TY - JOUR
T1 - Dusquetide
T2 - A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study
AU - Kudrimoti, Mahesh
AU - Curtis, Amarintha
AU - Azawi, Samar
AU - Worden, Francis
AU - Katz, Sanford
AU - Adkins, Douglas
AU - Bonomi, Marcelo
AU - Elder, Jenna
AU - Sonis, Stephen T.
AU - Straube, Richard
AU - Donini, Oreola
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2016/12/10
Y1 - 2016/12/10
N2 - Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.
AB - Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.
KW - Cancer supportive care
KW - Dusquetide
KW - Head and neck cancer
KW - Immune
KW - Innate
KW - Oral mucositis
UR - http://www.scopus.com/inward/record.url?scp=84992047277&partnerID=8YFLogxK
U2 - 10.1016/j.jbiotec.2016.10.010
DO - 10.1016/j.jbiotec.2016.10.010
M3 - Article
C2 - 27746305
AN - SCOPUS:84992047277
SN - 0168-1656
VL - 239
SP - 115
EP - 125
JO - Journal of Biotechnology
JF - Journal of Biotechnology
ER -