Tuberculosis, volume 111, pages 20-30
Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB)
Liu Yongge
1
,
MATSUMOTO MAKOTO
2
,
Ishida Hidekaza
3
,
OHGURO Kinue
3
,
Yoshitake Masuhiro
1
,
Gupta Rajesh
1
,
Geiter Lawrence
1
,
Hafkin Jeffrey
1
1
Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA.
|
2
Pharmaceutical Business Division, Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan.
|
3
Department of Medical Innovations, New Drug Research Division, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan
|
Publication type: Journal Article
Publication date: 2018-07-01
Journal:
Tuberculosis
Quartile SCImago
Q2
Quartile WOS
Q3
Impact factor: 3.2
ISSN: 14729792, 1873281X
Microbiology (medical)
Microbiology
Infectious Diseases
Immunology
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is the leading cause of death from an infectious disease globally. The widespread and ever-increasing resistance to TB drugs is reducing the effectiveness of treatment and jeopardizing TB control. New effective drugs with acceptable safety profiles are needed to turn the tide. Since the early 1990s, Otsuka Pharmaceutical Co., Ltd. has had a TB drug development program that resulted in the selection and development of delamanid (OPC-67683, Deltyba®), a first-in-class bicyclic nitroimidazole. Delamanid was initially approved by the European Medicines Agency (EMA) in 2014 for the treatment of adult pulmonary multi-drug resistant (MDR)-TB when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. It has since been approved by several other countries/regions. In this review, we describe the history of delamanid's development, including the screening process, in vitro and in vivo characterization, as well as various clinical studies. Delamanid possesses potent activity against replicating, dormant, and intracellular MTB bacilli, and is bactericidal in mouse and guinea pig TB models. Delamanid resistance mechanisms have been attributed to genes in the F420-dependent deazaflavin nitroreductase bio-activation pathway, found in mycobacterium species but not in common bacterial or mammalian cells. Published susceptibility testing results from 744 clinical isolates from delamanid-naïve patients indicate that the natural resistance rate to delamanid is very low (1.3%). Delamanid is largely metabolized by albumin in serum, and to a much less extent by cytochrome P450 enzymes. Furthermore, it neither inhibits nor induces P450 enzymes. In terms of efficacy, delamanid demonstrated activity in an early bactericidal activity trial in drug susceptible pulmonary TB patients and increased 2-month sputum culture conversion rates when added to an optimized background regimen in MDR-TB patients in a phase 2b global clinical trial. In addition, recent results outside clinical studies show favourable responses in highly resistant TB patients including extensively drug resistant (XDR)-TB when treated with delamanid-containing regimens in routine programmatic settings. The primary safety concern with delamanid is QTcF interval prolongation, although this observation has thus far not been associated with any clinical cardiac events. Overall, delamanid appears to be a well-tolerated and safe anti-TB drug when compared to other drugs used to treat MDR-TB.
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1 publication, 1.02%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Cite this
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RIS |
BibTex
Cite this
GOST
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Liu Y. et al. Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB) // Tuberculosis. 2018. Vol. 111. pp. 20-30.
GOST all authors (up to 50)
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Liu Y., MATSUMOTO M., Ishida H., OHGURO K., Yoshitake M., Gupta R., Geiter L., Hafkin J. Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB) // Tuberculosis. 2018. Vol. 111. pp. 20-30.
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TY - JOUR
DO - 10.1016/j.tube.2018.04.008
UR - https://doi.org/10.1016%2Fj.tube.2018.04.008
TI - Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB)
T2 - Tuberculosis
AU - Liu, Yongge
AU - MATSUMOTO, MAKOTO
AU - Ishida, Hidekaza
AU - OHGURO, Kinue
AU - Yoshitake, Masuhiro
AU - Gupta, Rajesh
AU - Geiter, Lawrence
AU - Hafkin, Jeffrey
PY - 2018
DA - 2018/07/01 00:00:00
PB - Elsevier
SP - 20-30
VL - 111
SN - 1472-9792
SN - 1873-281X
ER -
Cite this
BibTex
Copy
@article{2018_Liu,
author = {Yongge Liu and MAKOTO MATSUMOTO and Hidekaza Ishida and Kinue OHGURO and Masuhiro Yoshitake and Rajesh Gupta and Lawrence Geiter and Jeffrey Hafkin},
title = {Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB)},
journal = {Tuberculosis},
year = {2018},
volume = {111},
publisher = {Elsevier},
month = {jul},
url = {https://doi.org/10.1016%2Fj.tube.2018.04.008},
pages = {20--30},
doi = {10.1016/j.tube.2018.04.008}
}