Open-label, Non-randomised, One-sequence Crossover Study to Investigate the Effect of Inhibition of CYP3A4/5 by Erythromycin on the Pharmacokinetics of CHF6001 in Healthy Subjects

The objective of this study is to investigate the effect of the interaction of Erythromycin (CYP3A4/5 moderate inhibitor) on the pharmacokinetic of CHF6001 (CYP3A4/5 substrate) in Healthy Volunteers.

开始日期2024-03-28

申办/合作机构

CHIESI Farmaceutici SpA

NCT06029595

/ Recruiting临床2期

A 52-week, Randomised, Double Blind, Multicentre, 2-arm Parallel Group Trial Assessing Efficacy of CHF6001 (Total Daily Dose 3200μg) Dry Powder Inhaler (DPI) add-on to Maintenance Medium or High Dose of Inhaled Corticosteroids in Combination With Long-acting ß2-agonists in Subjects With Uncontrolled Asthma

The purpose of this study is to evaluate the efficacy and safety of CHF6001 (Tanimilast) as add-on to maintenance of inhaled corticosteroids in combination with Long-acting ß2-agonists in the target patient population. (TANGO)

开始日期2023-11-26

申办/合作机构

CHIESI Farmaceutici SpA

100 项与 Tanimilast 相关的临床结果

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100 项与 Tanimilast 相关的转化医学

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100 项与 Tanimilast 相关的专利（医药）

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项与 Tanimilast 相关的文献（医药）

2023-09-01·American journal of respiratory and critical care medicine

Serum IL-8 as a Determinant of Response to Phosphodiesterase-4 Inhibition in Chronic Obstructive Pulmonary Disease

Article

作者: Bassi, Michele ; Govoni, Mirco ; Santoro, Debora ; Singh, Dave ; Donegan, Sinéad

Rationale: Phosphodiesterase-4 (PDE4) inhibitors have demonstrated increased efficacy in patients with chronic obstructive pulmonary disease who had chronic bronchitis or higher blood eosinophil counts. Further characterization of patients who are most likely to benefit is warranted. Objective: To identify determinants of response to the PDE4 inhibitor tanimilast. Methods: A PDE4 gene expression signature in blood was developed by unsupervised clustering of the ECLIPSE study dataset (ClinicalTrials.gov ID: NCT00292552; Gene Expression Omnibus Series ID: GSE76705). The signature was further evaluated using blood and sputum transcriptome data from the BIOMARKER study (NCT03004417; GSE133513), enabling validation of the association between PDE4 signaling and target biomarkers. Predictivity of the associated biomarkers against clinical response was then tested in the phase-2b PIONEER tanimilast study (NCT02986321). Measurements and Main Results: The PDE4 gene expression signature developed in the ECLIPSE dataset classified subgroups of patients associated with different PDE4 signaling in the BIOMARKER cohort with an area under the receiver operator curve of 98%. In the BIOMARKER study, serum IL-8 was the only variable that was consistently associated with PDE4 signaling, with lower levels associated with higher PDE4 activity. In the PIONEER study, the exacerbation rate reduction mediated by tanimilast treatment increased up to twofold in patients with lower IL-8 levels; 36% versus 18%, reaching statistical significance at ⩽20 pg/ml (P = 0.035). The combination with blood eosinophils ⩾150 μl^-1 or chronic bronchitis provided further additive exacerbation rate reduction: 45% (P = 0.013) and 47% (P = 0.027), respectively. Conclusions: Using selected heterogeneous datasets, this analysis identifies IL-8 as an independent predictor of PDE4 inhibition, as tanimilast had a greater effect on exacerbation prevention in patients with chronic obstructive pulmonary disease who had lower baseline serum IL-8 levels. Testing of this biomarker in other datasets is warranted. Clinical trial registered with www.clinicaltrials.gov (NCT00292552 [Gene Expression Omnibus Series ID: GSE76705], NCT03004417 [GSE133513], and NCT02986321).

2022-12-01·Journal of translational medicine2区 · 医学

The PDE4 inhibitor tanimilast shows distinct immunomodulatory properties associated with a type 2 endotype and CD141 upregulation

2区 · 医学

ArticleOA

作者: Gaudenzi, Carolina ; Villetti, Gino ; Civelli, Maurizio ; Tiberio, Laura ; Schioppa, Tiziana ; Facchinetti, Fabrizio ; Salvi, Valentina ; Passari, Mauro ; Sozio, Francesca ; Del Prete, Annalisa ; Govoni, Mirco ; Barbazza, Ilaria ; Nguyen, Hoang Oanh ; Sozzani, Silvano ; Bosisio, Daniela

Abstract:

Background:

Tanimilast is a novel and selective inhaled inhibitor of phosphodiesterase-4 in advanced clinical development for chronic obstructive pulmonary disease (COPD). Tanimilast is known to exert prominent anti-inflammatory activity when tested in preclinical experimental models as well as in human clinical studies. Recently, we have demonstrated that it also finely tunes, rather than suppressing, the cytokine network secreted by activated dendritic cells (DCs). This study was designed to characterize the effects of tanimilast on T-cell polarizing properties of DCs and to investigate additional functional and phenotypical features induced by tanimilast.

Methods:

DCs at day 6 of culture were stimulated with LPS in the presence or absence of tanimilast or the control drug budesonide. After 24 h, DCs were analyzed for the expression of surface markers of maturation and activation by flow cytometry and cocultured with T cells to investigate cell proliferation and activation/polarization. The regulation of type 2-skewing mediators was investigated by real-time PCR in DCs and compared to results obtained in vivo in a randomized placebo-controlled trial on COPD patients treated with tanimilast.

Results:

Our results show that both tanimilast and budesonide reduced the production of the immunostimulatory cytokine IFN-γ by CD4+T cells. However, the two drugs acted at different levels since budesonide mainly blocked T cell proliferation, while tanimilast skewed T cells towards a Th2 phenotype without affecting cell proliferation. In addition, only DCs matured in the presence of tanimilast displayed increased CD86/CD80 ratio and CD141 expression, which correlated with Th2 T cell induction and dead cell uptake respectively. These cells also upregulated cAMP-dependent immunosuppressive molecules such as IDO1, TSP1, VEGF-A and Amphiregulin. Notably, the translational value of these data was confirmed by the finding that these same genes were upregulated also in sputum cells of COPD patients treated with tanimilast as add-on to inhaled glucocorticoids and bronchodilators.

Conclusion:

Taken together, these findings demonstrate distinct immunomodulatory properties of tanimilast associated with a type 2 endotype and CD141 upregulation in DCs and provide a mechanistic rationale for the administration of tanimilast on top of inhaled corticosteroids.

2021-11-01·Drugs1区 · 医学

Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease

1区 · 医学

Review

作者: Mathioudakis, Alexander G ; Singh, Dave ; Lea, Simon

Phosphodiesterase (PDE) 4 inhibitors prevent the metabolism of cyclic adenosine monophosphate, thereby reducing inflammation. Inhaled PDE4 inhibitors aim to restrict systemic drug exposure to enhance the potential for clinical benefits (in the lungs) versus adverse events (systemically). The orally administered PDE4 inhibitor roflumilast reduces exacerbation rates in the subgroup of chronic obstructive pulmonary disease patients with a history of exacerbations and the presence of chronic bronchitis, but can cause PDE4 related adverse effects due to systemic exposure. CHF6001 is an inhaled PDE4 inhibitor, while inhaled ensifentrine is an inhibitor of both PDE3 and PDE4; antagonism of PDE3 facilitates smooth muscle relaxation and hence bronchodilation. These inhaled PDE inhibitors have both reported positive findings from early phase clinical trials, and have been well tolerated. Longer term trials are needed to firmly establish the clinical benefits of these drugs.

项与 Tanimilast 相关的新闻（医药）

2024-07-08

·药智网

呼吸领域——COPD，今年迎来两个重磅新药！

6月26日，美国FDA批准Verona（VRNA）公司的Ohtuvayre (ensifentrine)上市，作为维持疗法治疗慢性阻塞性肺病（COPD）成人患者。Verona新闻稿指出，该药是COPD治疗领域近20年以来首个获批上市的新机制吸入制剂。 7月3日，赛诺菲针对COPD的新药Dupixent (度普利尤单抗)获欧洲药品管理局（EMA）批准作为以血嗜酸性粒细胞水平升高为特征的不受控制的慢性阻塞性肺病（COPD）患者的附加维持治疗，成为COPD治疗领域的首个获批生物制剂。短短几天，COPD治疗领域就将迎来重塑，这一严重呼吸系统疾病的治疗格局或许有望在今年发生变革。 COPD 患者亟待新药慢性阻塞性肺疾病（COPD, chronic obstructive pulmonary disease）简称慢阻肺，根据慢性阻塞性肺疾病全球倡议（GOLD）2024版，COPD是一种常见的、可以预防和治疗的异质性疾病，一般是由长期接触有毒颗粒或气体引起的气道和（或）肺泡异常所致，并受到宿主因素影响，以气流受限及持续的呼吸道症状为主要特征。根据世界卫生组织统计，COPD已经成为人类的第三大死因，约有11%的人死于COPD。预计未来40年COPD的患病率将不断增加，到2060年每年可能会有超过540万人死于COPD及其相关疾病。2018年王辰院士在《The Lancet》上发表的研究显示，我国就有近1亿COPD患者，40岁以上成人COPD患病率达13.7%。 GOLD 2024中推荐的COPD的治疗和预防药物主要有吸入性糖皮质激素、支气管扩张剂、磷酸二酯酶-4抑制剂、抗生素、疫苗、黏液溶解剂及抗氧化剂。图1. COPD常见维持用药图片来源：GOLD 2024指南但同时，这些药物虽然对于COPD患者的症状有显著改善，但COPD急性加重的预防仍是目前的治疗难点。目前临床上接受三联方案治疗的慢阻肺病患者中，仍有 30%～40% 患者存在中度或重度急性加重。并且，由于COPD发病机制较为复杂，尚未完全明确，因此目前临床上极度缺乏针对病因的有效治疗药物。该领域甚至十余年未推出新药，COPD患者亟待新药。两个新药有望改变COPD治疗格局可喜的是，今年6月，美国FDA批准上市了二十年来首个COPD新机制吸入剂——Ensifentrine。随后，再生元/赛诺菲的生物制剂Dupilumab在欧洲获批上市，为COPD患者带来全新的用药选择。 Ensifentrine：首个获批的COPD新机制药物 Ensifentrine是Verona公司开发的一种小分子选择性磷酸二酯酶双抑制剂（PDE3/4）。PDE3/4在支气管平滑肌上广泛表达，Ensifentrine抑制PDE3/4后，提升支气管内cAMP，进而发挥支气管舒张和抗炎的双重作用。2024年6月，该药获FDA批准，作为维持疗法治疗慢性阻塞性肺病（COPD）成人患者，商品名：Ohtuvayre。该疗法在今年初曾被行业媒体Evaluate列为2024有望获批的10款重磅疗法之一，是20多年来具有新作用机制、用于COPD维持治疗的首个吸入式疗法。图2. Ensifentrine结构式图片来源：参考资料6 FDA此次批准基于ENHANCE-1和ENHANCE-2两项Ⅲ期临床研究数据。ENHANCE-1和ENHANCE-2都是随机、双盲、安慰剂对照的Ⅲ期研究，分别入组760和790名COPD成年患者。相较于安慰剂，Ensifentrine可以显著改善0-12小时内1秒钟平均用力呼吸曲线下面积（FEV1 AUC 0-12hr）。图3. 两个ENHANCE研究都达到了主要终点图片来源：Verona公司官网安全性方面，患者对Ensifentrine耐受良好，最常见的不良反应是鼻咽炎、高血压和背疼。值得一提的是，2021年6月，Verona公司授予优锐医药在大中华区临床开发和商业化ensifentrine的独家权利。2023年2月，优锐医药启动了Ensifentrine治疗COPD的中国Ⅲ期临床试验，该药或将很快惠及国内COPD患者。 Dupilumab：首个获批COPD的生物制剂除了Ensifentrine，再生元/赛诺菲的Dupilumab（达必妥，IL-4/13单抗）目前也已获EMA批准用于治疗COPD，今年后续也有望FDA获批。 7月3日，赛诺菲和再生元共同宣布度普利尤单抗（dupilumab，商品名：Dupixent）获欧洲药品管理局（EMA）批准作为以血嗜酸性粒细胞水平升高为特征的不受控制的慢性阻塞性肺病（COPD）患者的附加维持治疗。今年2月，美国FDA已受理Dupilumab治疗慢性阻塞性肺疾病（COPD）的补充生物制品许可申请（sBLA）并授予优先审评资格，作为患有病情不受控制COPD成年患者的附加维持治疗，该申请的结果预计在今年晚些时候公布。该药在中国也同步提交了上市许可申请，并获得了CDE受理。 5月20日，赛诺菲公布了达必妥治疗COPD的NOTUS Ⅲ期研究最新数据，其治疗组中伴有2型炎症特征（血嗜酸性粒细胞≥300/μl）的COPD患者急性加重年化率显著降低34%，且肺功能获得显著改善（此次度普利尤单抗EMA获批，也正是基于上述研究的积极结果），具体如下：主要终点：治疗52周中重度慢阻肺病急性加重年化率降低34% (p<0.001)。次要终点：第12周时，肺功能较基线改善超过两倍(139mL vs. 57mL;p<0.001)，并且该改善在第52周时得以维持(115mL vs. 54mL;p=0.018)。次要终点：第52周时，健康相关生活质量评分在数值上较基线改善更明显。次要终点：第52周时，呼吸道症状的严重程度在数值上降低较基线更为明显。长久以来，由于COPD的异质性，以往针对COPD的多数生物制剂都已沉戟，度普利尤单抗的获批极大的提振了领域内的研发信心。赛诺菲找到的突破口是2型炎症。最新研究结果显示，约20%-40%的COPD患者属于嗜酸性粒细胞水平升高的2型炎症型。Dupilumab是一款靶向IL-4受体α（IL-4Rα）的单克隆抗体，通过阻断IL-4/13与其受体复合物的结合来抑制IL-4/13介导的2型炎症反应。 Dupilumab此前已获批包括哮喘在内的数个自免领域的适应症，2023年销售额超100亿美元，其营收达到了赛诺菲整体收入的四分之一。通过2型炎症这一突破口，赛诺菲在免疫管线的布局可谓固若金汤。在研药物 MNC、国内药企竞逐COPD赛道 Ensifentrine和Dupilumab通过不同机制有望给不同COPD患者带来新的治疗方案。此外，COPD领域还有多个小分子和生物制剂已进入临床后期阶段。表1. COPD领域在研新药（部分）药品名称药品分类靶点研发单位 COPD适应症进展 Ensifentrine 小分子 PDE4;PDE3 Verona Pharma 美国获批上市度普利尤单抗 dupilumab 单抗 IL4RA 再生元/赛诺菲欧洲获批上市依特吉单抗 itepekimab 单抗 IL33 再生元临床Ⅲ期托雷奇单抗 tozorakimab 单抗 IL33 阿斯利康临床Ⅲ期贝那利珠单抗 benralizumab 单抗 IL5RA 阿斯利康临床Ⅲ期美泊利珠单抗 mepolizumab 单抗 IL5 葛兰素史克临床Ⅲ期艾特利单抗 astegolimab 单抗 IL1R;IL-33R 罗氏/安进临床Ⅲ期坦尼米司特 tanimilast 小分子 PDE4 凯西制药临床Ⅲ期 HPP737 小分子 PDE4 vTv Therapeutics /济川药业临床Ⅱ期 TQC-3721 小分子 PDE4;PDE3 正大天晴临床Ⅱ期 SSGJ-611 单抗 IL4R 三生国健临床Ⅱ期 9MW1911 单抗 IL1RL1 迈威生物临床Ⅱ期司普奇拜单抗 CM310 单抗 IL4RA 康诺亚临床Ⅱ期泽芦人单抗 tezepelumab 单抗 TSLP 安进/阿斯利康临床Ⅱ期 REGEND-001 肺前体细胞 IL33 吉美瑞生临床Ⅱ期 DBM-1152A 小分子 CHRM3;ADRB2 硕佰医药临床Ⅰ期 QX005N 单抗 IL4RA 荃信生物临床Ⅰ期 MG-ZG122 单抗 TSLP 麦济生物临床Ⅰ期 SHR-1905 单抗 TSLP 恒瑞医药临床申请 CM326 单抗 TSLP 康诺亚临床申请 SSGJ-621 单抗 IL33 三生国健临床申请 LQ-036 单抗 IL4R;IL4RA 洛启生物临床申请 QX007N 单抗 IL33 荃信生物临床申请数据来源：药智数据其中，以目前COPD领域在研新药的制剂类型分布来看，由小分子药物向生物药转变的风向似乎正在加速，生物制剂能够精准作用于特定的炎症通路，阻断免疫应答的关键环节也成为了越来越多的药企布局的原因。尤其是靶向IL-4、IL-5、IL-33等介导2型炎症的单抗是COPD治疗的热门机制，约占全球临床后期在研项目的一半以上，其中再生元的Dupilumab已获批上市；mepolizumab、benralizumab、astegolimab、itepekimab、tozorakimab等5个新药也均处于Ⅲ期临床阶段。预计很快，COPD领域就或许会因此而掀起异常治疗范式的变革，而率先冲线的度普利尤单抗，或许也会分得不小的市场份额。而国内领域，众多药企也在争相布局COPD赛道，并有多个新药已进入临床阶段。例如，正大天晴的TQC-3721已进入临床Ⅱ期阶段，该药与Ensifentrine同为PDE3/4抑制剂；三生国健的SSGJ-611是一款人源化抗IL-4Rα单克隆抗体，2023年9月获批开展慢性阻塞性肺疾病适应症Ⅱ期临床试验。其他进展较快的还有康诺亚的IL-4Rα单抗司普奇拜单抗（CM310）、吉美瑞生的肺前体细胞REGEND001等。不过，就全球COPD在研新药领域的竞争格局上MNC药企的临床进度普遍高于国内，临床Ⅱ期以上的8款药物中，清一色的海外药企。国内药企要想在短期内赶超MNC的难度不小。结语 COPD患者的治疗背景复杂，发育情况、吸烟史、生物标志物水平等的不同也带来了治疗效果的不同，对于COPD患者急性加重的治疗，传统的药物往往效果不佳。此次Ensifentrine与Dupixent的获批为COPD的治疗带来了新的选择。后续，COPD治疗格局或许也会因这两款新药，而发生巨大重构，请拭目以待。参考文献： World Health Organization:The top 10 causes of death World Health Organization:global burden of disease estimats Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet. 2018 Apr 28; 391(10131):1706-1717 GOLD 2024指南 Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials). Am J Respir Crit Care Med. 2023 Aug 15;208(4):406-416. https://ohtuvayrehcp.com/files/Ohtuvayre-US-Prescribing-Information.pdf 来源 | 博药（药智网获取授权转载）撰稿 | 泠然责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信）阅读原文，是昨天最受欢迎的文章哦

上市批准信使RNA疫苗

2024-05-16

·BioSpace

Chiesi to Present New Data Showcasing Depth of Respiratory Leadership at the American Thoracic Society 2024 International Conference

Presentations will highlight new data in respiratory conditions, including asthma and chronic obstructive pulmonary disease (COPD) Data to be presented include new six-month results from a study of a single-inhaler triple therapy in patients with asthma and new pharmacokinetic studies of tanimilast, an inhaled phosphodiesterase-4 inhibitor, in patients with COPD Chiesi is a Sapphire level sponsor of the annual ATS Research Program Benefit to support new researchers in respiratory disease CARY, N.C., May 16, 2024 (GLOBE NEWSWIRE) -- Chiesi, USA (Formerly Known As Cornerstone Therapeutics) (key-A-zee), the U.S. affiliate of Chiesi Farmaceutici, an international research-focused healthcare Group (Chiesi Group), today announced the presentation of eight abstracts from Chiesi’s global respiratory research portfolio at the American Thoracic Society (ATS) 2024 International Conference in San Diego from May 17-22, 2024. In addition, Chiesi will showcase its commitment to innovation through additional sponsorship opportunities aimed at addressing needs within the respiratory professional community through multiple avenues, including as the largest supporter of the annual ATS Research Program Benefit. “Chiesi’s Air franchise has a robust history spanning multiple decades of delivering innovative medicines in Europe, and we’re excited to share some of the research supporting our global scientific advancements in the respiratory therapeutic area at ATS," said Carmen Dell’Anna, head of global medical affairs, Chiesi Group. "Alongside updates on our scientific progress, the Chiesi expert-led Innovation Hub will focus on discussing the role of small airway dysfunction and persistent airflow limitation in asthma. With a solid presence at the ATS conference this year, we affirm our distinctive commitment to address respiratory-related burdens by focusing on creating shared value for people and the planet.” Chiesi is presenting eight abstracts featuring the company’s latest advancements in research across asthma and chronic obstructive pulmonary disease (COPD). These presentations underscore Chiesi's dedication to advancing scientific knowledge and improving outcomes for people living with respiratory disease with preclinical and clinical stage global studies. Data accepted for presentation include: Asthma Anti-inflammatory Effects of Tanimilast in Two Murine House Dust Mite (HDM)-driven Models of Asthma Poster Session B79: Airway Smooth Muscle in Asthma (May 20, 11:30 a.m. – 1:15 p.m. PT) Extrafine Formulation Single-inhaler Triple Therapy Improves Lung Function After Six Months of Treatment in Patients With Asthma: Trimaximize Study Poster Session C31: What’s New in Clinical Asthma (May 21, 11:30 a.m. – 1:15 p.m. PT) Chronic Obstructive Pulmonary Disease (COPD) Pharmacokinetics, Safety And Tolerability Of Tanimilast Following Single Administration In Subjects With Mild, Moderate And Severe Renal Impairment Poster Session A27: Emerging Treatments and Therapeutic Strategies in COPD: Results of Clinical Trials and Observational Studies (May 19, 9:15-11:15 a.m. PT) Pharmacokinetics, Safety And Tolerability Of Tanimilast Following Single Administration In Subjects With Mild, Moderate And Severe Hepatic Impairment Poster Session A27: Emerging Treatments and Therapeutic Strategies in COPD: Results of Clinical Trials and Observational Studies (May 19, 9:15-11:15 a.m. PT) Effects Of Single Inhaler Combinations Of Extrafine BDP/FF/GB And Extrafine BDP/FF on Lung Hyperinflation And Exercise Endurance Time in Subjects With COPD Poster Session B80-2: Abnormalities in Structure and Function in COPD (May 20, 11:30 a.m.-1:15 p.m. PT) Other Respiratory Conditions Is Onsite Spirometry Quality Predicting the Quality of Home Spirometry? Poster Session A38: Highlights of Behavioral Science and Health Services Research (May 19, 11:30 a.m.-1:15 p.m. PT) Development of a Multi-biomarker Assay for Serum Proteins by the Prognostic Lung Fibrosis Consortium (PROLIFIC) Poster Session B46: Up and Coming: ILD Biomarkers (May 20, 11:30 a.m. – 1:15 p.m. PT) Proteomic Analysis of Right Ventricular Hypertrophy in Experimental Pulmonary Arterial Hypertension and the Impact of Therapeutic Intervention Poster Session C60: Beachcombing for Gold: -Omics, Inflammation, and the RV in PH (May 21, 11:30 a.m.-1:15 p.m. PT) “Despite advances in respiratory care, many individuals are waiting for new ways to address their specific asthma symptoms,” said Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America. “The creation of innovative medicines offers increased treatment options and opportunities for treatment better tailored to an individual’s specific needs. It’s also important to address the climate crisis and take steps to directly combat the underlying environmental drivers of respiratory diseases like asthma and COPD. By tackling problems with multiple approaches, we can bridge the gap in care and achieve better outcomes for people living with respiratory disease.” In addition to presenting research, Chiesi is engaging with the respiratory healthcare community through its support of early career investigator programs. The company is a Sapphire level sponsor of the Annual ATS Research Program Benefit on Saturday, May 18, from 6-7:30 p.m. PT. Chiesi is also sponsoring a one-year research grant for a respiratory disease researcher to advance the understanding of obstructive lung disease. About Chiesi USA Chiesi USA, Inc., headquartered in Cary, North Carolina, is a specialty pharmaceutical company focused on the commercialization of products for the hospital and target office-based specialties. Chiesi USA is a wholly owned subsidiary of privately-owned Chiesi Farmaceutici S.p.A, a global R&D-focused pharmaceutical company based in Parma, Italy. In the United States, the company delivers therapies and enhances care for patients in the areas of acute cardiology, neonatology, cystic fibrosis and rare diseases. Recognized as a Certified B Corporation™, Chiesi is dedicated to improving the health and well-being of its communities through its employee-led corporate social responsibility program, Chiesi in the Community. Innovation, collaboration and impact are the cornerstones of the Chiesi culture. For more information, visit . About Chiesi Group Chiesi is an international, research-focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company’s mission is to improve people’s quality of life and act responsibly towards both the community and the environment. By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi’s commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we’re part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035. With over 85 years of experience, Chiesi is headquartered in Parma (Italy), operates in 31 countries, and has more than 6,500 employees. The Group’s research and development center in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden. For further information please visit . Contacts Chiesi USA: Gentry Lassiter, +1 (984) 800-5262, us.mediarelations@chiesi.com PP-AR-0023 v1.0 PDF available:

2022-06-13

·药通社

CDE周报 | 45个1类新药受理号被承办，驯鹿生物伊基仑赛注射液报上市！

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。引言：一周一见的CDE周报来了！详情见下（文中统计结果不包括补充申请&进口再注册）。创新药承办情况2022年6月6日-12日CDE共承办45个创新药受理号，其中包括了化药受理号18个，生物制品受理号26个,中药受理号1个。此次的45个1类新药受理号包括1个上市注册申请和44个临床试验申请，唯一的上市注册申请为南京驯鹿生物医药有限公司关于伊基仑赛注射液的上市注册申请。化药创新药：此次申报的化学药分别为：BI 907828片、SYHX2009片、QY101软膏、SAL0112片、CHF6001吸入粉雾剂、LNP023胶囊、HRS-9821吸入混悬液、吸入用Ensifentrine混悬液、XNW1011胶囊。BI 907828片：BI 907828片是一种MDM2 拮抗剂。MDM2全称为mouse doubleminute 2 homolog，是一种E3泛素连接酶。各类研究发现，当MDM2发生扩增或MDM2蛋白由于基因调控不当而过表达时，肿瘤细胞往往会加快生长，而且对免疫疗法的耐药性会更高。有研究表明MDM2能通过多种机制帮助肿瘤生长并逃避免疫系统。SYHX2009片：该药品为首次被承办，暂未查到该药相关信息。QY101软膏：QY101是由启元生物自主研发的一类创新药，已获批适应症为特应性皮炎。QY101是非激素、非甾体类抗炎的磷酸二酯酶4 (PDE4)抑制剂，特应性皮炎发病已被证明与PDE4的过度活化有关，PDE4抑制剂可以对其进行有效的治疗。QY101软膏剂在动物实验中表现出良好的PK特性，优异的药效与高度的安全性，可以适应不同年龄段人群的治疗需求。 SAL0112片：SAL0112片是胰高血糖素样肽-1受体（GLP-1R）的口服小分子偏向激动剂，是深圳信立泰自主研发的创新小分子化学药物，此次临床申请对应适应症为：适用于成人肥胖患者或伴发一种及以上与体重相关危险因素的超重患者的体重管理。CHF6001吸入粉雾剂：CHF6001是一种PDE4抑制剂，拟用于COPD和慢性支气管炎的治疗。LNP023胶囊：LNP023胶囊是诺华的一种首创口服因子B抑制剂，能高效抑制补体替代通路中因子B，因子B是补体系统替代途径的关键丝氨酸蛋白酶。HRS-9821吸入混悬液：该药品为首次被承办，暂未查到该药相关信息。吸入用Ensifentrine混悬液：ensifentrine是一款PDE3和PDE4双抑制剂新药，可凭借单个化合物同时实现支气管扩张和抗炎效果。XNW1011胶囊：XNW1011胶囊是杏联药业的一款 BTK 抑制剂生物制品创新药：此次申报的生物制品分别为：CagriSema注射液、MK-4830注射液、ZS801注射液、HB0036注射液、注射用ZGGS18、TX103嵌合抗原受体T细胞注射液、QL1604注射液、B013注射液、重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白注射液、注射用FDA022抗体偶联剂、注射用DB-1305、ASKB589注射液、重组抗EpCAM-CD3抗体注射液、自体抗CLL-1嵌合抗原受体T细胞注射液、阴道用四联乳杆菌活菌胶囊、伊基仑赛注射液。CagriSema注射液：CagriSema是诺和诺德的一款复方制剂，包含长效amylin（胰淀素）类似物cagrilintide和长效GLP-1（胰高血糖素样肽-1）受体激动剂司美格鲁肽两种成分。该药拟用于体重管理。MK-4830注射液： MK-4830是一款first-in-class 抗ILT4 （免疫球蛋白样转录子4）单抗，与T细胞靶向抗体(例如抗PD-1，抗CTLA-4)不同，抗ILT4被认为可以减轻肿瘤微环境中耐受性髓细胞的免疫抑制作用。ZS801注射液：ZS801是一种rAAV基因药物，临床适应症为B型血友病。HB0036注射液：HB0036 是一种靶向程序性死亡受体配体 1（PD-L1）和 T 细胞免疫球蛋白和ITIM 结构域（TIGIT）的双特异性抗体，能同时高特异性的与 PD-L1 和 TIGIT 这两个靶点结合、阻断二者介导的免疫抑制，重新激活免疫系统对肿瘤细胞的杀伤，最终实现协同抗肿瘤作用。注射用ZGGS18：ZGGS18是一种重组人源化抗VEGF/TGF-β的双功能抗体融合蛋白，可以特异性地结合血管内皮生长因子(VEGF)和“捕获”转化生长因子-β(TGFβ)，起到抑制肿瘤新生血管形成和降低肿瘤转移发生等协同抑制肿瘤生长的多重作用。QL1604注射液：QL1604注射液是由齐鲁制药有限公司研发的一种抗PD-1单克隆抗体注射液。B013注射液：该药品为首次被承办，暂未查到该药相关信息。注射用DB-1305：该药品为首次被承办，暂未查到该药相关信息。ASKB589注射液：ASKB589注射液为江苏奥赛康自主研发、具有自主知识产权的抗肿瘤生物新药，其主要通ADCC和补体依赖的细胞毒作用（CDC）杀伤肿瘤细胞，拟用于胃及胃食管结合部腺癌、胰腺癌等适应症。伊基仑赛注射液：伊基仑赛是一款全人源BCMA嵌合抗原受体（CAR）自体T细胞注射液（研发代号CT103A）。该药由驯鹿生物和信达生物联合开发，可凭借慢病毒为基因载体转染自体T细胞，CAR包含全人源scFv、CD8a铰链和跨膜、4-1BB共刺激和CD3ζ激活结构域。此前，伊基仑赛已获得CDE授予突破性治疗品种，用于治疗复发/难治性多发性骨髓瘤。2022年2月，美国FDA授予CT103A孤儿药资格，用于治疗复发/难治性多发性骨髓瘤。中药创新药：此次唯一申报的中药创新药为一力制药股份有限公司关于小儿香薷颗粒的临床试验申请。创新药承办情况改良型新药承办情况2022年6月6日-12日CDE共承办9个改良型新药受理号，均为临床试验申请。其中，包括了3品规生物制品相关申请和6品规化药相关申请。帕博利珠单抗注射液：帕博利珠单抗是一款可与PD－1受体结合的单克隆抗体，可阻断PD-1与PD-L1、PD-L2的相互作用，解除PD-1通路介导的免疫应答抑制，恢复肿瘤特异性T细胞免疫。古塞奇尤单抗注射液：古塞奇尤单抗是一种特异性抗IL-23单克隆抗体，可通过与IL-23的p19亚基结合，阻断IL-23作用。IL-23 是银屑病致病核心通路IL-23/Th17轴的调控因子，对整个通路起调控作用。改良型新药承办情况注册分类：3类注册分类：4类注册分类：5类

免疫疗法抗体创新药小分子药物抗体药物偶联物

100 项与 Tanimilast 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12800

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
慢性支气管炎	临床3期	美国	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	阿根廷	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	澳大利亚	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	奥地利	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	保加利亚	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	智利	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	捷克	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	德国	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	希腊	CHIESI Farmaceutici SpA	2021-06-24
慢性支气管炎	临床3期	匈牙利	CHIESI Farmaceutici SpA	2021-06-24

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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


NCT05431426 (ATS2024) 人工标引	临床1期	肾功能不全	24	tanimilast (renal impairment)	觸選築衊糧餘鏇餘鹽憲(淵齋繭廠襯齋選積鹹夢) = There was no clear trend of increased systemic exposure with increasing RI severity 觸鹹齋鹹衊簾憲憲築範 (鑰憲鹽鹽繭憲鹹淵餘觸 ) 更多	积极	2024-05-19
ATS2024	N/A	肝功能不全	-	Tanimilast 800μg DPI	襯觸壓選鹹觸觸繭衊獵(積窪夢齋淵衊襯觸膚醖) = 襯襯繭遞糧窪簾願蓋構願鹹鑰顧淵鹹繭鹽蓋鑰 (積襯壓網積壓範醖願齋 ) 更多	-	2024-05-19
				Tanimilast (Healthy Volunteers)	襯觸壓選鹹觸觸繭衊獵(積窪夢齋淵衊襯觸膚醖) = 觸構積積鹹鑰夢廠艱積願鹹鑰顧淵鹹繭鹽蓋鑰 (積襯壓網積壓範醖願齋 ) 更多
ATS2024	N/A	哮喘	-	Tanimilast 3mg/kg b.i.d.	網憲顧衊膚廠觸鬱鑰遞(鏇艱積獵夢夢鹹膚選製) = 顧窪選簾鹽繭選製鏇蓋艱繭構艱廠憲顧淵積糧 (獵範膚壓觸鏇遞簾繭願 ) 更多	-	2024-05-19
				Tanimilast 1mg/kg + Budesonide	網憲顧衊膚廠觸鬱鑰遞(鏇艱積獵夢夢鹹膚選製) = 鑰繭膚簾廠壓鬱艱繭願艱繭構艱廠憲顧淵積糧 (獵範膚壓觸鏇遞簾繭願 ) 更多
NCT04756960 (CTgov)	临床1期	慢性阻塞性肺疾病	8	CHF6001	願積構築築構艱壓鹹憲(選糧鏇艱願夢願膚艱廠) = 蓋鏇願觸選觸廠鏇憲願鏇繭網壓襯鹹醖鹹餘夢 (鹹壓膚積築壓鏇顧窪齋, 積積壓餘鬱襯糧醖築衊 ~ 廠淵鑰簾衊蓋鏇範鹹壓) 更多	-	2024-03-18
ERS2019	临床3期	慢性阻塞性肺疾病 leukotriene B4 \| interleukin 8 \| macrophage inflammatory protein 1β ... 更多	61	CHF6001 1600µg	選淵積簾鏇鏇獵構積遞(憲選醖襯觸憲糧壓選觸) = 淵壓餘築簾鏇壓夢鹽齋窪遞廠顧選窪膚蓋鹽鬱 (遞鬱醖獵夢顧鹹繭觸夢 ) 更多	积极	2019-09-28
				CHF6001 3200µg	選淵積簾鏇鏇獵構積遞(憲選醖襯觸憲糧壓選觸) = 壓衊製廠製餘鏇築鹽鏇窪遞廠顧選窪膚蓋鹽鬱 (遞鬱醖獵夢顧鹹繭觸夢 ) 更多
Pubmed \| Int J Chron Obstruct Pulmon Dis	N/A	-	-	CHF6001	糧齋襯壓齋鏇積鹽構鏇(醖鹹構鹽簾簾淵鬱餘襯) = 醖鹹廠醖艱觸艱顧壓積顧淵鹽齋齋簾願淵醖獵 (鏇艱鑰廠膚構壓襯鹹願 ) 更多	-	2018-10-01
				Placebo	餘遞齋願糧鑰鑰鏇製範(糧膚襯遞壓醖艱蓋遞膚) = 鏇鹽遞壓蓋遞膚齋簾鑰鹽壓鑰糧夢鑰膚積觸顧 (繭衊簾鹹觸憲鬱夢繭憲 )
ERS2014	N/A	慢性阻塞性肺疾病	-	CHF6001	壓淵鬱壓壓鹽簾鹽鏇範(獵夢餘製鑰蓋築壓獵獵) = 簾膚鏇夢廠艱鬱鏇襯願選糧膚選鏇窪築鏇鏇廠 (襯築鹽淵顧壓獵醖艱鏇, 1nM)	-	2014-09-01
				Roflumilast	壓淵鬱壓壓鹽簾鹽鏇範(獵夢餘製鑰蓋築壓獵獵) = 顧觸鬱積齋艱廠觸築窪選糧膚選鏇窪築鏇鏇廠 (襯築鹽淵顧壓獵醖艱鏇, 1000nM)
ERS2012	N/A	维持	66	NEXThaler	憲鬱構獵鹹製窪鏇獵網(鹹鹽壓餘憲糧積齋願簾) = 網憲獵築網廠窪壓衊糧網範簾範夢壓遞糧齋繭 (艱構衊選憲淵顧衊積膚 ) 更多	积极	2012-09-01
				NEXThaler	憲鬱構獵鹹製窪鏇獵網(鹹鹽壓餘憲糧積齋願簾) = 糧鏇淵膚鏇鑰憲壓願鹽網範簾範夢壓遞糧齋繭 (艱構衊選憲淵顧衊積膚 ) 更多
ERS2011	N/A	慢性阻塞性肺疾病 \| 哮喘	-	NEXT DPI® dry powder inhaler	壓衊齋鏇餘鏇網艱齋繭(壓願鹹膚糧齋築顧鹹蓋) = A total of 7 AEs were reported in 5 patients, no one related with the use of NEXT DPI® or severe in intensity. No Severe Adverse Events were reported. 觸醖憲衊願蓋餘鹽膚網 (窪繭壓鑰築遞鏇遞艱製 )	-	2011-09-01
				NEXT DPI® dry powder inhaler