An Open-label, Single-arm Study to Provide Continued Access to Study Drug to Participants Who Have Completed Pediatric Clinical Studies Involving Gilead HIV Treatments

The goal of this clinical study is to provide continued access to the study drug(s) to children and adolescents with human immunodeficiency virus type 1 (HIV-1) who completed their participation in an applicable parent study and to monitor for adverse events.
The primary objectives of this study are as follows:
* To provide continued access to the study drug received in the parent protocol or switch to bictegravir/emtricitabine/tenofovir (B/F/TAF) for participants who completed a Gilead parent study evaluating drugs for HIV treatment.
* To evaluate the safety of the study drug(s) in participants with HIV-1.

开始日期2024-08-27

申办/合作机构

Gilead Sciences, Inc.

NCT04452565

/ Unknown status临床2/3期

Randomized Controlled Phase 2/3 Clinical Trial of NA-831 Alone or With Atazanavir, or NA-831 With Dexamethasone, or Atazanavir With Dexamethasone in the Treatment of COVID-19 Infection

This Phase 2/3 trial evaluates four treatment strategies for non-critically ill hospitalized participants (not requiring ICU admission and/or mechanical ventilation) with SARS CoV-2 infection, in which participants will receive NA-831 or Atazanavir with or without Dexamethasone.

开始日期2022-06-15

申办/合作机构

NeuroActiva, Inc.

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100 项与硫酸阿扎那韦相关的临床结果

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100 项与硫酸阿扎那韦相关的转化医学

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100 项与硫酸阿扎那韦相关的专利（医药）

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4,704

项与硫酸阿扎那韦相关的文献（医药）

2025-04-01·INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

A phase III, randomized, controlled noninferiority trial to study the efficacy and safety of imipenem/cilastatin/relebactam (IMI/REL) vs piperacillin/tazobactam (PIP/TAZ) in patients with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP)

Article

作者: Guo, Xiaodan ; Iamboliyska, Zlatka ; Losada, Maria ; Tang, Zhengang ; Sun, Fang ; Wei, Feng ; Koseoglu, Sandra ; Ding, Lianshu ; Zhu, Mingfen ; Chen, Luke Francis ; Young, Katherine ; Li, Junjie ; Qu, Jieming ; Du, Xiaoling ; Chen, Chang ; Xiang, Peng ; Zhou, Min ; Bruno, Christopher

OBJECTIVES:

Imipenem/cilastatin/relebactam (IMI/REL) is a β-lactam/β-lactamase inhibitor combination effective against gram-negative pathogens. Efficacy and safety of IMI/REL were studied in critically ill adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP).

METHODS:

In this phase III, double-blind, multinational, randomized trial (NCT03583333), adults with HABP/VABP were randomized 1:1 to receive intravenous IMI/REL (500 mg/250 mg) or piperacillin/tazobactam (PIP/TAZ; 4000 mg/500 mg) every 6 h for 7-14 days. The primary endpoint was 28-day all-cause mortality (ACM). Secondary endpoints were clinical response (CR), microbiological response (MR), and adverse event (AE) incidence.

RESULTS:

In the modified intention-to-treat population (N = 270 [IMI/REL: n = 134; PIP/TAZ: n = 136]), demographics and baseline characteristics were comparable between treatment groups. Most patients were from China. IMI/REL was noninferior to PIP/TAZ for 28-day ACM (11.2% vs 5.9%; adjusted difference [95% confidence interval]: 5.2% [-1.5 to 12.4]). Secondary outcomes were comparable between treatment groups, including favorable CR and MR. AEs resulting in death were generally consistent with pre-existing or underlying illness.

CONCLUSIONS:

IMI/REL met noninferiority criteria vs PIP/TAZ for 28-day ACM, and safety profiles were comparable. This trial could support the use of IMI/REL to treat adults with HABP/VABP, including regional use in China.

2025-03-01·JOURNAL OF HAZARDOUS MATERIALS

Potential utilization of bivalve hemolymph as a biomonitoring tool for assessment of atrazine contamination

Article

作者: Nuchan, Pattanan ; Kovitvadhi, Uthaiwan ; Sangsawang, Akkarasiri ; Srakaew, Nopparat ; Kovitvadhi, Satit ; Klaimala, Pakasinee

This study evaluated temporally dynamic bioaccumulation, fates, and biotransformation of atrazine (ATZ) in bivalve hemolymph. Male and female mussels, Hyriopsis bialata, were exposed to ATZ at environmentally-relevant (0.02 and 0.2 mg/L) and high (2 mg/L) concentrations. Untreated mussels served as a control. The hemolymph was collected from the anterior adductor muscle during 28 days of exposure. Pooled hemolymph from individuals of the same sex was subjected to chromatographic analysis of ATZ and its derivatives: desethylatrazine (DEA), desisopropylatrazine (DIA), and hydroxyatrazine (HA). The hemolymph was also used to determine phase I biotransformation via 7-ethoxyresorufin-O-deethylase activity. ATZ-treated mussels showed bioaccumulation of ATZ and its derivatives in their hemolymph, but the control mussels had none. There were no gender-dependent bioaccumulation patterns for these compounds, among which DEA revealed dose- and time-dependent bioaccumulation. Besides, hemolymph-to-water concentration ratios (HWRs) of DEA exhibited concentration and time dependency on nominal ATZ concentrations, especially in the female mussels. ATZ exposure generally did not alter phase I biotransformation capacity in the hemolymph. Interestingly, DEA, aside from ATZ, was a promising candidate marker representing degrees of ATZ contamination. Overall, this study offered opportunity for utilizing the bivalve hemolymph of minimal amounts for rapid, time-series biomonitoring of ATZ contamination in water.

2025-02-01·MARINE ENVIRONMENTAL RESEARCH

Predicted environmental concentration (PEC), environmental risk assessment (ERA) and prioritization of antiretroviral drugs (ARVs) in seawater from Guarujá (Brazilian coastal zone)

Article

作者: Guimarães, Luciana Lopes ; Metropolo, Ana Paula ; Rodrigues, Aírton Zogaib ; de Assis Junior, Wellington Rui Andrade ; Kiyotani, Rafael Barreiros ; Toma, Walber ; Ramos, Leonardo Teixeira ; Dos Santos, Gilmar Aparecido ; Roveri, Vinicius

The antiretroviral therapy program's success in managing the human immunodeficiency virus (HIV) has inadvertently led to the release of antiretrovirals (ARVs) into worldwide aquatic ecosystems. However, few studies investigated the risks of ARV loadings that flow continuously to the marine waters of South America (such as Brazil). Against this backdrop, the aims of this study were: (i) to estimate the Predicted Environmental Concentration (PEC) of thirteen ARVs worldwide used in HIV treatment, and which are frequently disposed of in the marine aquatic ecosystems of Guarujá, São Paulo coastline, Brazil.; (ii) predict, through the Environmental Risk Assessment (ERA), the potential acute and chronic risks of these ARVs; and (iii) create a prioritization list of the most hazardous ARVs, based on the intrinsic properties of these compounds, i.e.: occurrence (O); persistence (P), bioaccumulation (B) and toxicity (T) (OPBT criteria). The PEC calculations indicated that all the ARVs examined in this study require an assessment of their impact on aquatic organisms, as all results exceeded the limits set by the guidelines of the European Medicines Agency., i.e., the PEC ranged between 0.37 and 99.39 μg/L. The results of individual ERA showed the following trend: (i) 56.41% of the results of acute toxicity indicated high toxicity for the three trophic levels; 33.33% of the results indicated low risk for one of the trophic levels, and 10.26% indicated moderate toxicity, and (ii) in terms of chronic toxicity, 33.33% of the results indicated moderate risks, 35.90% indicated low or no risk, and 30.77% indicated high risks. Regarding the results of the mixture of ARVs, the ERA showed a high acute and/or chronic risk for all five classes tested, i.e., (i) nucleoside/nucleotide reverse transcriptase inhibitors; ii) non-nucleoside reverse transcriptase inhibitors; iii) protease inhibitors; (iv) integrase strand transfer inhibitors; and (v) chemokine receptor antagonists. Ultimately, the final ranking of the OPBT approach was etravirine (the highest-priority ARV in seawater from Guarujá), followed by: nevirapine > efavirenz > ritonavir > lopinavir > maraviroc > atazanavir > darunavir > abacavir > dolutegravir > zidovudine > tenofovir > lamivudine.

项与硫酸阿扎那韦相关的新闻（医药）

2024-12-06

·艾美达医药咨询

01 行业新闻丨阿斯利康中国高管团队全面调整 12月4日，阿斯利康中国官网发布消息，阿斯利康任命Iskra Reic为全球执行副总裁、国际业务负责人，全面负责包括中国、亚洲和欧亚市场、中东和非洲、拉丁美洲、澳大利亚和新西兰在内的地区整体战略。此外，阿斯利康中国管理团队多位高管职务发生变动。林骁由阿斯利康中国生物制药业务总经理、呼吸吸入和生物制剂事业部负责人、香港及澳门地区负责人变更为阿斯利康中国总经理，阿斯利康中国生物制药业务总经理；刘谦由阿斯利康中国全渠道事业部总经理变更为阿斯利康中国呼吸消化事业部总经理；关冬梅由阿斯利康中国副总裁-心血管、肾脏及代谢事业部，变更为阿斯利康中国肿瘤业务总经理；谈俊萍由阿斯利康中国副总裁-合规部，变更为阿斯利康中国副总裁-道德和风控部。 02 企业动态丨先声药业脑卒中创新药获批上市 12月2日，先声药业宣布，脑卒中创新药先必新®舌下片（通用名：依达拉奉右莰醇舌下片）于12月1日获国家药品监督管理局批准上市（批准文号：国药准字H20240041），用于改善急性缺血性脑卒中所致的神经症状、日常生活活动能力和功能障碍。临床研究表明，先必新®舌下片能够显著减少急性缺血性卒中导致的脑细胞损伤。2024年8月，先必新®舌下片获美国食品药品监督管理局（FDA）“突破性疗法”认定，是全球脑卒中治疗领域首个获得该认定的创新药，也是中国神经科学领域首个获得该认定的创新药。（先声药业）丨帕金森病治疗新药沙芬酰胺在中国获批 12月2日，中国国家药监局（NMPA）官网公示，由赞邦（Zambon）公司申报的5.1类新药沙芬酰胺片的上市申请已获得批准。公开资料显示，沙芬酰胺（safinamide）是一款用于治疗帕金森病的新化学实体，已经于2017年获得美国FDA批准，针对出现“关闭期”发作的帕金森病患者。根据中国药物临床试验登记与信息公示平台信息，沙芬酰胺作为辅助治疗特发性帕金森病的中国3期临床研究已完成。该研究旨在评价沙芬酰胺作为辅助疗法，用于接受稳定剂量的左旋多巴治疗的、出现运动波动的中国特发性帕金森病患者的疗效。（NMPA、赞邦）丨默沙东抗生素组合新药在中国获批上市 12月2日，NMPA官网最新公示，默沙东（MSD）申报的注射用亚西瑞来新药上市申请已获得批准。公开资料显示，这是一款抗生素组合注射用亚西瑞来（亚胺培南500mg+西司他丁500mg+瑞来巴坦250mg，商品名为Recarbrio）。根据该产品在中国的临床研究进度推测，该药本次获批的适应症可能为治疗医院获得性细菌性肺炎和呼吸机相关细菌性肺炎（HABP/VABP）。在中国，根据药物临床试验登记与信息公示平台，默沙东已经完成了一项国际多中心（含中国）3期、随机、双盲临床试验，在HABP/VABP受试者中比较亚西瑞来和哌拉西林+他唑巴坦（PIP/TAZ）的安全性、耐受性和疗效。（默沙东）丨银诺医药在港交所递交IPO申请 12月3日，港交所官网公示，银诺医药已经在港交所递交了IPO申请。银诺医药成立于2014年，致力于研发治疗糖尿病和其他代谢性疾病的创新疗法。该公司的长效GLP-1受体激动剂依苏帕格鲁肽α有望即将进入商业化阶段，用于治疗2型糖尿病的单药疗法及与二甲双胍的联合用药均已在中国递交上市申请。除了依苏帕格鲁肽α，银诺医药还有5款处于IND待启动阶段的候选药物。银诺医药的核心产品依苏帕格鲁肽α是该公司自主研发的人源长效GLP-1受体激动剂，旨在用于治疗2型糖尿病（T2D）和其他代谢性疾病。（银诺医药）丨锦篮基因GC101腺相关病毒注射液拟纳入突破性治疗品种 12月3日，国家药品监督管理局药品审评中心（CDE）官网消息显示，锦篮基因申报的GC101腺相关病毒注射液拟纳入突破性治疗品种，用于治疗2型脊髓性肌萎缩症（5q SMA）。根据锦篮基因公开资料介绍，GC101腺相关病毒注射液一种携带正常SMN1基因表达单元的重组9型腺相关病毒载体（rAAV9），通过鞘内注射方式一次性给药，使SMN1基因在运动神经元细胞表达，从而改善运动神经元等受累细胞的功能，辅以呼吸及运动康复训练，可以改善提高SMA患者呼吸能力及运动能力。（CDE、锦篮基因）丨杰科生物JL15003注射液拟纳入突破性治疗品种 12月3日，CDE官网消息显示，杰科生物申报的JL15003注射液拟纳入突破性治疗品种，用于治疗复发胶质母细胞瘤。根据杰科生物公开资料，JL15003为溶瘤病毒产品，也是公司首个获批临床的1类新药。该产品目前正处于1期临床研究阶段，评价其治疗复发胶质母细胞瘤患者的安全性和耐受性。利用自然界中致病力较弱的病毒进行基因工程改造，让它们失去毒性并保留病毒的复制能力，再将溶瘤病毒注射入肿瘤病灶内，使其在肿瘤细胞内自我复制，随后裂解肿瘤细胞，这就是溶瘤病毒免疫疗法。（CDE，杰科生物）丨映恩生物创新临床前ADC药物授权GSK 12月4日，映恩生物宣布与葛兰素史克（GSK）已就一项抗体偶联药物（ADC）DB-1324达成独家授权协议。根据协议，GSK将获得全球（不包括中国大陆、香港地区和澳门地区）的独家授权，以推进该ADC药物的研发与商业化进程。根据协议条款，GSK将预先支付3000万美元预付款及其他行权前里程碑付款以获得在全球范围内（中国大陆、香港地区和澳门地区除外）推进DB-1324研发和商业化的独家授权许可。如果GSK行使许可权，映恩生物将收取行权费以及后续在开发、法规注册和商业化不同阶段的里程碑付款，最高可达9.75亿美元。（映恩生物）丨恒瑞医药ADC新药拟纳入突破性治疗品种 12月4日，CDE官网公示，恒瑞医药1类新药注射用SHR-A2102拟纳入突破性治疗品种，适应症为单药治疗既往含铂化疗和PD-(L)1抑制剂治疗失败的局部晚期或转移性尿路上皮癌。SHR-A2102是恒瑞医药自主研发的靶向Nectin-4的抗体偶联药物（ADC）。该药治疗晚期尿路上皮癌此前已经被美国FDA授予快速通道资格。SHR-A2102为一款靶向Nectin-4的ADC，其有效载荷是拓扑异构酶抑制剂（TOPi）。此前，该产品用于治疗晚期实体瘤的临床试验申请已获得FDA许可。（恒瑞医药）丨和黄医药赛沃替尼肺癌联合疗法拟纳入突破性治疗品种 12月4日，CDE官网最新公示，和黄医药申报的1类新药赛沃替尼片拟纳入突破性治疗品种，适应症为赛沃替尼联合奥希替尼治疗经EGFR-TKI治疗失败伴MET扩增的局部晚期或转移性非小细胞肺癌。公开资料显示，奥希替尼是一种不可逆的第三代EGFR-TKI；赛沃替尼片是一种强效、高选择性的口服间充质上皮转化因子 (MET) TKI。赛沃替尼是一种强效、高选择性的口服MET TKI，由阿斯利康（AstraZeneca）与和黄医药联合开发，并由阿斯利康负责商业化。（和黄医药）丨阿斯利康“ADC+双抗”联合疗法在中国获批临床 12月5日，CDE官网最新公示显示，由阿斯利康（AstraZeneca）申报的AZD2936和DS-8201a两款新药同时获得临床试验默示许可，适应症为局部晚期或转移性HER2表达胆道癌患者的一线治疗。DS-8201a（即注射用德曲妥珠单抗，Enhertu）是阿斯利康和第一三共联合开发的靶向HER2的抗体偶联药物（ADC）；AZD2936（rilvegostomig）是一款靶向PD-1/TIGIT的双特异性抗体。阿斯利康正在全球范围内开展3期临床研究（DESTINY-BTC01），探索Enhertu + rilvegostomig联合疗法一线治疗HER2阳性胆道癌。这也正是该联合疗法在中国获批临床的适应症。（阿斯利康）丨再鼎医药银屑病1类新药首次在中国获批临床 12月5日，CDE官网公示，再鼎医药申报的1类新药ZL-1102凝胶获得临床试验默示许可，拟开发用于局部治疗慢性斑块状银屑病。根据再鼎医药公开资料，ZL-1102是一款靶向作用于IL-17A细胞因子的新型全人源VH抗体片段（Humabody），为该公司内部开发的新药。与其他针对中重度慢性斑块状银屑病的全身型IL-17抑制剂不同，ZL-1102的独特之处在于被开发用于治疗轻中度慢性斑块状银屑病。目前ZL-1102凝胶已经在澳大利亚内启动2期临床研究。（再鼎医药）丨辉瑞泛KRAS抑制剂癌症新药首次在中国申报临床 12月5日，CDE官网公示，辉瑞1类新药PF-07934040片临床试验申请获得受理。公开资料显示，这是辉瑞公司在研的一款泛KRAS抑制剂，正在国际范围内开展1期临床。本次是该产品首次在中国申报IND。KRAS是最早发现的癌症基因之一，其突变在癌症患者中很常见。在发现KRAS G12C抑制剂之后，目前科学家们已经将目标转向其它KRAS突变体，旨在开发出能够靶向多种、甚至全部KRAS突变体的泛KRAS（pan-KRAS）靶向疗法，为携带KRAS突变的诸多癌症类型提供治疗选择。（辉瑞）丨宜明昂科公布双抗癌症新药1期临床结果 12月6日，宜明昂科宣布，阿沐瑞芙普α（IMM0306）针对淋巴瘤临床1期试验数据全文被Journal of Hematology & Oncology期刊接受。阿沐瑞芙普α是一款CD47xCD20双靶点特异性分子。数据显示，在25例疗效可评估的R/R滤泡性淋巴瘤（FL）患者中，总体缓解率(ORR)和完全缓解率(CRR)分别是84.0%和40.0%；2例疗效可评估的R/R边缘区淋巴瘤（MZL）患者ORR为100%。（宜明昂科） *声明：本文不构成任何投资建议，仅出于传递更多信息之目的。 ------------------------------ 「长按」二维码添加小达「进群」与更多行业伙伴共探市场前沿资讯艾美达医药咨询艾美达（北京）医药信息咨询有限公司，成立于2014年4月，是一家专业的医药行业咨询服务提供商。公司致力于将产业政策研究与真实世界的数据挖掘深度结合，洞悉行业政策对市场的影响，通过专业的研究提供前瞻性的市场分析，为企业产品上市后的市场准入提供整体解决方案。

突破性疗法高管变更上市批准

2024-12-02

·医药观澜

默沙东抗生素组合新药在中国获批上市

▎药明康德内容团队报道今日（12月2日），中国国家药监局（NMPA）官网最新公示，默沙东（MSD）申报的注射用亚西瑞来新药上市申请已获得批准。公开资料显示，这是一款抗生素组合注射用亚西瑞来（亚胺培南500mg+西司他丁500mg+瑞来巴坦250mg，商品名为Recarbrio）。根据该产品在中国的临床研究进度推测，该药本次获批的适应症可能为治疗医院获得性细菌性肺炎和呼吸机相关细菌性肺炎（HABP/VABP）。截图来源：NMPA官网亚西瑞来是亚胺培南、西司他丁和瑞来巴坦的复方制剂。其中，亚胺培南是一款获批β-内酰胺类抗生素，西司他丁可防止亚胺培南被肾脏分解，瑞来巴坦是一种二氮杂双环辛烷β-内酰胺酶抑制剂，具有广谱抗β-内酰胺酶活性。虽然β-内酰胺酶抑制剂本身没有抗生素活性，但它可以增强β-内酰胺类抗生素的活性。 2019年7月，亚西瑞来首次在美国获批上市，商品名为Recarbrio，治疗由特定敏感革兰氏阴性菌导致的复杂性尿路感染（cUTI）和复杂性腹腔内感染（cIAI）。2020年6月，亚西瑞来获美国FDA批准扩展适应症，治疗18岁以上的HABP/VABP患者。该产品曾经获得FDA授予的合格传染病产品（QIDP），快速通道和优先审评资格。在中国，根据药物临床试验登记与信息公示平台，默沙东已经完成了一项国际多中心（含中国）3期、随机、双盲临床试验，在HABP/VABP受试者中比较亚西瑞来和哌拉西林+他唑巴坦（PIP/TAZ）的安全性、耐受性和疗效。 Recarbrio在美国获批治疗HABP/VABP是基于一项关键的3期RESTORE-IMI 2试验的结果。在这项试验中，264名患者接受Recarbrio的治疗，267名患者接受哌拉西林+他唑巴坦（PIP/TAZ）治疗。该研究达到了主要和关键次要终点。在接受治疗28天内，15.9%接受Recarbrio治疗的患者死亡，接受哌拉西林+他唑巴坦治疗的患者死亡率为21.3%。 HABP/VABP是肺炎的一种，多发生于住院患者，可引起发热、寒战、咳嗽、胸痛和需氧量增加等症状。由于抗生素的过多使用，很多导致HABP和VABP的细菌对已有抗生素产生耐药性。因此患者需要新的抗生素来控制细菌感染。期待亚西瑞来此次在中国的获批能够尽快让中国的严重细菌感染患者获得安全有效的新疗法。参考资料： [1] 2024年12月02日药品批准证明文件送达信息. From https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20241202104249182.html [2] FDA Approves Merck’s RECARBRIO™ (imipenem, cilastatin, and relebactam) for the Treatment of Adults with Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP). Retrieved Jun 5, 2024, from https://www.businesswire.com/news/home/20200605005187/en/ [3] 药物临床试验登记与信息公示平台. From http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

优先审批临床3期快速通道临床结果合格传染病产品

2024-11-06

·GlobeNewswire-Health Care

Denali Therapeutics Reports Third Quarter 2024 Financial Results and Business Highlights

SOUTH SAN FRANCISCO, Calif., Nov. 06, 2024 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the third quarter ended September 30, 2024, and provided business highlights. "As leaders in pioneering a new class of therapeutics that cross the blood-brain barrier, we are making significant progress across our Transport Vehicle (TV)-enabled portfolio,” said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics. “Within our Enzyme TV (ETV) franchise, we are on track to file for accelerated approval of tividenofusp alfa in MPS II in early 2025 after a successful meeting with the FDA in the third quarter. Today, we are also pleased to share that preliminary data from our Phase 1/2 study of DNL126 in MPS IIIA demonstrate a robust reduction from baseline in CSF heparan sulfate levels, including normalization. Based on these data and a positive regulatory environment, we recently expanded the study to support a potential accelerated path. In addition, our recent preclinical publication on our oligonucleotide TV (OTV) technology in Science Translational Medicine, which describes broad and deep brain biodistribution of oligonucleotides following systemic administration of OTV, demonstrates the power and potential of our TV platform to transform the way we treat brain diseases.” Third Quarter 2024 and Recent Program Updates Late-stage and mid-stage clinical programs Tividenofusp alfa (DNL310): Enzyme Transport Vehicle (ETV)-enabled, iduronate-2-sulfatase (IDS) replacement therapy in development for MPS II (Hunter syndrome) In September, announced the outcome of a successful meeting with the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA) providing a path to filing a biologics license application (BLA) for accelerated approval and subsequent conversion to full approval for tividenofusp alfa (DNL310) for the treatment of MPS II. Agreement was reached that cerebrospinal fluid heparan sulfate (CSF HS) is reasonably likely to predict clinical benefit and can be used as a surrogate endpoint to support accelerated approval for tividenofusp alfa in MPS II. Denali intends to submit the BLA under the accelerated approval pathway in early 2025.In September, presented new interim data from the Phase 1/2 study at the Society for the Study of Inborn Errors of Metabolism (SSIEM 2024), including data from additional study participants (N=37) and longer duration of treatment with tividenofusp alfa (up to Week 129) as well as new analyses on biomarkers and clinical outcomes.COMPASS, the global Phase 2/3 study, is expected to complete enrollment in 2024. DNL343: eIF2B activator in development for the treatment of amyotrophic lateral sclerosis (ALS) DNL343 is being evaluated in Regimen G (DNL343) of the Phase 2/3 HEALEY ALS Platform Trial conducted by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) in collaboration with the Northeast ALS Consortium (NEALS). Enrollment in Regimen G is complete. SAR443820/DNL788: CNS-penetrant RIPK1 inhibitor In October, Denali was informed by its strategic partner Sanofi that the K2 Phase 2 study evaluating the safety and efficacy of oditrasertib (SAR443820/DNL788) on serum neurofilament light chain levels in participants with multiple sclerosis was discontinued based on not meeting the primary and key secondary endpoints. BIIB122/DNL151: LRRK2 inhibitor in development for the treatment of Parkinson’s disease (PD) Biogen is conducting the ongoing global Phase 2b LUMA study of BIIB122 in participants with early-stage Parkinson’s disease.Denali has initiated screening of participants for the global Phase 2a study to evaluate safety and biomarkers associated with BIIB122 in participants with Parkinson’s disease and confirmed pathogenic variants of LRRK2. This study is being funded under the Collaboration and Development Funding Agreement with a third party. Eclitasertib (SAR443122/DNL758): Peripheral RIPK1 inhibitor in development for the treatment of ulcerative colitis (UC) Sanofi is conducting the ongoing Phase 2 study of SAR443122/DNL758 in participants with UC. Early-stage clinical and preclinical programs DNL126: ETV-enabled N-sulfoglucosamine sulfohydrolase (SGSH) replacement therapy in development for the treatment of MPS IIIA (Sanfilippo syndrome Type A) Denali today announced that preliminary data from up to 25 weeks of dosing in the ongoing open-label Phase 1/2 study in MPS IIIA participants demonstrate a significant reduction in CSF HS levels from baseline, including normalization. The safety profile supports continued development. The most frequent treatment emergent adverse events were infusion related reactions of mild and moderate severity in all participants. There was one serious adverse event considered by the investigator not related to drug. Denali plans to present the data at a future medical meeting.Based on the preliminary Phase 1/2 results and a positive regulatory environment, Denali recently expanded the study and continues to assess the development plans including an accelerated approval path.DNL126 was selected in June 2024 for the FDA's Support for clinical Trials Advancing Rare disease Therapeutics (START) program to accelerate the development of rare disease therapeutics, and collaborative engagement has commenced to support progress to a pre-BLA meeting. TAK-594/DNL593: Protein Transport Vehicle (PTV)-enabled progranulin (PGRN) replacement therapy in development for the treatment of frontotemporal dementia-granulin (FTD-GRN) Screening of participants for Cohort B2 in the Phase 1/2 study is ongoing. Oligonucleotide Transport Vehicle (OTV) platform Denali is advancing OTV:MAPT, targeting tau for Alzheimer’s disease, and OTV:SNCA, targeting alpha-synuclein for Parkinson’s disease, in the investigational new drug (IND)-enabling stage of development.In August, announced publication of nonclinical data in the August 14, 2024 issue of Science Translational Medicine (link) demonstrating the ability of the OTV platform to achieve broad biodistribution of antisense oligonucleotides (ASOs) in the central nervous system and skeletal and cardiac muscle following intravenous administration. Antibody Transport Vehicle Amyloid beta (ATV:Abeta) program Denali is working to develop the next generation of anti-amyloid beta therapeutics with ATV:Abeta, which is designed to increase exposure of the therapeutic antibody and achieve broad biodistribution in the brain with the potential for improved efficacy and safety. Preclinical data demonstrated potential for a wider therapeutic window compared to a standard antibody, with superior plaque decoration and reduction and very low rates of amyloid related imaging abnormalities (ARIA). These data are included in a manuscript posted on bioRxiv (link).Denali plans to advance a TfR-targeting ATV:Abeta molecule as well as a CD98hc-targeting ATV:Abeta molecule into development for Alzheimer's disease. Discovery programs Denali applies its deep scientific expertise in neurodegeneration biology and the BBB to discover and develop medicines and platforms with the focus on programs enabled by the TV technology and targeting neurodegenerative disease, including Alzheimer’s and Parkinson’s, and lysosomal storage diseases. 2024 Guidance on Operating Expenses Cash, cash equivalents, and marketable securities were approximately $1.28 billion as of September 30, 2024. Denali is providing updated guidance on cash operating expenses for the full year 2024 and now anticipates an increase of approximately 5-10% compared to 2023, which is an increase from previous guidance of equal to or less than full year 2023 cash operating expenses. This updated guidance is associated with increased activities to support filing of a BLA in early 2025 and commercial readiness for tividenofusp alfa in MPS II, and to accelerate the development of additional therapeutic programs in Denali's TV platform portfolio. Participation in Upcoming Investor Conferences UBS Global Healthcare Conference, November 11-14B. Riley Securities’ Next-Gen Tissue Delivery Modalities Virtual Summit, November 14Stifel 2024 Healthcare Conference, November 18-19Jefferies London Healthcare Conference, November 19-217th Annual Evercore ISI HealthCONx Conference, December 3-5 Third Quarter 2024 Financial Results Net losses were $107.2 million and $99.4 million for the three months ended September 30, 2024 and 2023, respectively. There was no collaboration revenue for the quarter ended September 30, 2024, compared to $1.3 million for the quarter ended September 30, 2023. The decrease in collaboration revenue was primarily due to activities under the Biogen Collaboration Agreement. Total research and development expenses were $98.2 million for the quarter ended September 30, 2024, compared to $89.7 million for the quarter ended September 30, 2023. The increase of approximately $8.5 million for the quarter ended September 30, 2024 was primarily attributable to increases in costs in various clinical stage programs, including ETV:IDS, eIF2B, ETV:SGSH, and LRRK2 reflecting the continued progress of these programs in clinical trials, and increases in TV platform and other program external expenses, reflecting continued investment in TV-enabled product candidates. These increases were partially offset by a decrease in personnel and external expenses associated with the divestiture of Denali’s preclinical small molecule programs. General and administrative expenses were $24.9 million for the quarter ended September 30, 2024, and $25.3 million for the same period in 2023. About Denali Therapeutics Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB, and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding expectations regarding Denali’s TV technology platform; statements made by Denali’s Chief Executive Officer; plans, timelines, and expectations regarding DNL310 and the ongoing Phase 2/3 COMPASS and Phase 1/2 studies, the timing and likelihood of accelerated approval, and the timing and availability of program updates; plans and timelines regarding DNL343, including the timing and availability of data from the Phase 2/3 HEALEY ALS Platform Trial; plans, timelines, and expectations of both Denali and Sanofi regarding DNL788; plans, timelines, and expectations regarding DNL151, including with respect to the ongoing LUMA study as well as enrollment and timing of the proposed Phase 2a study in PD patients with LRRK2 mutations; expectations regarding DNL758, including the ongoing Phase 2 study in patients with UC; plans, timelines, and expectations related to DNL126, including the timing and availability of data in the ongoing Phase 1/2 study and the timing and likelihood of regulatory approval; plans, timelines, and expectations of both Denali and Takeda regarding DNL593 and the ongoing Phase 1/2 study; plans, timelines, and expectations regarding the advancement of OTV:MAPT and OTV:SNCA towards clinical development; plans, timelines, and expectations regarding the ATV:Abeta program, including its therapeutic potential and the clinical advancement of ATV:Abeta molecules; plans and expectations for Denali's preclinical programs; Denali's future operating expenses and anticipated cash runway; and Denali's participation in upcoming investor conferences. All drugs currently being developed by Denali are investigational and have not received regulatory approval for any indication. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: any and all risks to Denali’s business and operations caused by adverse economic conditions; risk of the occurrence of any event, change, or other circumstance that could give rise to the termination of Denali’s agreements with Sanofi, Takeda, or Biogen, or any of Denali’s other collaboration agreements; Denali’s transition to a late-stage clinical drug development company; Denali’s and its collaborators’ ability to complete the development and, if approved, commercialization of its product candidates; Denali’s and its collaborators’ ability to enroll patients in its ongoing and future clinical trials; Denali’s reliance on third parties for the manufacture and supply of its product candidates for clinical trials; Denali’s dependence on successful development of its blood-brain barrier platform technology and its programs and product candidates; Denali’s and its collaborators' ability to conduct or complete clinical trials on expected timelines; the risk that preclinical profiles of Denali’s product candidates may not translate in clinical trials; the potential for clinical trials to differ from preclinical, early clinical, preliminary or expected results; the risk of significant adverse events, toxicities or other undesirable side effects; the uncertainty that product candidates will receive regulatory approval necessary to be commercialized; Denali’s ability to continue to create a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali’s strategic plans for its business, product candidates, and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 28, 2024 and August 1, 2024, respectively, and Denali’s future reports to be filed with the SEC. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results, or to make changes in Denali’s expectations, except as required by law. Denali Therapeutics Inc.Condensed Consolidated Statements of Operations(Unaudited)(In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Collaboration revenue: Collaboration revenue from customers(1)$— $1,267 $— $330,531 Other collaboration revenue — — — — Total collaboration revenue — 1,267 — 330,531 Operating expenses: Research and development(2) 98,238 89,737 296,653 316,073 General and administrative 24,949 25,325 75,379 78,585 Total operating expenses 123,187 115,062 372,032 394,658 Gain from divestiture of small molecule programs — — 14,537 — Loss from operations (123,187) (113,795) (357,495) (64,127)Interest and other income, net 15,995 14,442 49,475 38,376 Net loss$(107,192) $(99,353) $(308,020) $(25,751)Net loss per share, basic and diluted$(0.63) $(0.72) $(1.89) $(0.19)Weighted average number of shares outstanding, basic and diluted 169,456,988 137,644,534 162,589,325 137,076,199 __________________________________________________ (1) Includes related-party collaboration revenue from customers of $1.3 million and $295.5 million for the three and nine months ended September 30, 2023, respectively.(2) Includes expenses for cost sharing payments due to a related party of $3.4 million and $14.5 million for the three and nine months ended September 30, 2023, respectively. Denali Therapeutics Inc.Condensed Consolidated Balance Sheets(Unaudited)(In thousands) September 30, 2024 December 31, 2023Assets Current assets: Cash and cash equivalents$90,636 $127,106Short-term marketable securities 745,923 907,405Prepaid expenses and other current assets 32,280 29,626Total current assets 868,839 1,064,137Long-term marketable securities 445,463 —Property and equipment, net 50,822 45,589Operating lease right-of-use asset 23,717 26,048Finance lease right-of-use asset 38,685 —Other non-current assets 26,487 18,143Total assets$1,454,013 $1,153,917Liabilities and stockholders' equity Current liabilities: Accounts payable$9,594 $9,483Accrued clinical and other research & development costs 23,923 19,035Accrued manufacturing costs 9,568 15,462Accrued compensation 14,874 21,590Operating lease liability, current 8,036 7,260Deferred research and development funding liability, current 16,269 —Other accrued costs and current liabilities 4,829 5,152Total current liabilities 87,093 77,982Operating lease liability, less current portion 38,850 44,981Finance lease liability, less current portion 5,631 —Deferred research funding and development liability, less current portion 3,944 —Total liabilities 135,518 122,963Total stockholders' equity 1,318,495 1,030,954Total liabilities and stockholders’ equity$1,454,013 $1,153,917 Investor Contact:Laura Hansen, Ph.D.Vice President, Investor Relationshansen@dnli.com(650) 452-2747 Media Contact:Rich AllanFGS Global Rich.Allan@fgsglobal.com(503) 851-0807

临床2期财报加速审批

100 项与硫酸阿扎那韦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01276	硫酸阿扎那韦	J05AE08	DB01072

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
HIV感染	美国	Bristol Myers Squibb Co.	2003-06-20

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
高脂血症	临床3期	美国	Bristol Myers Squibb Co.	2004-01-01
病毒血症	临床3期	美国	Bristol Myers Squibb Co.	2004-01-01

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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


NCT01620944 (CTgov)	临床3期	HIV感染	3	RTVHS+Tenofovir+Atazanavir+FTC+TDF+ritonavir (Arm A)	簾構鬱範壓鏇襯餘壓鏇(選淵夢憲簾繭積廠壓艱) = 廠膚膚夢繭鹽衊築餘選餘窪構壓簾憲鬱鑰鏇獵 (鹽夢顧淵鹽遞鬱選簾範, 窪願醖糧遞廠夢觸積夢 ~ 網夢築繭構選衊觸繭網) 更多	-	2021-08-06
				RTVHS+ATV+ritonavir (Arm B)	簾構鬱範壓鏇襯餘壓鏇(選淵夢憲簾繭積廠壓艱) = 範糧醖鹹壓餘願鑰衊廠餘窪構壓簾憲鬱鑰鏇獵 (鹽夢顧淵鹽遞鬱選簾範, 簾鏇夢鏇鑰蓋獵襯襯鹽 ~ 鹹憲觸醖積糧膚艱簾餘) 更多
NCT00940771 (CTgov)	临床4期	HIV感染	10	Boosted Atazanavir	顧繭構膚觸鏇憲壓網齋(夢夢築鹹觸糧獵築窪鬱) = 憲鑰艱構鑰窪憲願鏇範繭範鑰蓋艱醖夢淵鑰製 (餘壓膚衊窪壓簾窪夢糧, 淵製製壓鏇願願窪窪遞 ~ 餘夢蓋壓鹹積範鬱醖鏇) 更多	-	2020-04-20
NCT01388543 (CTgov)	临床4期	HIV感染	31	Atazanavir (CYP3A5 Expressors)	鹽觸蓋壓獵範膚窪蓋範(餘鑰獵鬱淵鹹鏇艱窪鹽) = 淵觸繭餘顧淵鏇醖齋網製壓繭壓鏇獵醖積憲範 (鏇鹽醖獵遞網夢淵願鏇, 壓衊糧鹽夢願網鏇糧鏇 ~ 製艱獵繭廠廠蓋構餘製)	-	2019-11-19
				Atazanavir (CYP3A5 Non-expressors)	鹽觸蓋壓獵範膚窪蓋範(餘鑰獵鬱淵鹹鏇艱窪鹽) = 齋鹽衊齋齋憲顧壓築蓋製壓繭壓鏇獵醖積憲範 (鏇鹽醖獵遞網夢淵願鏇, 齋餘憲鏇網膚夢淵淵窪 ~ 壓醖膚淵壓網夢鏇齋憲) 更多
ASN2019	N/A	间质性肾炎 HIV infection	-	Atazanavir (ATZV)	襯積構窪範遞齋觸壓窪(積淵鏇衊齋顧繭繭製鑰) = A kidney biopsy was performed and the specimen showed: interstitial mononuclear infiltrate with numerous eosinophils, a granulomatous process with central necrosis, crystal-like material and neutrophils, moderate interstitial fibrosis, and 9/15 obsolescent glomeruli 蓋膚襯鹽鑰壓簾襯觸鑰 (鏇鹹觸壓夢鏇觸遞鏇蓋 )	-	2019-11-05
				Prednisone
NCT01351740 (SUAT, CTgov)	临床4期	HIV感染	50	atazanavir (Switch)	齋顧衊獵鑰壓顧夢獵鏇(襯壓糧壓構淵鏇遞夢廠) = 繭獵糧遞鬱淵鏇積遞鏇顧獵範遞製築襯觸艱網 (顧積顧選夢簾願製鹽憲, 鹽艱選廠餘窪繭鏇齋範 ~ 選醖鏇遞觸糧構齋醖膚) 更多	-	2018-07-30
				atazanavir/ritonavir (Continuation)	齋顧衊獵鑰壓顧夢獵鏇(襯壓糧壓構淵鏇遞夢廠) = 鹽鬱齋衊壓襯襯構齋齋顧獵範遞製築襯觸艱網 (顧積顧選夢簾願製鹽憲, 製鏇廠顧積鹽膚夢襯積 ~ 願艱壓淵積製積網獵襯) 更多
NCT02246998 (CTgov)	临床4期	HIV感染	72	STB+iohexol (STB + Iohexol)	觸鏇膚鹹糧窪範窪衊構(淵壓鏇願醖遞淵鑰淵糧) = 壓窪鏇廠醖範觸齋積構襯窪鹽積醖積蓋遞鬱範 (窪選窪壓鹽窪糧鑰網願, 淵憲簾願願襯糧廠衊糧 ~ 觸窪繭遞衊顧製衊壓襯) 更多	-	2018-01-03
				ATV+iohexol+TVD+RTV (TVD + ATV/r + Iohexol)	觸鏇膚鹹糧窪範窪衊構(淵壓鏇願醖遞淵鑰淵糧) = 餘遞膚夢醖築淵獵構觸襯窪鹽積醖積蓋遞鬱範 (窪選窪壓鹽窪糧鑰網願, 鑰醖壓糧艱顧窪艱網繭 ~ 鹽積齋醖夢襯繭繭顧窪) 更多
FHDH-ANRS-CO4 (IAS2018)	N/A	HIV感染	-	Atazanavir	餘遞鹽鹹齋鑰願獵壓壓(選夢醖顧簾鑰膚廠糧醖) = 憲鬱積簾願膚憲艱網範顧醖鏇衊壓淵獵顧膚鬱 (襯遞艱憲遞襯築觸淵糧 ) 更多	-	2018-01-01
				Darunavir	餘遞鹽鹹齋鑰願獵壓壓(選夢醖顧簾鑰膚廠糧醖) = 鑰衊齋鑰範膚選顧糧簾顧醖鏇衊壓淵獵顧膚鬱 (襯遞艱憲遞襯築觸淵糧 ) 更多
NCT01003990 (CTgov)	临床3期	HIV感染	710	Atazanavir (ATV) (Atazanavir (ATV))	積繭淵醖獵簾餘範鬱顧(餘鏇鹹蓋網積憲膚遞積) = 糧構選網壓窪憲鬱網簾窪鏇遞鏇選遞齋獵醖糧 (製觸齋齋顧鹽襯衊醖齋, 獵淵衊顧繭遞膚齋遞築 ~ 鹽繭鏇遞遞廠鏇繭憲糧) 更多	-	2017-05-11
				ATV+Ritonavir (Atazanavir/Ritonavir (ATV/RTV))	積繭淵醖獵簾餘範鬱顧(餘鏇鹹蓋網積憲膚遞積) = 網糧廠憲網壓廠淵齋顧窪鏇遞鏇選遞齋獵醖糧 (製觸齋齋顧鹽襯衊醖齋, 鑰齋窪壓襯醖衊膚製遞 ~ 顧艱衊壓選壓淵糧襯顧) 更多
NCT03019783 (CTgov)	临床2/3期	HIV感染	60	Placebo (Remains on Baseline HIV Regimen)	衊製窪襯選窪構膚鑰鹹(鬱窪淵範廠窪範選蓋願) = 餘構願鑰鹽顧製積壓夢襯窪築選窪繭廠壓壓淵 (餘齋鏇蓋遞餘醖鹹鬱觸, 艱鹽選觸構襯鹹築蓋顧 ~ 壓遞衊簾觸簾淵選獵鹹) 更多	-	2017-04-18
				Atazanavir (Atazanavir Switch)	衊製窪襯選窪構膚鑰鹹(鬱窪淵範廠窪範選蓋願) = 憲夢鑰製糧遞範鏇遞膚襯窪築選窪繭廠壓壓淵 (餘齋鏇蓋遞餘醖鹹鬱觸, 膚網廠顧遞壓簾築網繭 ~ 廠鑰構蓋築選構憲築鏇) 更多
NCT01351740 (Pubmed \| HIV Clin Trials)	临床4期	HIV感染	50	ATV/r 300/100 mg daily	範簾獵蓋夢齋齋醖範範(築築襯範廠廠簾顧夢廠) = 構醖窪網簾鹹製憲鑰鏇衊憲鹽膚齋淵餘鬱窪窪 (餘遞艱衊鬱繭願淵艱觸 )	-	2017-01-01
				ATV 400 mg daily	範簾獵蓋夢齋齋醖範範(築築襯範廠廠簾顧夢廠) = 蓋顧選糧顧繭構窪選醖衊憲鹽膚齋淵餘鬱窪窪 (餘遞艱衊鬱繭願淵艱觸 )