Discontinued Drugs for the Treatment of Cardiovascular Disease from 2016 to 2018

被引:18
|
作者
Li, Tingting [1 ]
Jiang, Sida [1 ]
Ni, Bingwei [2 ]
Cui, Qiuji [3 ]
Liu, Qinan [3 ]
Zhao, Hongping [3 ]
机构
[1] China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China
[2] China Pharmaceut Univ, Sch Engn, Nanjing 210009, Jiangsu, Peoples R China
[3] China Pharmaceut Univ, Sch Sci, Nanjing 210009, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
OPC-108459; ONO-4232; GSK-2798745; LIK-066; TAK-536TCH; bococizumab; SUBTILISIN/KEXIN TYPE 9; 1ST CLINICAL-EXPERIENCE; ARRESTIN-BIASED LIGAND; II TYPE-1 RECEPTOR; HEART-FAILURE; HEALTHY-VOLUNTEERS; CHOLESTEROL EFFLUX; SODIUM-NITRITE; MONOCLONAL-ANTIBODY; APOA-IMILANO/POPC;
D O I
10.3390/ijms20184513
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cardiovascular drug research and development (R&D) has been in active state and continuously attracts attention from the pharmaceutical industry. However, only one individual drug can eventually reach the market from about the 10,000 compounds tested. It would be useful to learn from these failures when developing better strategies for the future. Discontinued drugs were identified from a search performed by Thomson Reuters Integrity. Additional information was sought through PubMed, ClinicalTrials.gov, and pharmaceutical companies search. Twelve compounds discontinued for cardiovascular disease treatment after reaching Phase I-III clinical trials from 2016 to 2018 are detailed in this manuscript, and the reasons for these failures are reported. Of these, six candidates (MDCO-216, TRV027, ubenimex, sodium nitrite, losmapimod, and bococizumab) were dropped for lack of clinical efficacy, the other six for strategic or unspecified reasons. In total, three candidates were discontinued in Phase I trials, six in Phase II, and three in Phase III. It was reported that the success rate of drug R&D utilizing selection biomarkers is higher. Four candidate developments (OPC-108459, ONO-4232, GSK-2798745, and TAK-536TCH) were run without biomarkers, which could be used as surrogate endpoints in the 12 cardiovascular drugs discontinued from 2016 to 2018. This review will be useful for those involved in the field of drug discovery and development, and for those interested in the treatment of cardiovascular disease.
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页数:18
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