Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

TKM-130803 is a specific anti-EBOV therapeutic comprising of two small interfering RNAs (siRNA) siLpol-2 and siVP35-2. The pharmacokinetics (PK) of these siRNAs was defined in Ebola virus disease (EVD) patients. The relationship between PK and patient survival was explored. Plasma concentration of siRNA was compared to survival at 14 days for seven subjects with EVD in Sierra Leone who received 0.3 mg/kg of TKM-130803 by intravenous infusion over 2 hours daily for up to 7 days. PKdatawere fitted to two-compartment models then Monte Carlo simulated PK profiles were compared to ET (Cmax 0.04-0.57 ng/mL and mean concentration 1.43 ng/mL), and TT (3000 ng/mL). siRNA was in quantitative excess of virus genomes throughout treatment, but the 95% percentile exceeded TT. Plasma concentration of both siRNAs were higher in subjects who died compared to subjects who survived (p<0.025 both siRNAs).The maximum AUC for which the 95% percentile remained under TT was a continuous infusion of 0.15mg/kg/day. TKM-130803 was circulating at sufficient concentrations, considered needed for efficacy but given extremely high viral loads it seems likely that the patients died because they were physiologically beyond the point of no return. Subjects who died exhibited some indication of impaired drug clearance, justifying caution in dosing strategies for such patients. This analysis has given a useful insight into the pharmacokinetics of the siRNA in the disease state andillustrates the valueof designing PKPD studies into future clinical trials in epidemic situations.

Original publication




Journal article


Access Microbiology


Microbiology Society

Publication Date





vaccine related, infection, emerging infectious diseases, biodefense, prevention, clinical research, genetics