'''TKM-Ebola''' was an experimental [[antiviral drug]] for [[Ebola disease]] that was developed by Arbutus Biopharma (formerly Tekmira Pharmaceuticals Corp.)<ref>{{cite web | url =http://www.streetinsider.com/Corporate+News/Tekmira+Pharma+is+Now+Arbutus+Biopharma+%28ABUS%29/10771627.html | title =Tekmira Pharma is Now Arbutus Biopharma (ABUS) | date = August 3, 2015 | website = Street Insider | access-date = May 16, 2016}}</ref> in Vancouver, Canada.<ref name=Kroll/> The drug candidate was formerly known as Ebola-SNALP.<ref name=BCMIQ>{{cite web|title=TKM-Ebola|url=http://www.biocentury.com/products/tkm-ebola|website=BioCentury|publisher=BioCentury Publications Inc.|accessdate=1 August 2015}}</ref>
'''TKM-Ebola''' was an experimental [[antiviral drug]] for [[Ebola disease]] that was developed by Arbutus Biopharma (formerly Tekmira Pharmaceuticals Corp.)<ref>{{cite web | url =http://www.streetinsider.com/Corporate+News/Tekmira+Pharma+is+Now+Arbutus+Biopharma+%28ABUS%29/10771627.html | title =Tekmira Pharma is Now Arbutus Biopharma (ABUS) | date = August 3, 2015 | website = Street Insider | access-date = May 16, 2016}}</ref> in Vancouver, Canada.<ref name=Kroll/> The drug candidate was formerly known as Ebola-SNALP.<ref name=BCMIQ>{{cite web|title=TKM-Ebola|url=http://www.biocentury.com/products/tkm-ebola|website=BioCentury|publisher=BioCentury Publications Inc.|accessdate=1 August 2015}}</ref>
*[[File:RNAi-simplified.png|thumb|left|Mechanism of RNAi]][[Brincidofovir]]
TKM-Ebola is a combination of [[small interfering RNA]]s 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).<ref name="Kroll">David Kroll for Forbes. August 7, 2014 [http://www.forbes.com/sites/davidkroll/2014/08/07/fda-moves-on-tekmiras-ebola-drug-while-sareptas-sits-unused/ FDA Moves On Tekmira's Ebola Drug While Sarepta's Sits Unused]</ref><ref name="BCMIQ" /> By down-regulating these three protein, TKM-Ebola inhibit virus replication that eliminate the infection. The drug was effective in rhesus monkeys infected with Ebola.<ref>{{cite journal|last1=Thi|first1=Emily P.|last2=Mire|first2=Chad E.|last3=Lee|first3=Amy C. H.|last4=Geisbert|first4=Joan B.|last5=Zhou|first5=Joy Z.|last6=Agans|first6=Krystle N.|last7=Snead|first7=Nicholas M.|last8=Deer|first8=Daniel J.|last9=Barnard|first9=Trisha R.|last10=Fenton|first10=Karla A.|last11=MacLachlan|first11=Ian|last12=Geisbert|first12=Thomas W.|title=Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates|journal=Nature|date=22 April 2015|volume=521|issue=7552|pages=362–365|doi=10.1038/nature14442}}</ref> 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".<ref>{{Cite web|title = Tekmira Provides Periodic Update on TKM-Ebola Program (NASDAQ:ABUS)|url = http://investor.arbutusbio.com/releasedetail.cfm?ReleaseID=877397|website = investor.arbutusbio.com|accessdate = 2015-11-30}}</ref>
TKM-Ebola is a combination of [[small interfering RNA]]s 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).<ref name="Kroll">David Kroll for Forbes. August 7, 2014 [http://www.forbes.com/sites/davidkroll/2014/08/07/fda-moves-on-tekmiras-ebola-drug-while-sareptas-sits-unused/ FDA Moves On Tekmira's Ebola Drug While Sarepta's Sits Unused]</ref><ref name="BCMIQ" /> By down-regulating these three protein, TKM-Ebola inhibit virus replication that eliminate the infection. The drug was effective in rhesus monkeys infected with Ebola.<ref>{{cite journal|last1=Thi|first1=Emily P.|last2=Mire|first2=Chad E.|last3=Lee|first3=Amy C. H.|last4=Geisbert|first4=Joan B.|last5=Zhou|first5=Joy Z.|last6=Agans|first6=Krystle N.|last7=Snead|first7=Nicholas M.|last8=Deer|first8=Daniel J.|last9=Barnard|first9=Trisha R.|last10=Fenton|first10=Karla A.|last11=MacLachlan|first11=Ian|last12=Geisbert|first12=Thomas W.|title=Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates|journal=Nature|date=22 April 2015|volume=521|issue=7552|pages=362–365|doi=10.1038/nature14442}}</ref> 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".<ref>{{Cite web|title = Tekmira Provides Periodic Update on TKM-Ebola Program (NASDAQ:ABUS)|url = http://investor.arbutusbio.com/releasedetail.cfm?ReleaseID=877397|website = investor.arbutusbio.com|accessdate = 2015-11-30}}</ref>
*[[File:RNAi-simplified.png|thumb|Mechanism of RNAi]][[Brincidofovir]]
*[[Favipiravir]]
*[[Favipiravir]]
*[[ZMapp]]
*[[ZMapp]]
Revision as of 23:26, 5 August 2016
Ebola virus
TKM-Ebola was an experimental antiviral drug for Ebola disease that was developed by Arbutus Biopharma (formerly Tekmira Pharmaceuticals Corp.)[1] in Vancouver, Canada.[2] The drug candidate was formerly known as Ebola-SNALP.[3]
TKM-Ebola 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).[2][3] By down-regulating 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.[2] 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.[8][9] In July 2015 the company announced it was suspending development of the drug, changing its name to Arbutus, and changing its focus to developing treatments for Hepatitis B virus.[10]
^ 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.
