A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study of Buntanetap in Participants With Mild to Moderate Alzheimer's Disease

The purpose of this study is to measure efficacy and safety of three different doses of buntanetap/Posiphen compared with placebo in participants with mild to moderate Alzheimer's disease.
Study details include:
The double-blind treatment duration will include a screening period of up to 42 days followed by 12 weeks of treatment at home.
The study duration will be 4-5 months. There will be 4 in-clinic visits and 1 phone call.

开始日期2023-04-01

申办/合作机构

Annovis Bio, Inc.

NCT05357989 / Completed临床3期

A 6-month Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial Investigating the Efficacy, Safety, and Tolerability of Two Different Doses of Buntanetap or Placebo in Patients With Early Parkinson's Disease

The purpose of this study is to measure safety and efficacy of buntanetap/posiphen capsules compared with placebo capsules in participants with early PD.
Study details include:
The study duration will be up to 7-8 months.
The double-blind treatment duration will be up to 6 months.
There will be 5 in-clinic visits and 7 phone calls

开始日期2022-08-03

申办/合作机构

Annovis Bio, Inc.

[+1]

NCT04524351 / Completed临床1/2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Posiphen® in Subjects With Early Alzheimer's Disease (AD) or Early Parkinson's Disease (PD)

Annovis is conducting a clinical study to investigate Posiphen in patients with Early Alzheimer's Disease (AD) and Early Parkinson's Disease (PD). Investigators are looking to recruit 68 patients in two parts of the study. In Part one of the study Investigators will recruit 14 AD and 14 PD patients who will either receive placebo (an inert pill which looks like the study drug) or the study drug Posiphen, both taken daily. In Part two of the study Investigators will recruit 40 PD patients who will receive different strengths of the study drug Posiphen taken daily. Patients will be required to come to the site for 3 face to face visits and have 4 phone calls, tests include but are not limited to, blood and CSF (spinal fluid) sampling, cognitive assessments, clinical examinations and laboratory safety tests. Primarily the Investigators are looking for the safety and tolerability of Posiphen, although Investigators will also evaluate the activity of Posiphen by a number of different biomarkers measuring pathway and target engagements.

开始日期2020-08-14

申办/合作机构

Annovis Bio, Inc.

[+1]

100 项与 Buntanetap 相关的临床结果

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100 项与 Buntanetap 相关的转化医学

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100 项与 Buntanetap 相关的专利（医药）

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项与 Buntanetap 相关的文献（医药）

2024-04-01·SLAS discovery : advancing life sciences R & D

Real-time thiol detection in iPSC-derived neuron cultures using SemKur-IM, a novel fluorescent dithio probe

Article

作者: Alvarez, Roxanne ; Sem, Daniel S ; Kurfis, Jayson ; Hendrickson, Michael

Neurological disorders associated with inflammation and oxidative stress show reduced glutathione (GSH) levels in the human brain. Drug discovery efforts and pharmacological studies would benefit from tools (e.g. chemical probes) that detect changes to oxidative stress, from the perspective of physiologically-relevant reporters like cellular thiols, including GSH. To this end, we have developed a fluorescence visualization assay using iPSC-derived cortical glutamatergic neurons that were loaded with 25 μM of a novel thiol-detection fluorescent probe, SemKur-IM. This probe enables visualization of cellular thiol level changes in the neuronal somas and neurites, in response exposure to N-acetyl-cysteine (NAC). Cellular thiol redox state was observed to change, based on an increase in green fluorescence (485 nm excitation maximum; 525 nm emission maximum) due to changes in thiol levels, from 0 to 40 mM. Interestingly, prior to treatment with NAC, cells did not appear to have significant levels of reduced thiols. Our studies demonstrate the utility of SemKur-IM in the detection of thiol levels in live cells in response to chemical exposures, such as from drugs that return the cell to a healthier reduced state. An initial application to screening the effects of an Alzheimer's disease drug candidate, Posiphen, using fluorescence cell sorting is presented. Other potential applications include high throughput screening of central nervous system (CNS) drugs thought to work by affecting cellular redox state in neurons.

2022-02-11·ACS pharmacology & translational science

In Silico and Ex Vivo Analyses of the Inhibitory Action of the Alzheimer Drug Posiphen and Primary Metabolites with Human Acetyl- and Butyrylcholinesterase Enzymes

Article

作者: Furqan, Tiyyaba ; Tweedie, David ; Greig, Nigel H. ; Hasan Mahmood, Muhammad Sibte ; Kamal, Mohammad A. ; Batool, Sidra

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Ongoing research to develop AD treatments has characterized multiple drug targets including the cholinergic system, amyloid-β peptide, phosphorylated tau, and neuroinflammation. These systems have the potential to interact to either drive or slow AD progression. Promising agents that simultaneously impact many of these drug targets are the AD experimental drug Posiphen and its enantiomer phenserine that, currently, are separately being evaluated in clinical trials. To define the cholinergic component of these agents, the anticholinesterase activities of a ligand dataset comprising Posiphen and primary metabolites ((+)-N1-norPosiphen, (+)-N8-norPosiphen, and (+)-N1,N8-bisnorPosiphen) were characterized and compared to those of the enantiomer phenserine. The "target" dataset involved the human cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Binding interactions between the ligands and targets were analyzed using Autodock 4.2. The computationally determined inhibitory action of these ligands was then compared to ex vivo laboratory-measured values versus human AChE and BChE. While Posiphen lacked AChE inhibitory action, its major and minor metabolites (+)-N1-norPosiphen and (+)-N1,N8-bisnorPosiphen, respectively, possessed modest AChE inhibitory activity, and Posiphen and all metabolites lacked BChE action. Phenserine, as a positive control, demonstrated AChE-selective inhibitory action. In light of AChE inhibitory action deriving from a major and minor Posiphen metabolite, current Posiphen clinical trials in AD and related disorders should additionally evaluate AChE inhibition; particularly if Posiphen should be combined with a known anticholinesterase, since this drug class is clinically approved and the standard of care for AD subjects, and excessive AChE inhibition may impact drug tolerability.

2021-02-01·Alzheimer's & dementia : the journal of the Alzheimer's Association1区 · 医学

Targeting increased levels of APP in Down syndrome: Posiphen‐mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model

1区 · 医学

Article

作者: Salehi, Ahmad ; Overk, Cassia ; Maccecchini, Maria ; Nguyen, Phuong D. ; Mobley, William C. ; Pearn, Matthew L. ; Kleschevnikov, Alexander M. ; Chen, Xu‐Qiao

Abstract:

Objective:

Recent clinical trials targeting amyloid beta (Aβ) and tau in Alzheimer's disease (AD) have yet to demonstrate efficacy. Reviewing the hypotheses for AD pathogenesis and defining possible links between them may enhance insights into both upstream initiating events and downstream mechanisms, thereby promoting discovery of novel treatments. Evidence that in Down syndrome (DS), a population markedly predisposed to develop early onset AD, increased APP gene dose is necessary for both AD neuropathology and dementia points to normalization of the levels of the amyloid precursor protein (APP) and its products as a route to further define AD pathogenesis and discovering novel treatments.

Background:

AD and DS share several characteristic manifestations. DS is caused by trisomy of whole or part of chromosome 21; this chromosome contains about 233 protein‐coding genes, including APP. Recent evidence points to a defining role for increased expression of the gene for APP and for its 99 amino acid C‐terminal fragment (C99, also known as β‐CTF) in dysregulating the endosomal/lysosomal system. The latter is critical for normal cellular function and in neurons for transmitting neurotrophic signals.

New/updated hypothesis:

We hypothesize that the increase in APP gene dose in DS initiates a process in which increased levels of full‐length APP (fl‐APP) and its products, including β‐CTF and possibly Aβ peptides (Aβ42 and Aβ40), drive AD pathogenesis through an endosome‐dependent mechanism(s), which compromises transport of neurotrophic signals. To test this hypothesis, we carried out studies in the Ts65Dn mouse model of DS and examined the effects of Posiphen, an orally available small molecule shown in prior studies to reduce fl‐APP. In vitro, Posiphen lowered fl‐APP and its C‐terminal fragments, reversed Rab5 hyperactivation and early endosome enlargement, and restored retrograde transport of neurotrophin signaling. In vivo, Posiphen treatment (50 mg/kg/d, 26 days, intraperitoneal [i.p.]) of Ts65Dn mice was well tolerated and demonstrated no adverse effects in behavior. Treatment resulted in normalization of the levels of fl‐APP, C‐terminal fragments and small reductions in Aβ species, restoration to normal levels of Rab5 activity, reduced phosphorylated tau (p‐tau), and reversed deficits in TrkB (tropomyosin receptor kinase B) activation and in the Akt (protein kinase B [PKB]), ERK (extracellular signal‐regulated kinase), and CREB (cAMP response element–binding protein) signaling pathways. Remarkably, Posiphen treatment also restored the level of choline acetyltransferase protein to 2N levels. These findings support the APP gene dose hypothesis, point to the need for additional studies to explore the mechanisms by which increased APP gene expression acts to increase the risk for AD in DS, and to possible utility of treatments to normalize the levels of APP and its products for preventing AD in those with DS.

Major challenges for the hypothesis:

Important unanswered questions are: (1) When should one intervene in those with DS; (2) would an APP‐based strategy have untoward consequences on possible adaptive changes induced by chronically increased APP gene dose; (3) do other genes present on chromosome 21, or on other chromosomes whose expression is dysregulated in DS, contribute to AD pathogenesis; and (4) can one model strategies that combine the use of an APP‐based treatment with those directed at other AD phenotypes including p‐tau and inflammation.

Linkage to other major theories:

The APP gene dose hypothesis interfaces with the amyloid cascade hypothesis of AD as well as with the genetic and cell biological observations that support it. Moreover, upregulation of fl‐APP protein and products may drive downstream events that dysregulate tau homeostasis and inflammatory responses that contribute to propagation of AD pathogenesis.

104

项与 Buntanetap 相关的新闻（医药）

2024-09-05

·GlobeNewswire-Health Care

Annovis Bio (NYSE: ANVS) to Present at H.C. Wainwright 26th Annual Global Investment Conference

MALVERN, Pa., Sept. 05, 2024 (GLOBE NEWSWIRE) -- via IBN – Annovis Bio Inc. (NYSE: ANVS) (“Annovis” or the “Company”), a late-stage clinical drug platform company developing novel therapies for neurodegenerative diseases, today announced that Maria L. Maccecchini, Ph.D., Founder, President, and CEO of Annovis Bio, will participate in the H.C. Wainwright 26th Annual Global Investment Conference, held both virtually and in person at the Lotte New York Palace Hotel in New York City, September 9-11, 2024. Event Details Company Presentation: Date: Tuesday, September 10, 2024Time: 8:00 - 8:30 a.m. Eastern Time (ET) Panel Participation: Topic: "Non-amyloid Approaches in Alzheimer’s Disease"Date: Tuesday, September 10, 2024Time: 2:00 - 3:00 p.m. ET During the Company presentation, Dr. Maccecchini will provide an overview of Annovis’ recent advancements and strategic direction, followed by a Q&A session. In addition, Dr. Maccecchini will participate in a panel discussion focusing on innovative non-amyloid approaches in Alzheimer’s disease, featuring representatives from Annovis Bio (ANVS), Anavex Life Sciences Corp. (AVXL), and Longeveron Inc. (LGVN). Please note that the presentation schedule is subject to change. Attendees are encouraged to check the conference agenda for the most current information. To schedule a one-on-one meeting with Dr. Maccecchini, please use the conference portal or contact meetings@hcwco.com. For more information, please visit the conference website. About Annovis Bio, Inc. Headquartered in Malvern, Pennsylvania, Annovis Bio Inc. is dedicated to addressing neurodegeneration in diseases such as AD and PD. The company’s innovative approach targets multiple neurotoxic proteins, aiming to restore brain function and improve the quality of life for patients. For more information, visit www.annovisbio.com and follow us on LinkedIn, YouTube, and X. Investor Alerts Interested investors and shareholders are encouraged to sign up for press releases and industry updates by registering for Email Alerts at https://www.Annovisbio.com/email-alerts. Forward-Looking Statements This press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements include, but are not limited to, the Company's plans related to clinical trials. Forward-looking statements are based on current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such risks and uncertainties include, but are not limited to, those related to patient enrollment, the effectiveness of Buntanetap, and the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety, and tolerability of Buntanetap. Additional risk factors are detailed in the Company's periodic filings with the SEC, including those listed in the "Risk Factors" section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. All forward-looking statements in this press release are based on information available to the Company as of the date of this release. The Company expressly disclaims any obligation to update or revise its forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law. Contact Information: Annovis Bio Inc. 101 Lindenwood Drive Suite 225 Malvern, PA 19355 www.annovisbio.com Investor Contact: Scott McGowan InvestorBrandNetwork (IBN) Phone: 310.299.1717 IR@annovisbio.com

2024-08-15

·GlobeNewswire-Health Care

Annovis Bio Reports Second Quarter Financial Results and Provides Business Update

MALVERN, Pa., Aug. 15, 2024 (GLOBE NEWSWIRE) -- via IBN -- Annovis Bio Inc. (NYSE: ANVS) (“Annovis” or the “Company”), a clinical-stage drug platform company developing novel therapies for neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), today announced financial results for the second quarter ended June 30, 2024, and provided a business update. "The recent months have been productive for our company," said Maria Maccecchini, Ph.D., Founder, President, and CEO of Annovis Bio. "We've completed pivotal Phase 2/3 Alzheimer's and Phase 3 Parkinson's studies, both of which revealed very encouraging data for buntanetap. Additionally, we’ve introduced a new crystalline form of buntanetap with improved properties, further strengthening our IP portfolio. These milestones position us strongly as we move closer to providing much-needed treatments to patients." Clinical Trial Updates Alzheimer’s Disease (AD) On April 29, 2024, Annovis Bio reported data from its completed Phase 2/3 AD study. The results showed that buntanetap significantly improved cognition in patients with early AD, with a 3.3-point improvement on the ADAS-Cog11 test after three months of treatment, compared to a 0.3-point improvement in the placebo group.The study also indicated a trend toward reduced plasma tau protein levels, consistent with previous findings, suggesting a potential disease-modifying effect of buntanetap.A follow-up analysis, on June 11, 2024, demonstrated that buntanetap was particularly effective in improving cognition among high-risk APOE4 carriers, showing a 3.15-point improvement.Bunetanetap was found to be equally safe in both APOE4 carriers and non-carriers, with no instances of Amyloid-Related Imaging Abnormalities (ARIA) observed. Parkinson’s Disease (PD) On July 2, 2024, Annovis Bio announced the Phase 3 PD study data, which revealed that buntanetap led to significant improvements in both the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and cognition across several PD subpopulations. Buntanetap showed a particularly strong response in individuals diagnosed with PD for more than three years as well as in those with postural instability and gait disorder (PIGD). Moreover, buntanetap halted cognitive decline in all enrolled patients and improved cognition in those with mild dementia, mirroring the positive results observed in our AD studies. Second Quarter 2024 Financial Results Annovis Bio received $7.1 million net cash from exercises of Canaccord warrants in July 2024. Cumulatively to date, Annovis Bio received $7.0 million net cash from ELOC facility announced in April 2024.The Company’s cash and cash equivalents totaled $4.0 million as of June 30, 2024, compared to $5.7 million as of December 31, 2023. The Company had 11.7 million shares of common stock outstanding as of June 30, 2024. After recent warrant exercises and ELOC share placements, as of August 14, 2024, Annovis Bio had cash and cash equivalents of $12.1 million, which we believe is sufficient to support operations through the planned AD and PD FDA meetings in Fall and continuing until the initiation of the two pivotal studies planned. Total operating expenses for the three months ended June 30, 2024, were $7.8 million, which included research and development expenses of $5.8 million and general and administrative expenses of $2.0 million. This compares to total operating expenses for the three months ended June 30, 2023, of $9.8 million, which included research and development expenses of $8.2 million and general and administrative expenses of $1.5 million. Annovis Bio reported a $0.44 basic and diluted net loss per common share for the three months ended June 30, 2024. This compares to a $1.07 basic and diluted net loss per common share for the three months ended June 30, 2023. Patents The Company filed a new composition of matter patent covering a novel crystal form of buntanetap and its use for treating and/or preventing various neurodegenerative conditions. The new crystalline form offers significant advantages over the less structured, old semi-crystalline form, including better solubility and stability as well as an additional 20 years of patent life. The Company has filed a provisional patent for the methods of manufacturing this new crystalline form, covering the entire synthesis process—from basic starting materials to finished GMP product—suitable for large-scale manufacturing at ton quantities.On July 16, 2024, Annovis Bio received FDA approval to continue the Phase 3 development with the new crystal form. Additionally, the Company was granted a U.S. patent for the use of buntanetap in the treatment of acute traumatic brain injury. Team Updates On July 9, 2024, Annovis Bio announced the expansion of its team with several key appointments: Mark White as Chief Business Officer, Alexander Morin as Director of Strategic Communications, Hilda Maibach as Senior Vice President of Statistics, and Blake Jensen as Head of Quality. Other Achievements On May 21, 2024, the Company shared a new scientific article focused on the similarities and differences in buntanetap’s pharmacokinetic behavior between several animal models and humans, summarizing years of research. On August 6, 2024, Annovis Bio revealed new preclinical data showing a synergistic improvement on cognition when combining buntanetap with the GLP-1 agonist Trulicity®. About Annovis Bio, Inc.Headquartered in Malvern, Pennsylvania, Annovis Bio Inc. is dedicated to addressing neurodegeneration in diseases such as AD and PD. The company’s innovative approach targets multiple neurotoxic proteins, aiming to restore brain function and improve the quality of life for patients. For more information, visit www.annovisbio.com and follow us on LinkedIn, YouTube, and X. Investor AlertsInterested investors and shareholders are encouraged to sign up for press releases and industry updates by registering for Email Alerts at https://www.Annovisbio.com/email-alerts. Forward-Looking StatementsThis press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements include, but are not limited to, the Company's plans related to clinical trials. Forward-looking statements are based on current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such risks and uncertainties include, but are not limited to, those related to patient enrollment, the effectiveness of Buntanetap, and the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety, and tolerability of Buntanetap. Additional risk factors are detailed in the Company's periodic filings with the SEC, including those listed in the "Risk Factors" section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. All forward-looking statements in this press release are based on information available to the Company as of the date of this release. The Company expressly disclaims any obligation to update or revise its forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law. Contacts Annovis Bio, Inc. 101 Lindenwood Drive Suite 225 Malvern, PA 19355 www.annovisbio.com Investor Contact Scott McGowan InvestorBrandNetwork (IBN) Phone: 310.299.1717 ‍IR@annovisbio.com Investor Website

临床3期临床结果高管变更财报

2024-08-08

·药时代

近一个月药物研究积极进展与消极进展概览

积极进展据统计，在检索时间范围内，共有12个药物的临床试验数据取得积极进展，处于NDA、Ⅲ期临床、Ⅱ期临床、Ⅰ期临床研究阶段的药物分别有1、5、5和1个（表1）。这些药物涉及的适应症包括糖尿病肾病、艾滋病预防、膀胱癌、帕金森病（PD）、重性抑郁障碍（MDD）、胰腺炎、头颈癌、肌萎缩侧索硬化症（ALS）等，以下对部分药物进行简介。表1：近一个月（2024年6月16日～2024年7月15日）临床试验数据积极的药物 01 Amvuttra Amvuttra是一种在研、皮下给药的RNAi治疗药物，开发用于治疗ATTR淀粉样变性，包括遗传性ATTR和野生型ATTR淀粉样变性，通过靶向和沉默特定的mRNA，阻断野生型和变体转甲状腺素蛋白的产生。这款疗法通过Alnylam公司的增强稳定化学（ESC）-GalNAc偶联递送平台设计，增加了其治疗效力和代谢稳定性，允许以每季度的频率进行皮下注射，并具有减少至每半年注射一次的潜力。Amvuttra获得欧盟与美国在治疗转甲状腺素蛋白介导淀粉样变性的孤儿药资格，并在2022年6月获得美国FDA批准治疗遗传性ATTR淀粉样变性成人患者的多发性神经病变。2024年6月24日，Alnylam公司报告了Vutrisiran HELIOS-B Ⅲ期研究的积极结果，在总体治疗和单药治疗人群中的主要终点和所有次要终点均达到统计学意义：在总体人群和单一疗法人群中，全因死亡率和复发性心血管事件的复合死亡率分别降低了28%和33%；在预先指定的次要终点中，总体人群和单一疗法人群的全因死亡率分别降低了36%和35%；在6分钟步行试验（6MWT）、堪萨斯城心肌病问卷-总体总结评分（KCCQ-OSS）和纽约心脏协会（NYHA）分级（衡量疾病进展的关键指标）方面显示出临床显著疗效；在所有关键亚组中观察到一致的疗效；显示出令人鼓舞的安全性。 02 Buntanetap 2024年7月，Annovis Bio公司公布其在研小分子Buntanetap（又名Posiphen，研发代号ANVS401）在治疗PD的Ⅲ期研究新数据，显示Buntanetap在改善早期PD患者运动和非运动活动以及改善认知功能方面安全有效。Buntanetap通过抑制多种神经毒性蛋白，包括β淀粉样蛋白β、tau蛋白、α-突触核蛋白和TDP43蛋白，来缓解神经退行性变。所有入组患者分析显示，安慰剂组《简易智力状态检查量表（MMSE）》平均得分出现下降，Buntanetap 10mg和20mg剂量组MMSE平均得分维持在基线水平。亚组分析显示，轻度痴呆患者（MMSE得分20-26），安慰剂组MMSE平均得分出现下降，Buntanetap 10mg剂量组MMSE平均得分维持在基线水平，Buntanetap 20mg剂量组MMSE平均得分得到改善。被诊断PD超过3年的患者，安慰剂组《MDS统一帕金森病评定量表（MDS-UPDRS）》评分第Ⅱ部分与Buntanetap 10mg和20mg剂量组相比出现恶化。Buntanetap 20mg剂量组MDS-UPDRS第Ⅱ部分、第Ⅲ部分、第Ⅱ部分+第Ⅲ部分和总分得到改善。 03 Imfinzi Imfinzi是一种人源化单克隆抗体，它与PD-L1蛋白结合并阻断PD-L1与PD-1及CD80蛋白的相互作用，从而对抗肿瘤的免疫逃逸策略，并解除对免疫反应的抑制，增强免疫系统杀伤癌细胞的能力。肌层浸润性膀胱癌（MIBC）指的是肿瘤侵入膀胱肌壁但未发生远处转移的膀胱癌，约占总体患者的四分之一。近期，阿斯利康（AstraZeneca）公司公布了Imfinzi Ⅲ期临床试验NIAGARA的积极结果。分析显示，与单独新辅助化疗相比，其重磅免疫疗法Imfinzi与化疗联用可在统计学与临床上显著延长MIBC患者的总生存期（OS）。根据新闻稿，这是可在手术前并在手术后使用可延长膀胱癌患者生存期的首个免疫治疗方案。在MIBC的治疗中，目前约有11.7万名患者接受标准治疗。标准治疗包括新辅助化疗和根治性膀胱切除手术（Cystectomy）。然而，即使在切除膀胱后，患者仍然面临高复发率和较差的预后。 NIAGARA是一项随机、开放标签、多中心、全球Ⅲ期临床试验，评估Imfinzi在根治性膀胱切除术前后治疗MIBC患者的治疗效果。在该试验中，1063名患者被随机分配在膀胱切除手术前接受Imfinzi联合化疗或单独化疗，术后则接受Imfinzi或不再进行进一步治疗。分析显示，Imfinzi联合化疗相比单独新辅助化疗，在MIBC患者中的无事件生存期（EFS）和OS这两个主要终点上均表现出统计学显著且具临床意义的改善。Imfinzi总体耐受性良好，在新辅助和辅助治疗中均未观察到新的安全问题。Imfinzi和新辅助化疗联合的安全性特征与已知的各药物特征一致。消极进展据统计，在检索时间范围内，共有7个药物的临床试验数据进展不佳（表1），其研究阶段分别为Ⅲ期临床和暂停。这些药物的适应症涉及癫痫、非小细胞肺癌（NSCLC）、三阴性乳腺癌（TNBC）、软组织肉瘤、肺动脉高压（PAH）和肺高血压（PH）。以下对其中部分药物的研究进展不佳原因进行简要介绍。表1：近一个月（2024年6月16日～2024年7月15日）临床试验数据不佳的药物 01 / Soticlestat 2024年6月17日，武田和Ovid Therapeutics共同公布了Soticlestat（TAK-935）治疗癫痫的两项Ⅲ期SKYLINE和SKYWAY研究的初步数据。Soticlestat是一款潜在“First-in-class”的CH24H抑制剂，CH24H是一种主要在大脑中表达的酶，可将胆固醇分解为24-S羟基胆固醇（24HC），从而降低谷氨酸能过度兴奋性。SKYLINE研究旨在评估Soticlestat+标准治疗相较于安慰剂+标准治疗在Dravet综合征患者中的疗效。与安慰剂相比，Soticlestat错过了惊厥性癫痫发作频率的主要终点（p=0.06）。在6个关键次要终点中，Soticlestat均显示出有临床意义和名义上显著（Nominally significant）的结果（所有p值均≤0.008）。在另一项针对难治性Lennox-Gastaut综合征患者的SKYWAY研究中，与安慰剂相比，该药物未能降低MMD癫痫发作频率。在SKYLINE和SKYWAY两项研究中，Soticlestat的耐受性普遍良好，其安全性与之前的研究结果一致。Dravet综合征（DS）和Lennox-Gastaut综合征（LGS）属于发育性和癫痫性脑病（DEE），这是罕见的癫痫综合征，通常在婴儿期或儿童早期变得明显，并对许多抗癫痫药物高度耐药。Ⅱ期ELEKTRA研究中，与安慰剂相比，Soticlestat使DS和LGS联合研究人群的癫痫发作次数在整个治疗期间较基线显著减少（p=0.002）。在DS队列中，与安慰剂组相比，Soticlestat组的癫痫发作频率也较基线显著降低（p=0.0007）。武田将与监管机构讨论这些研究产生的全部数据，以确定下一步措施。 02 / Truqap 近日，阿斯利康宣布，其AKT抑制剂Truqap（Capivasertib）在全人群或携带特定标志物改变的亚组患者的Ⅲ期临床试验中，联合紫杉醇一线治疗局部晚期或转移性TNBC均未达到OS的双重主要终点。Capivasertib是一款AKT1/2/3高效选择性抑制剂。2023年11月，Capivasertib获FDA批准上市，用于治疗激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）局部晚期或转移性乳腺癌患者，这些患者在接受内分泌基础方案治疗过程中或之后疾病复发或进展。此次这项研究为一项CAPItello-290 Ⅲ期临床试验，旨在评估Truqap化疗组合在特定TNBC患者中的潜在一线治疗效果。研究共涉及923例患者，并且特别评估了两个主要终点：（1）整体患者的OS；（2）携带PIK3CA、AKT1或PTEN生物标志物变异的肿瘤患者亚组的OS改善情况。此次阿斯利康在其公告中并未提供具体数据，只透露Capivasertib化疗组合在总研究人群或携带PIK3CA、AKT1或PTEN基因特定突变的患者亚组中，均未能显著提高OS。尽管如此，阿斯利康表示将继续在整个Truqap临床开发项目中进行深入研究。 03 / Tiragolumab 2024年7月4日，罗氏宣布Ⅱ/Ⅲ期SKYSCRAPER-06研究未达到主要终点，该研究旨在评估Tiragolumab+Tecentriq（Atezolizumab）+化疗vs Pembrolizumab+化疗一线治疗局部晚期不可切除或转移性非鳞状NSCLC患者。该研究的主要终点无进展生存期（PFS）的风险比（HR）为1.27，OS的HR为1.33。在意向治疗人群（包括Ⅱ期和Ⅲ期队列）中，Tiragolumab联合组的疗效在PFS和OS方面均低于对照组。总体安全性与之前观察到的Tiragolumab联合Tecentriq和化疗的安全性保持一致，没有发现新的或意想不到的结果。基于这些结果，罗氏将取消患者和研究人员的盲法，并打算停止这项研究。此外，根据研究结果，罗氏将对正在进行的Tiragolumab项目所需的任何相关变更进行评估。此前，Tiragolumab已在临床试验中多次折戟。 04 / Cosela 近日，G1 Therapeutics宣布其针对肺癌的药物Cosela（Trilaciclib）在一项关键的Ⅲ期临床试验PRESERVE 2中未能达到预期效果，这项试验旨在评估该药物作为一线治疗转移性TNBC的疗效，但其主要的评估指标OS未能实现预定目标。鉴于这一结果，G1 Therapeutics决定终止PRESERVE 2试验，并停止对Trilaciclib在一线TNBC适应症上的进一步投资，同时对公司结构进行了调整。Trilaciclib是一种CDK4/6抑制剂，主要用于减轻化疗引起的骨髓抑制。在PRESERVE 2研究中，Trilaciclib与吉西他滨和卡铂的联合治疗并未在意向治疗（ITT）人群中（共187名患者）展现出统计学上的显著疗效，HR为0.91，p值为0.884。尽管Trilaciclib联合治疗组的中位OS为17.4个月，略低于对照组的17.8个月，但这一差异并未达到统计学意义。此外，研究还观察到不同地区和接受不同后续治疗的患者之间存在疗效差异，这些数据将被进一步分析。在安全性方面，Trilaciclib的安全性与之前的研究结果一致，未发现新的安全问题。该药物显示出骨髓保护的潜力，特别是在减少严重中性粒细胞减少症的发生率方面，治疗组中仅有8%的患者出现这一症状，而对照组的发生率则高达29%。Trilaciclib在2021年2月获得了FDA的批准，用于治疗小细胞肺癌（ES-SCLC）成人患者的骨髓抑制。作为G1 Therapeutics的旗舰产品，Trilaciclib在小细胞肺癌治疗领域的成功促使公司将其在TNBC治疗领域的研究作为战略重点。然而，一线TNBC治疗的失败迫使G1 Therapeutics重新评估其在乳腺癌领域的战略，并决定将重点放回到ES-SCLC业务的扩展上，以期在2025年实现公司的盈利目标。值得注意的是，先声药业于2020年8月引进了Trilaciclib，并在2022年7月获得了NMPA的批准，用于治疗接受含铂类药物联合依托泊苷方案的ES-SCLC患者，以预防化疗引起的骨髓抑制。尽管在一线TNBC治疗上的尝试未能成功，但这并未影响G1 Therapeutics对Trilaciclib的商业前景的预期。公司预计，到2024年，Trilaciclib的净销售额将在6000万至7000万美元之间。【参考资料】 1. Informa数据库, 检索日期: 2024年7月20日. 2. Insight数据库, 检索日期: 2024年7月20日. 3. 药渡数据库，检索日期: 2024年7月20日. 4. 药明康德、BioArt、学术经纬、医药魔方、奇点网等网络公开资源. 封面图来源：123rf 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 简评2024年北京与上海支持创新药发展新政策的同与异当ADC叩响 “痴呆症” 的大门成立九年的Biotech，悄然倒闭！点击这里，发现价值信息！

临床3期孤儿药临床成功信使RNA临床2期

100 项与 Buntanetap 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床3期	美国	Annovis Bio, Inc.	2023-04-01
帕金森病	临床3期	欧盟	Annovis Bio, Inc.	2023-02-08
帕金森病（青年型、早发型）	临床3期	美国	Annovis Bio, Inc.	2022-08-03
帕金森病（青年型、早发型）	临床3期	德国	Annovis Bio, Inc.	2022-08-03
帕金森病（青年型、早发型）	临床3期	匈牙利	Annovis Bio, Inc.	2022-08-03
帕金森病（青年型、早发型）	临床3期	意大利	Annovis Bio, Inc.	2022-08-03
帕金森病（青年型、早发型）	临床3期	波兰	Annovis Bio, Inc.	2022-08-03
帕金森病（青年型、早发型）	临床3期	西班牙	Annovis Bio, Inc.	2022-08-03
认知功能障碍	临床2期	美国	Annovis Bio, Inc.	2009-05-26
路易体病	临床2期	-	Annovis Bio, Inc.	-

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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


NCT05357989 (Biospace) 人工标引	临床3期	帕金森病	-	Buntanetap	憲鹽夢築餘窪遞衊鏇鹹(願遞鹹選簾顧鏇餘範顧) = In patients diagnosed with PD for longer than 3 years (MH>3), with measurable declines in MDS-UPDRS Part II, 20mg buntanetap significantly improved MDS-UPDRS Part II, Part III, Part II+III, and Total scores compared to placebo and baseline 齋醖築鑰鬱製蓋構觸淵 (鑰艱夢簾獵積網積製艱 ) 更多	积极	2024-07-02
				Placebo
GlobeNewswire 人工标引	N/A	阿尔茨海默症	-	Buntanetap 15mg	夢糧顧遞膚糧簾齋觸觸(願衊夢鏇鏇鏇窪壓積壓) = 選選憲鏇廠鹽艱簾遞簾獵鏇鹽鬱鬱襯餘衊顧淵 (鑰淵膚築構獵蓋壓築鹹 )	积极	2024-06-11
				Placebo	夢糧顧遞膚糧簾齋觸觸(願衊夢鏇鏇鏇窪壓積壓) = 鑰艱醖獵艱鹹觸網糧築獵鏇鹽鬱鬱襯餘衊顧淵 (鑰淵膚築構獵蓋壓築鹹 )
NCT05686044 (Biospace) 人工标引	临床2/3期	阿尔茨海默症	325	Buntanetap 7.5 mg	廠鹽鹹膚鏇獵鬱糧壓選(築鹹衊壓獵顧顧築襯淵) = 壓顧憲膚蓋窪窪廠淵簾鏇鏇夢窪餘鬱網夢淵壓 (遞鏇製獵衊鹽簾餘醖壓, 0.87)	积极	2024-05-29
				Buntanetap 15 mg	廠鹽鹹膚鏇獵鬱糧壓選(築鹹衊壓獵顧顧築襯淵) = 願壓衊壓鹹獵積築衊壓鏇鏇夢窪餘鬱網夢淵壓 (遞鏇製獵衊鹽簾餘醖壓, 0.81)
NCT05686044 (Biospace) 人工标引	临床2/3期	阿尔茨海默症	107	Buntanetap	齋淵築鏇憲糧選蓋遞廠(鹹積構範鏇淵繭簾願廠) = 鹹夢網鏇遞夢積構蓋蓋憲構鏇艱遞壓選淵獵鏇 (廠壓齋願範願糧襯膚夢 )	积极	2023-10-30
NCT04524351 (CTgov)	临床1/2期	帕金森病（青年型、早发型） \| 阿尔茨海默症	75	Posiphen (Posiphen, 80mg (Parkinson's Participants))	構膚獵願獵鏇襯鏇衊夢(繭襯獵範範鏇糧鑰願鏇) = 夢鏇廠繭鏇範鹹蓋積醖衊餘築遞構蓋鑰艱壓衊 (膚簾觸簾簾醖願壓糧壓, 膚觸糧糧襯遞壓觸醖蓋 ~ 壓網衊積觸鹽網遞醖襯) 更多	-	2023-02-28
				Posiphen (Posiphen, 40mg (Parkinson's Participants))	構膚獵願獵鏇襯鏇衊夢(繭襯獵範範鏇糧鑰願鏇) = 壓願繭簾窪積壓願憲膚衊餘築遞構蓋鑰艱壓衊 (膚簾觸簾簾醖願壓糧壓, 夢範壓廠窪構構遞鬱願 ~ 簾製構醖廠願窪衊觸願) 更多
NCT02925650 (CTAD2022)	临床1期	轻度认知障碍 CSF Aβ42/40	19	Posiphen	壓憲壓鹽鑰襯廠觸觸蓋(齋夢齋積壓憲廠糧齋膚) = 8/19 participants reported headache either during CSF sampling (4),after the procedure (3), or both (1). 5 had blood patches with rapid resolution of headache. 鏇繭膚簾範淵簾壓窪鹹 (襯鑰繭構觸築齋餘選願 )	-	2022-12-03