 million in 2023, amongst other things. The company has extended this share repurchase program through to 31 December 2024. The program permits the purchase of up to $10 million of Atossa’s common stock, including purchases made in 2023. Quay says the company is also open to partnerships to potentially test its drug in a combination therapy setting . He says that once Phase II data has released, the company may leverage it to begin partnership discussions.

临床2期ASCO会议

2024-01-18

·CPHI制药在线

FDA批准的癌症新药Nirogacestat，NCCN指南1类推荐

关注并星标CPHI制药在线美国国家综合癌症网络（National Comprehensive Cancer Network，NCCN）日前公布的最新版相关指南显示，基于FDA日前的批准，作为硬纤维瘤患者全身治疗选择的γ分泌酶抑制剂Nirogacestat（Ogsiveo），被授予首选的1类推荐。 Nirogacestat被纳入美国重磅NCCN指南并且1类推荐，成为本药的又一重要里程碑，为临床用药增添新证。NCCN软组织肉瘤指南（2023-12月发布）图片来源：NCCN官网 1.1 Nirogacestat简介 Nirogacestat于2023年11月27日首次美国获批上市，FDA 此前授予该药用于治疗硬纤维瘤的突破性疗法、快速通道和孤儿药资格。根据FDA新闻稿，该药是首个被批准用于治疗硬纤维瘤患者的药物。Nirogacestat结构（二氢溴酸盐）图片来源：FDA批准说明书【公司】Spring Works Therapeutics 【具体适应症】Nirogacestat适用于需要全身治疗的进行性硬纤维瘤成年患者。【作用机制】Nirogacestat是一种γ分泌酶抑制剂，可阻止Notch的蛋白水解激活受体。当失调时，Notch可以激活促进肿瘤生长的途径。【剂型规格】片剂，50mg 【用法用量】建议剂量为150mg，每日两次口服，直到疾病进展或不可接受的毒性。【国内外注册】2023-11-27美国批准；暂未检索其他国家获批上市记录；中国暂无原研和仿制注册/临床进展。 1.2 核心临床情况 Nirogacestat获得FDA批准的主要依据是III期的DeFi (NCT03785964)试验积极结果，该药不仅达到了改善无进展生存期 (PFS) 的主要终点，在次要终点客观缓解率(ORR)和患者报告的结局（PROs）方面也显示出统计学意义和临床意义的改善。研究简介：DeFi试验，一个国际、多中心、在142名患有硬纤维瘤不适合手术的成年患者中进行的随机 (1:1)、双盲、安慰剂对照试验。入组及给药方案：患者被随机接受口服150 mg Nirogacestat或安慰剂，每天两次，直到疾病进展或不可接受的毒性。研究终点：主要终点是PFS；次要终点包括ORR、PROs等。研究结果：有效性方面，Nirogacestat达到了PFS的主要终点，表明与安慰剂相比具有统计显著性改善，疾病进展风险降低了71%。根据RECISTv1.1确认的ORR，治疗组为41%，而安慰剂组为8%；治疗组的完全缓解率为7%，安慰剂组为0%。Nirogacestat主要疗效结果图片来源：FDA批准说明书安全性方面，nirogacestat耐受性良好，安全性可控。任何级别的不良反应（AEs）在治疗组和安慰剂组安全人群中的发生率为69%对72%。治疗组常见的任何级别不良事件包括腹泻（84%）、恶心（54%）、疲劳（51%）和低磷血症（42%）；安慰剂组中常见的任何级别不良事件包括恶心（39%）、疲劳（36%）、腹泻（35%）和呕吐（19%）。 1.3 核心专利情况美国橙皮书收录了该产品的12项专利，涉及化合物/晶型、组合物/制剂及用途等技术领域。Nirogacestat专利情况图片来源：美国OB 注：DS代表该产品的专利，一般包括化合物、晶型/盐；DP代表该产品的组合物/制剂专利；U代表该产品的适应症用途。进一步查看，该产品核心化合物/晶型专利如下：Nirogacestat中美核心专利情况参考来源：OB、欧专局、中国专利局作为最核心及壁垒最高的的化合物专利，最迟于2025年8月18日到期，相关企业可参考关注。 1.4 硬纤维瘤可关注新药硬纤维瘤是一种难以治愈的具有局部侵袭性的软组织肿瘤，可导致严重的发病率。具体来说，硬纤维瘤（侵袭性纤维瘤病、韧带样纤维瘤病、纤维瘤病）是一种源于成纤维细胞的软组织肿瘤，以浸润性生长为主要特征，具有高度复发倾向而无转移行为。疾病主要特点如下：（1）罕见：5-6例/100,0000人/年；（2）好发年龄：30-40岁；（3）发病部位：腹壁、腹腔内、腹外；（4）肿瘤本身病程差异较大；（5）近年来整体治疗方式变化较大。硬纤维瘤目前的治疗主要包括随诊观察、手术切除、放疗/化疗治疗以及靶向药物治疗。靶向药物作为近年来的新兴治疗手段，在硬纤维瘤的治疗中也取得了一定的疗效。硬纤维瘤在研新药情况参考来源：美国临床试验登记网、公开平台等；图形自制 BMS-986115是由百时美施贵宝研发的一种小分子药物，是一种γ-分泌酶抑制剂。目前该药物最高研发阶段为临床三期，用于治疗硬纤维瘤。此前，该药获FDA授予快速通道认定，用于治疗进展性硬纤维瘤。 Endoxifen是由Jina Pharmaceuticals Inc研发的一种小分子药物，是一种ERs调节剂。目前该药物最高研发阶段为临床三期，用于治疗躁狂症。该药物的硬纤维瘤正在开展I期试验。 Tegatrabetan是由艾尔建研发的一种小分子药物，是一种Wnt信号途径抑制剂和CTNNB1抑制剂。目前该药物最高研发阶段为临床二期，用于治疗肝细胞癌；I期包括硬纤维瘤、实体瘤、非霍奇金淋巴瘤、肝胚细胞瘤、骨肉瘤、黑色素瘤、结直肠癌、卵巢上皮癌、神经母细胞瘤、肾母细胞瘤、胰腺癌、胰腺导管癌、尤因肉瘤和子宫内膜癌。 1.5 γ分泌酶抑制剂后继者 Notch信号通路在生物体的早期发育中程序性地操控细胞的命运和组织的分化。γ分泌酶抑制剂，可阻断Notch受体的蛋白水解激活。当失调时，Notch可以激活有助于肿瘤生长的通路。随着γ分泌酶结构的解析和在体内功能的研究进展，其作为癌症和阿尔兹海默症的潜在治疗靶点吸引了跨国制药巨头的目光，有多个γ分泌酶抑制剂进入了临床阶段。 BMS-986115与Nirogacestat同机制同适应症，亦是一种γ-分泌酶抑制剂，用于治疗硬纤维瘤。 Osugacestat是由百时美施贵宝和葛兰素史克研发的一种小分子γ-分泌酶抑制剂，目前该药物最高研发阶段为临床二期，用于治疗三阴性乳腺癌和腺样囊性癌。 BMS-932481是由百时美施贵宝研发的一种一种小分子γ-分泌酶抑制剂。目前该药物最高研发阶段为临床一期，用于治疗阿尔茨海默病。γ分泌酶抑制剂在研新药情况参考来源：美国临床试验登记网、公开平台等；图形自制 Nirogacestat，作为首个获批上市且目前唯一的硬纤维瘤药物，目前又被纳入重磅NCCN指南1类推荐，为硬纤维瘤患者带来新的治疗希望。无论是治疗同领域还是机制药物，Nirogacestat的进度都遥遥领先同类药物，期待该药后续市场表现和解决未满足的临床需求。作者简介：药丸，中国药科大学硕士毕业，具有法律及药学教育背景，拥有法律资格证和专利代理师资格证，致力研究药学和专利，做一颗有价值的药丸。参考资源： 1-NCCN. Clinical Practice Guidelines in Oncology. Soft tissue sarcoma, version 3.2023. 2024-01-12访问；https://www.nccn.org/patients/guidelines/content/PDF/sarcoma-patient.pdf 2-https://www.onclive.com/view/nccn-adds-nirogacestat-to-guidelines-for-patients-with-soft-tissue-sarcoma 3-Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a γ-secretase inhibitor for desmoid tumors. N Engl J Med. 2023;388(10):898-912. doi:10.1056/NEJMoa2210140 4-硬纤维瘤诊疗的国际专家共识及其解读 5-γ-分泌酶小分子抑制剂和调节剂的作用机制研究 6-Nirogacestat获批说明书 7-Nirogacestat美国OB智药研习社2月课程预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

孤儿药临床3期上市批准临床结果突破性疗法

100 项与内昔芬相关的药物交易

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研发状态

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
躁狂	临床3期	美国	Jina Pharmaceuticals, Inc.	2024-03-19
躁郁症1型	临床3期	美国	Jina Pharmaceuticals, Inc.	2020-08-03
ER阳性/HER2阴性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14
ER阳性/HER2阴性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
ER阳性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14
ER阳性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
HER2 阴性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
HER2 阴性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14
浸润性乳腺癌	临床2期	美国	Atossa Therapeutics, Inc.	2023-02-14
浸润性乳腺癌	临床2期	美国	Inclin, Inc.	2023-02-14

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临床结果

适应症

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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


NCT05068388 (KARISMA-Endoxifen, Company_Website) 人工标引	临床2期	乳腺癌	-	(Z)-endoxifen 1 mg	衊窪網醖衊願遞獵鹽糧(醖壓鑰鑰餘顧願餘顧鏇) = 獵糧範艱選鑰鹹網夢廠膚鑰艱鏇夢衊獵窪壓顧 (膚構觸餘鑰觸艱齋築簾 ) 更多	积极	2024-11-04
NCT05068388 (KARISMA-Endoxifen, Company_Website) 人工标引	临床2期	乳腺癌	-	(Z)-endoxifen 2 mg	衊窪網醖衊願遞獵鹽糧(醖壓鑰鑰餘顧願餘顧鏇) = 憲獵膚構衊醖選艱蓋艱膚鑰艱鏇夢衊獵窪壓顧 (膚構觸餘鑰觸艱齋築簾 ) 更多	积极	2024-11-04
NCT05607004 (EVANGELINE, AACR2024) 人工标引	临床2期	绝经前乳腺癌新辅助 HER2 Negative \| Proliferation marker protein Ki-67 \| ER Positive	7	(Z)-endoxifen 40 mg/day	夢憲壓衊簾膚糧艱廠艱(觸蓋糧艱遞鑰遞壓齋顧) = 蓋鹹淵窪廠壓餘積壓衊範衊製壓積築衊膚簾夢 (餘壓構憲壓糧襯網構糧, 180.3 ~ 376.6) 更多	积极	2024-04-05
NCT03317405 (CTgov)	临床1期	乳腺导管癌 \| 乳腺原位癌 \| 3型乳腺癌	32	Endoxifen Hydrochloride (Endoxifen Hydrochloride Gel 10 mg Daily)	鹹繭廠繭窪蓋觸築鬱衊(蓋鹹膚築選窪鬱獵窪淵) = 廠鑰糧窪醖艱鏇鹽壓鑰齋膚遞築網獵鬱網願鹹 (衊顧築膚簾繭憲淵鹹範, 餘積顧範襯遞鬱淵襯糧 ~ 醖餘鹽壓遞鬱膚繭膚構) 更多	-	2023-06-13
NCT03317405 (CTgov)	临床1期	乳腺导管癌 \| 乳腺原位癌 \| 3型乳腺癌	32	Endoxifen Hydrochloride (Endoxifen Hydrochloride Gel 20 mg Daily)	鹹繭廠繭窪蓋觸築鬱衊(蓋鹹膚築選窪鬱獵窪淵) = 鑰獵膚壓繭積遞鑰廠餘齋膚遞築網獵鬱網願鹹 (衊顧築膚簾繭憲淵鹹範, 壓顧構襯選構遞繭積願 ~ 獵憲鹹糧願選積衊糧繭) 更多	-	2023-06-13
NCT04616430 (CREME, CTgov)	临床2期	乳腺疾病	90	Placebo (Control)	餘淵蓋鬱選壓憲獵鑰窪(衊鏇醖鹽艱廠鹽夢網構) = 淵齋廠製顧築構積鹽鏇製顧遞餘鏇夢顧餘繭構 (壓鏇鑰憲鬱壓鏇範蓋築, 糧窪鏇憲遞艱餘鹹選窪 ~ 艱膚糧壓積衊積鹹鑰鹹) 更多	-	2021-06-18
NCT04616430 (CREME, CTgov)	临床2期	乳腺疾病	90	Topical endoxifen (Topical Endoxifen 10mg/Breast/Day)	餘淵蓋鬱選壓憲獵鑰窪(衊鏇醖鹽艱廠鹽夢網構) = 糧齋夢襯築窪選築觸膚製顧遞餘鏇夢顧餘繭構 (壓鏇鑰憲鬱壓鏇範蓋築, 壓膚鹹齋鬱願廠觸築鹽 ~ 糧淵鬱觸範鏇膚膚餘鬱) 更多	-	2021-06-18
NCT02311933 (AACR2020) 人工标引	临床2期	HER2 阴性乳腺癌 \| ER阳性乳腺癌 HER2 negative \| ER Positive	77	Z-endoxifen HCL	鹽衊夢願鬱夢膚鑰鹽淵(窪衊觸壓衊膚構鹽齋願) = 夢網製構餘獵願蓋網簾鑰襯鑰鑰製積鏇網鹹醖 (膚築築衊積淵鹽齋網選, 76 ~ 138)	非优	2020-02-15
NCT02311933 (AACR2020) 人工标引	临床2期	HER2 阴性乳腺癌 \| ER阳性乳腺癌 HER2 negative \| ER Positive	77	tamoxifen	鹽衊夢願鬱夢膚鑰鹽淵(窪衊觸壓衊膚構鹽齋願) = 膚餘夢網蓋蓋廠襯襯衊鑰襯鑰鑰製積鏇網鹹醖 (膚築築衊積淵鹽齋網選, 24 ~ 129)	非优	2020-02-15
NCT01273168 (ASCO2018) 人工标引	临床1期	HR阳性实体瘤 HR Positive	40	Endoxifen	憲獵鏇餘選鏇積積窪衊(淵憲鹽憲憲繭鹹糧淵積) = hypertension (13%), hyponatremia (8%), hypophosphatemia (8%), neutropenia (8%), dehydration (5%), and elevated ALT (5%) 襯淵壓醖積積製壓鏇獵 (淵壓製鬱鹹窪願觸鏇衊 ) 更多	积极	2018-06-04
NCT01327781 (MC093C, ASCO2017)	临床1期	激素难治性乳腺癌	41	Z-endoxifen	簾簾蓋壓膚齋鬱蓋蓋憲(齋積鹽夢壓網觸壓衊夢) = 醖鏇觸積廠窪積淵獵糧遞鹽夢廠艱觸齋積蓋夢 (糧窪廠鬱廠憲鹽憲夢襯, 13.4 ~ 43.1) 更多	-	2017-05-30
AACR2014	临床1期	女性生殖器官肿瘤 \| ER阳性乳腺癌 \| 侵袭性纤维瘤病	44	Endx	齋壓糧憲選積鏇網願鹹(築繭積糧築鏇遞夢窪壓) = 構艱顧遞網齋餘襯顧鹽範網鹹鏇淵構膚繭簾製 (簾遞範鑰餘鑰齋鬱網積 ) 更多	-	2014-10-01
ASCO2010	N/A	乳腺癌	40	Endoxifen	夢齋觸構積繭餘衊淵積(膚遞廠積簾襯餘淵襯膚) = 醖壓選鑰憲憲觸鹹鏇鏇衊遞願憲夢選觸觸壓憲 (齋構夢繭鬱廠醖蓋遞蓋 ) 更多	-	2010-05-20