TKM-Ebola is an experimental antiviral drug for Ebola disease being developed by Arbutus Biopharma (Former name: Tekmira Pharmaceuticals Corp.) in Vancouver, Canada.[1][2] It was formerly known as Ebola-SNALP.[3]
Ebola Pathenogensis path
TKM-Ebola is a RNAi based therapy for Ebola infection, a highly infectious and fatal disease. It is a combination of small interfering RNAs targeting three of the seven proteins in Ebola virus: Zaire Ebola L polymerase, Zaire Ebola membrane-associated protein (VP24), and Zaire Ebola polymerase complex protein (VP35).[1][3] By down-regulate these three protein, TKM-Ebola inhibit virus replication that eliminate the infection. The drug was effective in rhesus monkeys infected with Ebola.[4] After the Ebola outbreak in West Africa in 2014, the new variant responsible for was isolated from several Ebola virus family and the specific genomic sequence was determined. The company re-designed TKM-Ebola and termed as "TKM-Ebola-Guinea".[5]
In January 2014, Tekmira started a Phase I clinical trial of TKM-Ebola to assess its safety in healthy people with a dose of 0.24 mg/kg/day for seven day treatment. The FDA put the trial on clinical hold in July 2014 to assess results, after some subjects had flu-like responses.[6] In August, the FDA changed the status to "partial hold", allowing the drug to be used under Expanded access in people infected with Ebola but with the Phase I trial still suspended.[1] In April 2015 the FDA allowed the study to resume at a lower dose.[7]
A Phase II trial started on 11 March 2015 in Sierra Leone, West Africa and stopped enrolling new subjects on 19 June 2015 after it appeared not to work; statistical analysis was ongoing at the time.[8][9]
TKM-Ebola is under a $140 million contract with the U.S. Department of Defense. Phase II trial is funded by Welcome Trust's £3.2 million Ebola therapeutics platform.
^ ab"TKM-Ebola". BioCentury. BioCentury Publications Inc. Retrieved 1 August 2015.
^Thi, Emily P.; Mire, Chad E.; Lee, Amy C. H.; Geisbert, Joan B.; Zhou, Joy Z.; Agans, Krystle N.; Snead, Nicholas M.; Deer, Daniel J.; Barnard, Trisha R.; Fenton, Karla A.; MacLachlan, Ian; Geisbert, Thomas W. (22 April 2015). "Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates". Nature. 521 (7552): 362–365. doi:10.1038/nature14442.
