Imperial College London
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Professor Kausik Ray

Faculty of Medicine, School of Public Health

Chair in Public Health (Clinical)
 
 
 
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Contact

 

+44 (0)20 7594 0716k.ray

 
 
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Assistant

 

Mrs Jennifer Landmann +44 (0)20 7594 9602

 
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Location

 

320Reynolds BuildingCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Landmesser:2021:cvr/cvaa077,
author = {Landmesser, U and Haghikia, A and Leiter, LA and Wright, RS and Kallend, D and Wijngaard, P and Stoekenbroek, R and Kastelein, JJP and Ray, KK},
doi = {cvr/cvaa077},
journal = {Cardiovascular Research},
pages = {284--291},
title = {Effect of inclisiran, the siRNA against PCSK9, on platelets, immune cells and immunological biomarkers - a pre-specified analysis from ORION-1},
url = {http://dx.doi.org/10.1093/cvr/cvaa077},
volume = {117},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - INTRODUCTION: siRNA-based targeting of PCSK9 represents a novel therapeutic approach that may provide a convenient, infrequent and safe dosing schedule to robustly lower LDL-C. Given the long duration of action, however, establishing safety in particular with respect to immunogenicity is of paramount importance. In earlier clinical studies of other RNA-targeted treatment approaches (antisense oligonucleotide therapy) immunological and haematological adverse-effects, in particular thrombocytopenia and pro-inflammatory effects, have been reported. Here, we present the pre-specified safety analysis from ORION-1 evaluating platelets, immune cells, immunological markers, antidrug antibodies and clinical immunogenicity adverse events under PCSK9 siRNA treatment with inclisiran. METHODS AND RESULTS: The pre-specified safety analysis from ORION-1 was performed in 6 different inclisiran dosing regimens in patients at high risk of cardiovascular disease with elevated LDL-C levels. Patients received either a single-dose (SD: 200mg, n = 60; 300mg, n = 62 or 500mg, n = 66) or double-dose starting regimen (DD: 100mg, n = 62; 200mg, n = 63; or 300mg, n = 61 on days 1 and 90) of inclisiran or placebo (single-dose: n = 65; double-dose: n = 62). The effects of inclisiran on haematological parameters including platelet counts, lymphocytes and monocytes as well as on the immune markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were examined after 180 days. Immunogenicity was further evaluated by analysis of anti-drug-antibodies (ADA) towards inclisiran in 6068 study samples and by careful analysis of immunogenicity adverse events as part of the pharmacovigilance strategy.At day 180 no significant alterations of platelet counts were observed in any of the dosing groups (change from baseline, single dose: 200mg: 0.8%; 300mg: -0.5%; 500mg: -1.8%; double
AU  - Landmesser,U
AU  - Haghikia,A
AU  - Leiter,LA
AU  - Wright,RS
AU  - Kallend,D
AU  - Wijngaard,P
AU  - Stoekenbroek,R
AU  - Kastelein,JJP
AU  - Ray,KK
DO  - cvr/cvaa077
EP  - 291
PY  - 2021///
SN  - 0008-6363
SP  - 284
TI  - Effect of inclisiran, the siRNA against PCSK9, on platelets, immune cells and immunological biomarkers - a pre-specified analysis from ORION-1
T2  - Cardiovascular Research
UR  - http://dx.doi.org/10.1093/cvr/cvaa077
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32243492
UR  - https://academic.oup.com/cardiovascres/article/doi/10.1093/cvr/cvaa077/5815561
UR  - http://hdl.handle.net/10044/1/78216
VL  - 117
ER  -
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