TKM-Ebola

Experimental antiviral drug for Ebola disease that failed

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 proteins, TKM-Ebola inhibits virus replication and eliminates 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 it was isolated from several Ebola virus families and the specific genomic sequence was determined. The company re-designed TKM-Ebola and renamed it 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 treatments. The FDA placed 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 changing its name to Arbutus, suspending development of the drug for Ebola and changing its focus to developing treatments for hepatitis B virus.[10]

## See also[edit]

* Atoltivimab/maftivimab/odesivimab, treatment of Zaire ebolavirus (Ebola virus)
* Favipiravir
* ZMapp

## References[edit]

1. ^ "Tekmira Pharma is Now Arbutus Biopharma (ABUS)". Street Insider. 3 August 2015. Retrieved 16 May 2016.
2. ^ a b c David Kroll for Forbes. 7 August 2014 FDA Moves On Tekmira's Ebola Drug While Sarepta's Sits Unused
3. ^ a b "TKM-Ebola". BioCentury. BioCentury Publications Inc. Retrieved 1 August 2015.
4. ^ 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): 362–65. Bibcode:2015Natur.521..362T. doi:10.1038/nature14442. PMC 4467030. PMID 25901685.
5. ^ "Tekmira Provides Periodic Update on TKM-Ebola Program (NASDAQ:ABUS)". investor.arbutusbio.com. Archived from the original on 8 December 2015. Retrieved 30 November 2015.
6. ^ Cynthia Koons, Caroline Chen and Robert Langreth for Bloomberg News. Aug 8, 2014 Ebola Drug by Tekmira May Be Used on Infected Patients
7. ^ "FDA modifies partial clinical hold on Tekmira Ebola study". Reuters. 10 April 2015. Retrieved 1 August 2015.
8. ^ Kupferschmidt, Kai (11 March 2015). "New Ebola drug trial starts in Sierra Leone". Science Magazine. AAAS. Retrieved 1 August 2015.
9. ^ Vogel, Gretchen; Kupferschmidt, Kai (19 June 2015). "In setback for potential Ebola drug, company halts trial". news.sciencemag.org. Retrieved 24 June 2015.
10. ^ Lisa Schnirring for CIDRAP News. Jul 20, 2015 Experimental Ebola drug shelved; study explores virus clearance

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