Ebola future or investigational therapies

Jump to navigation Jump to search

Ebola Microchapters


Patient Information


Historical Perspective




Differentiating Ebola from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


Algorithm for the Evaluation of the Returned Traveler

Emergency Department Evaluation

Case Definition

History and Symptoms

Physical Examination

Laboratory Findings

Other Diagnostic Studies


Medical Therapy

Hospital Preparedness


Air Medical Transport

Monitoring and Movement Following Exposure

Primary Prevention

Future or Investigational Therapies

Postmortem Care

Postmortem Care

Case Studies

Case #1

Ebola future or investigational therapies On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Ebola future or investigational therapies

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Ebola future or investigational therapies

CDC on Ebola future or investigational therapies

Ebola future or investigational therapies in the news

Blogs on Ebola future or investigational therapies

Directions to Hospitals Treating ebola

Risk calculators and risk factors for Ebola future or investigational therapies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Serge Korjian M.D.; Ahmed Younes M.B.B.CH [2]


There are no current antiviral therapies or vaccines for Ebola. Promising results from pre-clinical studies on agents such as ZMapp, AV6001, and TKM-Ebola have led to the development of phase I trials to evaluate the safety of these agents for human use. In August 2014, all Ebola-targeting therapies were granted fast-track designation by the FDA given the expanding outbreak.

Investigational Therapies


  • Favipiravir, approved in Japan for stockpiling against influenza pandemics, appears to be useful in a mouse model of Ebola.[1] On 4 October 2014, it was reported that a French nun who contracted Ebola while volunteering in Liberia was cured with Favipiravir treatment.[2]
  • Brincidofovir is a broad-spectrum antiviral drug. Its maker has been granted FDA approval to proceed with a trial to test its safety and efficacy in Ebola patients.[3] It has been used to treat the first patient diagnosed with Ebola in the USA, after he had recently returned from Liberia.[4][5]
  • Lamivudine, usually used to treat HIV / AIDS, was reported in September 2014 to have been used successfully to treat 13 out of 15 Ebola-infected patients by a doctor in Liberia, as part of a combination therapy also involving intravenous fluids and antibiotics to combat opportunistic bacterial infection of Ebola-compromised internal organs.[6] Western virologists have however expressed caution about the results, due to the small number of patients treated and confounding factors present. Researchers at the NIH stated that lamivudine had so far failed to demonstrate anti-Ebola activity in preliminary in vitro tests, but that they would continue to test it under different conditions and would progress it to trials if even slight evidence for efficacy is found.[7]


ZMapp is an experimental drug composed of 3 humanized monoclonal antibodies currently being investigated for the treatment of Ebola virus disease. The component monoclonal antibodies are recombinantly manufactured in a variety of tobacco (Nicotiana benthamiana). It has not yet been tested in humans for safety or effectiveness. Zmapp was studied in a preclinical study involving rhesus macaques exposed to the virus. The drug was successful in rescuing 100% (21/21) of the macaques when the treatment was initiated within 5 days of the Ebola exposure. High grade fever, and significant viremia was present in many animals before the intervention. Full recovery was also observed in animals with advanced disease with elevated liver enzymes, mucosal hemorrhages and generalized petechia. ZMapp was also found to be cross-reactive with the Guinean variant of Ebola. [8]


AVI-6002 is an investigational drug consisting of positively charged phosphorodiamidate morpholino oligomers (PMOplus). AVI-6002 is a form of antisense therapy whereby a particular gene can be silenced by synthesizing a strand of nucleic acid (DNA, RNA or a chemical analogue) that will bind the messenger RNA (mRNA) produced by that gene. Pre-clinical studies demonstrated that AVI-6002 administered intravenously within 30-60 min of exposure to the virus protects approximately 60% of rhesus monkeys against the Zaire Ebola virus (ZEBOV).[9] A phase I trial that involved 30 healthy volunteers enrolled in six-dose escalation cohorts demonstrated good safety and tolerability of AVI-6002.[10]


TKM-Ebola is an LNP-siRNA (lipid nanoparticle-small interfering RNA). Small interfering RNAs are a class of double-stranded RNA molecules that interfere with gene expression by causing breakdown of mRNA. TKM-Ebola is a combination of siRNAs 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). A proof of concept study that included monkeys and macaques demonstrated approximately full protection from the virus when the drug was given 30 minutes post-exposure and repeat dosing was administered daily over the next 6 days.[11] In January 2014, a phase I clinical trial evaluating TKM-Ebola in healthy volunteers was announced. Although the study was initially put on hold due to significant flu-like symptoms, the FDA modified this to a partial clinical hold. This action enables the potential use of TKM-Ebola in individuals infected with Ebola virus.[12]

Prevention of Ebola virus diease

rVSV-ZEBOV vaccine

  • The study utilized a“ring vaccination” design whereby each case contact (household contacts, workmates, visitors, etc) for 3 weeks prior to the onset of symptoms was followed and their network was mapped to form a "cluster". A total of 117 clusters were identified; each one consisted of approximately 80 individuals. Subjects (contacts of the infected individual) were randomized either to receive the vaccine immediately or 3 weeks after the start of the trial. The vaccine was given to those who are above 18 years of age.
  • After 10 days, none of the participants in the vaccinated group developed hemorrhagic fever. At the same time, 23 cases of Ebola virus infection were confirmed in the delayed vaccine group (who had not yet been immunized).
  • The vaccine is not fully approved yet, however, it can be available prior to approval during an outbreak through a “compassionate use" approval, meaning that it can be administered after signing an informed consent.
  • In light of the recent outbreak in the Democratic Republic of Congo[15], high hopes are held upon the "compassionate use" of rVSV-ZEBOV to limit the impact of the outbreak.


{{#ev:youtube|IrVteqtTPgE}} {{#ev:youtube|9MTqtORMaJQ}}

Other vaccines under experimentation



  1. Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S (2014). "Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model". Antiviral Res. 105: 17–21. doi:10.1016/j.antiviral.2014.02.014. PMID 24583123.
  2. "French nurse cured of Ebola contracted in Liberia". MSN. Retrieved 7 October 2014.
  3. "Chimerix gets FDA approval to test drug for Ebola". Associated Press. 17 October 2014.
  4. "Chimerix Announces Emergency Investigational New Drug Applications for Brincidofovir Authorized by FDA for Patients With Ebola Virus Disease". Retrieved 7 October 2014.
  5. Perrone, Matthew (6 October 2014). "Experimental Drug Provided to Dallas Ebola Patient". ABC. AP. Retrieved 6 October 2014.
  6. "Doctor treats Ebola with HIV drug in Liberia -- seemingly successfully. Elizabeth Cohen, CNN news. 29 September 2014". CNN. 27 September 2014. Retrieved 7 October 2014.
  7. "A Liberian doctor is using HIV drugs to treat Ebola victims. The NIH is intrigued. Elahe Izadi, Washington Post. 2 October 2014". Washington Post. Retrieved 7 October 2014.
  8. Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB; et al. (2014). "Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp". Nature. 514 (7520): 47–53. doi:10.1038/nature13777. PMID 25171469.
  9. Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS, Van Tongeren SA; et al. (2010). "Advanced antisense therapies for postexposure protection against lethal filovirus infections". Nat Med. 16 (9): 991–4. doi:10.1038/nm.2202. PMID 20729866.
  10. Heald AE, Iversen PL, Saoud JB, Sazani P, Charleston JS, Axtelle T; et al. (2014). "Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single Ascending Dose Studies". Antimicrob Agents Chemother. doi:10.1128/AAC.03442-14. PMID 25155593.
  11. Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V; et al. (2010). "Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study". Lancet. 375 (9729): 1896–905. doi:10.1016/S0140-6736(10)60357-1. PMID 20511019.
  12. [| About Investigational TKM-Ebola Therapeutic. Tekmira Pharmaceuticals Corporation.]
  13. Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Diatta I, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Watle SV, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine MM, Mandal S, Mauget T, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Røttingen JA, Kieny MP (2017). "Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!)". Lancet. 389 (10068): 505–518. doi:10.1016/S0140-6736(16)32621-6. PMC 5364328. PMID 28017403.
  14. "WHO | Final trial results confirm Ebola vaccine provides high protection against disease".
  15. "Congo reports death in new Ebola virus "outbreak" - CBS News".
  16. "Open-Label Study of INO-4212 With or Without INO-9012, Administered IM or ID Followed by Electroporation in Healthy Volunteers - Tabular View - ClinicalTrials.gov".
  17. "Ebola Immunotherapy".

Template:WH Template:WS