(Galicaftor) - 药物靶点：CFTR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Galicaftor (USAN/INN)、ABBV 2222、ABBV-2222

+ [2]

靶点

CFTR

作用机制

CFTR调节剂(囊性纤维化跨膜传导调节因子调节剂)

治疗领域

遗传病与畸形消化系统疾病呼吸系统疾病+ [1]

在研适应症-

非在研适应症

原研机构

在研机构

非在研机构

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C28H21F4NO7

InChIKeyQVDYQHXNAQHIKH-TZIWHRDSSA-N

CAS号1918143-53-9

关联

17

项与 Galicaftor 相关的临床试验

NCT05538585 / Completed临床1期

A Food-Effect Study for the Safety and Assessment of Pharmacokinetics of Navocaftor and Galicaftor.

Cystic Fibrosis (CF) is a rare, life-threatening, genetic disease that affects the lungs and digestive system, significantly impairing the quality of life, with those affected having a median age of death at 40. The objectives of this study are to assess the effect of food on the safety and pharmacokinetics of navocaftor and galicaftor.

开始日期2022-09-27

申办/合作机构

AbbVie, Inc.

NCT05530278 / Completed临床1期

Assessment of Multiple-Dose Pharmacokinetics and Safety of the Co-administration of Galicaftor, Navocaftor and ABBV-576 and Potential of ABBV-576 for CYP3A Induction in Healthy Volunteers

Cystic Fibrosis (CF) is a rare, life-threatening, genetic disease that affects the lungs and digestive system, significantly impairing the quality of life, with those affected having a median age of death at 40. The main objectives of this study are to assess the safety and pharmacokinetics of the combination therapy of galicaftor/navocaftor/ABBV-576.

开始日期2022-09-20

申办/合作机构

AbbVie, Inc.

NCT04853368 / Terminated临床2期

A Phase 2 Study of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation

Cystic Fibrosis (CF) is a rare, life-threatening, genetic disease that affects the lungs and digestive system, significantly impairing the quality of life, with those affected having a median age of death at 40. The main objective of this study is to assess how safe and effective is the combination therapy of galicaftor/navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 in adult participants with CF who are homozygous or heterozygous for the F508del mutation in each arm.
Galicaftor/Navocaftor/ABBV-119 combination therapy and Galicaftor/Navocaftor/ABBV-576 is being developed as an investigational drug for the treatment of CF. Study doctors place participants in 1 of the 4 groups, called treatment arms. Each group receives a different treatment. Around 90 adult participants with a diagnosis of CF will be enrolled in the study around approximately 35 sites worldwide.
Participants in arm 1 will receive oral capsules of galicaftor/navocaftor dual combination for 28 days followed by galicaftor/navocaftor/ABBV-119 triple combination for 28 days. Participants in arms 2 and 3 will receive the galicaftor/navocaftor/ABBV-119 triple combination or placebo for 28 days. Participants in arm 4 will receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days. For all study arms, ABBV-576, galicaftor, navocaftor, will be given once daily and ABBV-119 twice a day.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

开始日期2021-09-20

申办/合作机构

AbbVie, Inc.

100 项与 Galicaftor 相关的临床结果

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100 项与 Galicaftor 相关的转化医学

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100 项与 Galicaftor 相关的专利（医药）

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9

项与 Galicaftor 相关的文献（医药）

2023-08-15·Biochemistry

Computational Exploration of Potential CFTR Binding Sites for Type I Corrector Drugs.

Article

作者: Mitchell, Alexis ; Johnson, Quentin R ; Girard, Christian ; Ramsdell, Havanna ; Henager, Marissa E ; Lester, Anna ; Dixon, Brandon ; Poulos, Jack ; Evans, Claudia N ; Reber, Callista ; Spinney, Allison ; Herring, Caitlin ; Sandman, Madeline ; Turlington, Mark

Cystic fibrosis (CF) is a recessive genetic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The recent development of a class of drugs called "correctors", which repair the structure and function of mutant CFTR, has greatly enhanced the life expectancy of CF patients. These correctors target the most common disease causing CFTR mutant F508del and are exemplified by the FDA-approved VX-809. While one binding site of VX-809 to CFTR was recently elucidated by cryo-electron microscopy, four additional binding sites have been proposed in the literature and it has been theorized that VX-809 and structurally similar correctors may engage multiple CFTR binding sites. To explore these five binding sites, ensemble docking was performed on wild-type CFTR and the F508del mutant using a large library of structurally similar corrector drugs, including VX-809 (lumacaftor), VX-661 (tezacaftor), ABBV-2222 (galicaftor), and a host of other structurally related molecules. For wild-type CFTR, we find that only one site, located in membrane spanning domain 1 (MSD1), binds favorably to our ligand library. While this MSD1 site also binds our ligand library for F508del-CFTR, the F508del mutation also opens a binding site in nucleotide binding domain 1 (NBD1), which enables strong binding of our ligand library to this site. This NBD1 site in F508del-CFTR exhibits the strongest overall binding affinity for our library of corrector drugs. This data may serve to better understand the structural changes induced by mutation of CFTR and how correctors bind to the protein. Additionally, it may aid in the design of new, more effective CFTR corrector drugs.

2021-05-01·American journal of respiratory cell and molecular biology

Novel Correctors and Potentiators Enhance Translational Readthrough in CFTR Nonsense Mutations

Article

作者: Peng, Ning ; Conrath, Katja ; Mutyam, Venkateshwar ; Singh, Ashvani K. ; Li, Yao ; Tang, Li Ping ; Sharma, Jyoti ; Chen, Jianguo ; Falk Libby, Emily ; Rowe, Steven M.

Premature-termination codons (PTCs) in CFTR (cystic fibrosis [CF] transmembrane conductance regulator) result in nonfunctional CFTR protein and are the proximate cause of ∼11% of CF-causing alleles, for which no treatments exist. The CFTR corrector lumacaftor and the potentiator ivacaftor improve CFTR function with terminal PTC mutations and enhance the effect of readthrough agents. Novel correctors GLPG2222 (corrector 1 [C1]), GLPG3221 (corrector 2 [C2]), and potentiator GLPG1837 compare favorably with lumacaftor and ivacaftor in vitro. Here, we evaluated the effect of correctors C1a and C2a (derivatives of C1 and C2) and GLPG1837 alone or in combination with the readthrough compound G418 on CFTR function using heterologous Fischer rat thyroid (FRT) cells, the genetically engineered human bronchial epithelial (HBE) 16HBE14o^- cell lines, and primary human cells with PTC mutations. In FRT lines pretreated with G418, GLPG1837 elicited dose-dependent increases in CFTR activity that exceeded those from ivacaftor in FRT-W1282X and FRT-R1162X cells. A three-mechanism strategy consisting of G418, GLPG1837, and two correctors (C1a + C2a) yielded the greatest functional improvements in FRT and 16HBE14o^- PTC variants, noting that correction and potentiation without readthrough was sufficient to stimulate CFTR activity for W1282X cells. GLPG1837 + C1a + C2a restored substantial function in G542X/F508del HBE cells and restored even more function for W1282X/F508del cells, largely because of the corrector/potentiator effect, with no additional benefit from G418. In G542X/R553X or R1162X/R1162X organoids, enhanced forskolin-induced swelling was observed with G418 + GLPG1837 + C1a + C2a, although GLPG1837 + C1a + C2a alone was sufficient to improve forskolin-induced swelling in W1282X/W1282X organoids. Combination of CFTR correctors, potentiators, and readthrough compounds augments the functional repair of CFTR nonsense mutations, indicating the potential for novel correctors and potentiators to restore function to truncated W1282X CFTR.

2020-09-01·The Journal of pharmacology and experimental therapeutics

Correction to “Biological Characterization of F508delCFTR Protein Processing by the CFTR Corrector ABBV-2222/GLPG2222”

Article

作者: T. R. Neelands ; C. Tse ; B. Liu ; Y. Fan ; P. R. Kym ; H. Y. Ren ; A. K. Singh ; A. M. Manelli ; C. Balut ; A. M. Swensen ; X. Wang ; K. Conrath ; Y. Jia ; X. B. Searle ; S. Alani ; T. A. Vortherms ; W. Gao ; T. C. Hwang ; D. Cyr

1

项与 Galicaftor 相关的新闻（医药）

2021-08-24

·Pharmaceutical Technology

Current and future players in the cystic fibrosis market

The currently available marketed drugs for cystic fibrosis (CF) target multiple aspects of the disease. Inhaled antibiotics are used for the treatment of chronic lung infections, mucolytic agents are used for reducing the viscosity of the mucus in the lungs, pancreatic enzyme replacement therapies (PERTs) are used for the treatment of CF-related exocrine pancreatic insufficiency (EPI), and CF transmembrane conductance regulator (CFTR) modulators enhance CFTR function, targeting the underlying cause of disease. The disease-modifying nature of CFTR modulators has transformed the treatment paradigm for CF over the last decade, setting a trend that is likely to persist to 2030. More than a dozen pharmaceutical companies make up the current players in the CF market (Figure). Vertex is the clear market leader, dominating the CF space with four marketed CFTR modulators available throughout the seven major markets (7MM) (US, France, Germany, Italy, Spain, UK and Canada), including Kalydeco (ivacaftor), Orkambi (lumacaftor/ivacaftor), Symdeko/Symkevi (tezacaftor/ivacaftor and ivacaftor), and Trikafta/Kaftrio (elexacaftor, tezacaftor, ivacaftor). Since the global approval of Kalydeco in 2012, Vertex has greatly expanded the number of CF-related mutations that are eligible for CFTR modulator treatment across all age groups. Currently, Vertex’s Trikafta/Kaftrio is the world’s first triple-combination therapy for which approximately 90% of the CF population will likely be eligible. While Vertex is currently the only company with products in the CFTR modulator drug class, other players stand out with marketed products in other drug classes. Chiesi possesses two inhaled antibiotic products, Bramitob/Bethkis (tobramycin) in the US and five major European markets (5EU) (France, Germany, Italy, Spain and the UK) and Quinsair (levofloxacin) in the 5EU, as well as the mucolytic Bronchitol (mannitol) in the US and the PERT product Pertzye (pancrelipase) in the US. Two other key companies include Viatris (formerly Mylan), which owns the most widely-used inhaled antibiotic therapies, TOBI (tobramycin) and TOBI Podhaler (tobramycin inhalation powder), and Nestlé HealthScience, which owns two PERT products, Zenpep (pancrelipase) and Viokace (pancrelipase). The rest of the pharmaceutical companies with marketed drugs used for the treatment of CF include Gilead, Teva, Genentech, AbbVie, Vivus, Horizon Therapeutics and Pharmaxis. Vertex and AbbVie are the only two companies with clear stakes in both the current and future CF market. Vertex is currently pursuing label expansion for Kalydeco to CF patients ages 0 months to less than 12 months in Canada, and Trikafta/Kaftrio to pediatric CF patients ages 2-5 years in the US and 2-11 years in the 5EU and Canada. Additionally, two new products from this company are expected to launch within the next five years: VX-561 and VX-121 + tezacaftor + VX-561. Currently, AbbVie markets Creon, the most widely used PERT by CF patients. The company has two pipeline agents, ABBV-3067, a CFTR potentiator that is being studied in late-stage Phase II trials alone and in combination with galicaftor (ABBV-2222), a CFTR corrector. If successful, AbbVie will be Vertex’s first competitor in the CFTR modulator market. Laurent Pharmaceuticals is expected to be the only new player in the CF space by 2030. It is currently developing an anti-inflammatory agent, LAU-7b (fenretinide), for reducing the levels of inflammation and the severity of pulmonary infections with Pseudomonas aeruginosa. While this pipeline agent has an innovative mechanism of action and is a first-in-class drug, the company is a novice within the CF field and has not yet brought a drug to market. Due to the limited number of pipeline agents in late-stage development, GlobalData anticipates that the current players in the CF market will likely maintain their competitive positions by 2030. Related Report Cystic Fibrosis – Global Drug Forecast and Market Analysis to 2030 Get the Report Latest report from Browse over 50,000 other reports on our store. Visit GlobalData Store

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100 项与 Galicaftor 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11724	-	-	DB14894

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
囊性纤维化	临床2期	澳大利亚	Galapagos NV	2017-01-01
囊性纤维化	临床2期	比利时	Galapagos NV	2017-01-01
囊性纤维化	临床2期	捷克	Galapagos NV	2017-01-01
囊性纤维化	临床2期	德国	Galapagos NV	2017-01-01
囊性纤维化	临床2期	爱尔兰	Galapagos NV	2017-01-01
囊性纤维化	临床2期	英国	Galapagos NV	2017-01-01

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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


NCT03969888 (CTgov)	临床2期	囊性纤维化	78	Placebo ABBV-2222+ABBV-3067 (ABBV-3067 50 mg + Placebo for ABBV-2222)	齋選觸襯壓簾壓夢遞糧(艱鹽鹹製鹹鹹膚觸壓築) = 餘鹹範蓋鏇蓋範艱鹽膚顧廠選艱簾築廠窪蓋糧 (襯繭網簾觸鬱壓壓膚艱, 遞壓憲淵遞觸鏇鏇願壓 ~ 積淵鏇積醖網淵壓糧積) 更多	-	2023-06-28
				Placebo ABBV-2222+ABBV-3067 (ABBV-3067 150 mg + Placebo for ABBV-2222)	齋選觸襯壓簾壓夢遞糧(艱鹽鹹製鹹鹹膚觸壓築) = 淵淵鏇顧齋築範積憲範顧廠選艱簾築廠窪蓋糧 (襯繭網簾觸鬱壓壓膚艱, 艱構壓窪憲願鏇顧膚齋 ~ 觸網選夢繭醖廠憲醖選) 更多
NCT03119649 (FLAMINGO, Pubmed \| J Cyst Fibros) 人工标引	临床2期	囊性纤维化	59	GLPG2222	憲簾餘齋鹹艱襯鏇觸獵(憲壓蓋壓顧鬱願鹹廠壓) = 壓構範構鑰築顧範繭觸選鏇窪製鏇鏇鹽築憲範 (鹽選繭齋衊餘遞壓觸繭 )	不佳	2019-09-01
NCT03119649 (FLAMINGO, CTgov)	临床2期	囊性纤维化	59	placebo+GLPG2222 100 mg (Cohort A: GLPG2222 100 mg QD)	衊夢壓醖遞鹽醖獵願鬱(餘醖衊壓憲顧憲膚壓衊) = 鹹觸膚壓鬱鬱範構繭壓鹽繭襯齋壓艱鹹衊簾齋 (廠遞憲衊憲衊壓廠艱鑰, 鹽蓋選壓齋艱願遞齋衊 ~ 遞衊醖繭獵繭築鹽鹹遞) 更多	-	2018-11-16
				placebo+GLPG2222 200 mg (Cohort B: GLPG2222 200 mg QD)	衊夢壓醖遞鹽醖獵願鬱(餘醖衊壓憲顧憲膚壓衊) = 憲獵淵範築積鬱鏇壓鬱鹽繭襯齋壓艱鹹衊簾齋 (廠遞憲衊憲衊壓廠艱鑰, 製醖獵廠齋網艱廠壓艱 ~ 觸鹹簾構衊顧窪壓選醖) 更多