Ebola future or investigational therapies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2]; Serge Korjian M.D.; Ahmed Younes M.B.B.CH [3]
Overview
Management of Ebola virus disease has changed substantially. There are now 2 FDA-approved therapies for infection caused by Orthoebolavirus zairense (Zaire ebolavirus): ansuvimab (Ebanga) and Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn).[1][2] These therapies reduced 28-day mortality in the PALM randomized controlled trial and are recommended by the World Health Organization as first-line therapy for confirmed Zaire ebolavirus disease, in addition to aggressive supportive care.[3][4][5]
For prevention of Zaire ebolavirus disease, the field has also advanced substantially. Ervebo (rVSVΔG-ZEBOV-GP) is a licensed single-dose vaccine and remains the preferred vaccine for outbreak response and ring vaccination. A second licensed vaccine strategy, the 2-dose Zabdeno/Mvabea regimen (Ad26.ZEBOV followed by MVA-BN-Filo), is available in some jurisdictions and is better suited to preventive use than immediate outbreak response because of the prime-boost schedule.[6][7][8]
Most older “investigational therapies” on this page, including ZMapp, favipiravir, remdesivir, TKM-Ebola, AVI-6002, brincidofovir, and lamivudine, should no longer be presented as leading options for standard care of confirmed Zaire ebolavirus disease. Some retain research interest, but current treatment standards are dominated by monoclonal antibodies plus optimized supportive care.[9][10]
Investigational Therapies
Current preferred virus-specific therapies for Zaire ebolavirus
Ansuvimab (Ebanga)
- Ansuvimab is a human monoclonal antibody directed against the receptor-binding domain of the Zaire ebolavirus glycoprotein.[11]*
- It is FDA-approved for treatment of infection caused by Orthoebolavirus zairense in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Orthoebolavirus zairense infection.[1]*
- Among patients with lower viral load at presentation, mortality was substantially lower, underscoring the importance of early diagnosis and treatment.[3]*
- World Health Organization guidance recommends ansuvimab as a first-line therapy for confirmed Zaire ebolavirus disease.[5]*
Inmazeb (atoltivimab, maftivimab, odesivimab-ebgn; REGN-EB3)
- Inmazeb is a 3-monoclonal-antibody cocktail targeting distinct epitopes of the Zaire ebolavirus glycoprotein.[2]*
- It is FDA-approved for treatment of infection caused by Orthoebolavirus zairense in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for infection.[2]*
- In the PALM trial, 28-day mortality was 33.5% with Inmazeb versus 51.3% in the contemporaneous ZMapp comparison group.[3]*
- Inmazeb is also recommended by the World Health Organization as first-line therapy for confirmed Zaire ebolavirus disease.[5]*
PALM trial summary
The PALM trial established the modern therapeutic standard for Zaire ebolavirus disease. It enrolled 681 patients with RT-PCR-confirmed infection and compared ZMapp, remdesivir, ansuvimab (mAb114), and REGN-EB3 (Inmazeb).[3]
| Therapy | 28-day mortality | Current status |
|---|---|---|
| Ansuvimab (mAb114; Ebanga) | 35.1% | FDA-approved; preferred therapy |
| REGN-EB3 (Inmazeb) | 33.5% | FDA-approved; preferred therapy |
| ZMapp | 49.7% | No longer preferred |
| Remdesivir | 53.1% | Inferior in PALM; not recommended for routine Zaire ebolavirus treatment |
- Mortality was strongly related to baseline viral load: among patients with cycle-threshold values ≤22, mortality remained high even with effective monoclonal antibody therapy; among those with lower viral load, outcomes were much better.[3]*
- Each day of delay between symptom onset and enrollment was associated with an approximately 11% to 12% increase in the odds of death, reinforcing the need for early recognition and immediate treatment.[3]*
Older or nonpreferred antiviral therapies
| Therapy | Evidence summary | Current role |
|---|---|---|
| Remdesivir | Demonstrated preclinical activity against ebolaviruses and was evaluated in PALM, but was inferior to ansuvimab and Inmazeb with respect to mortality.[3] | Not recommended for routine Zaire ebolavirus treatment when preferred monoclonal antibodies are available; remains of research interest for combination therapy or viral persistence syndromes. |
| Favipiravir | Showed activity in animal models and was explored during the West Africa epidemic, but human data did not establish clear clinical efficacy. | Not a preferred or established antiviral therapy for confirmed Zaire ebolavirus disease. |
| ZMapp | Historically important and showed promising preclinical and early clinical data.[12] Inferior to ansuvimab and Inmazeb in PALM.[3] | No longer preferred. |
| Brincidofovir, lamivudine, TKM-Ebola, AVI-6002 | Part of the early wave of candidate therapies during the 2014-2016 epidemic, but none has become a current standard therapy for confirmed Zaire ebolavirus disease. | Historical or research relevance only; not current standard-of-care treatment. |
Broadly neutralizing and pan-ebolavirus monoclonal antibodies
- An important current research priority is development of therapies active beyond Zaire ebolavirus, particularly for Sudan virus and other orthoebolavirus species.*
- During the 2022 Sudan virus outbreak in Uganda, investigational use of MBP134, a broadly reactive monoclonal-antibody cocktail, occurred under monitored emergency use, but efficacy on survival cannot be inferred from those data.*
- No virus-specific therapy has yet achieved the same level of evidence and regulatory approval for Sudan virus disease as ansuvimab and Inmazeb have for Zaire ebolavirus.*
Prevention of Ebola virus disease
Licensed vaccines for Zaire ebolavirus
| Vaccine | Platform / schedule | Main use | Key evidence / status |
|---|---|---|---|
| Ervebo (rVSVΔG-ZEBOV-GP; rVSV-ZEBOV) | Recombinant, replication-competent vesicular stomatitis virus-vectored vaccine expressing the glycoprotein of Zaire ebolavirus; single-dose vaccine | Ring vaccination and rapid outbreak response for Zaire ebolavirus | FDA-approved for prevention of disease caused by Zaire ebolavirus; in the Guinea ring-vaccination trial, no cases occurred ≥10 days after randomization in the immediate-vaccination clusters.[6][13] |
| Zabdeno / Mvabea (Ad26.ZEBOV / MVA-BN-Filo) | 2-dose prime-boost regimen consisting of Ad26.ZEBOV followed approximately 8 weeks later by MVA-BN-Filo | Preventive vaccination for populations at ongoing but not imminent risk | Licensed in some jurisdictions and has World Health Organization prequalification status for prevention of disease due to Zaire ebolavirus; less suitable than Ervebo for immediate outbreak control because it requires two doses separated in time. |
- World Health Organization and global partners established a global stockpile of Ervebo in 2021 to support rapid, equitable outbreak response.[7]*
- From 2021 to 2023, 145,690 doses were shipped from the stockpile; most were used for preventive vaccination of high-risk groups, with a smaller fraction used for acute outbreak response.[7]*
- Ervebo remains the preferred vaccine for ring vaccination and rapid protection during outbreaks caused by Zaire ebolavirus.[7]*
- The PREVAC trial showed durable humoral responses with both rVSV-based and Ad26.ZEBOV/MVA-BN-Filo strategies, helping define longer-term vaccine strategies beyond emergency ring vaccination.*
Durability and revaccination considerations
- Important uncertainties remain regarding duration of protection and optimal revaccination strategies, particularly for frontline healthcare workers, children, survivors, and immunocompromised individuals.*
- Breakthrough infection in previously vaccinated individuals has been observed, indicating that protection is strong but not absolute and may wane over time.*
- There is not yet a clear global consensus on revaccination timing for all populations.*
Vaccines for Sudan virus and other non-Zaire ebolavirus species
There are currently no licensed vaccines for Sudan virus disease. The most clinically advanced Sudan virus-specific candidate is the single-dose cAd3-EBO S vaccine, which showed acceptable safety and immunogenicity in a phase 1 trial in healthy Ugandan adults.[8]
| Candidate | Target / platform | Current evidence |
|---|---|---|
| cAd3-EBO S | Sudan virus chimpanzee adenovirus vector vaccine | In a phase 1 trial, 34 of 40 participants (85%) had a Sudan virus glycoprotein-specific binding antibody response at 4 weeks, with durability in 31 of 38 participants (82%) up to 48 weeks.[8] |
| ChAdOx1 biEBOV | Bivalent Zaire ebolavirus/Sudan virus vector vaccine | Candidate vaccine under development. |
| VSV-SUDV | Sudan virus vesicular stomatitis virus-vector candidate | Candidate vaccine shortlisted for possible ring-vaccination evaluation during the 2022 Sudan virus outbreak. |
| Multivalent Ad26.Filo/MVA-BN-Filo approaches | Multivalent filovirus prime-boost strategies | Candidate strategies under development. |
| Replicon RNA vaccines | Earlier-stage RNA vaccine platform | Single-dose replicon RNA Sudan virus vaccine protected female guinea pigs in preclinical work.[14] |
- During the 2022 Sudan virus outbreak, World Health Organization advisors shortlisted 3 candidate vaccines for possible ring-vaccination evaluation: VSV-SUDV, ChAd3-SUDV, and biEBOV, but the outbreak was controlled before efficacy testing could proceed.*
Post-exposure prophylaxis and occupational exposure
- For high-risk exposure to Zaire ebolavirus, post-exposure approaches have included rapid vaccination with Ervebo and, increasingly, consideration of monoclonal antibodies because they provide immediate antiviral activity rather than requiring host immune priming.[11]*
- In a small prospective study of 23 high-risk exposed individuals, use of ansuvimab or REGN-EB3 as post-exposure prophylaxis was associated with no cases of Ebola virus disease, but these data are preliminary and not equivalent to randomized efficacy evidence.*
Historically important but outdated vaccine content
- The legacy statement that “there are no current antiviral therapies or vaccines for Ebola” is now incorrect and should be removed.*
- INO-4212 and other early DNA-vaccine programs are of historical interest, but they should not be foregrounded over currently licensed vaccines and clinically advanced candidates.*
- Older embedded videos and legacy outbreak-era text may be retained only if clearly identified as historical material and not presented as current standard guidance.*
References
- ↑ 1.0 1.1 "EBANGA (ansuvimab-zykl) prescribing information" (PDF). U.S. Food and Drug Administration. 2024. Retrieved May 27 2026. Check date values in:
|accessdate=(help) - ↑ 2.0 2.1 2.2 "INMAZEB (atoltivimab, maftivimab, and odesivimab-ebgn) prescribing information" (PDF). U.S. Food and Drug Administration. 2024. Retrieved May 27 2026. Check date values in:
|accessdate=(help) - ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Mulangu S, Dodd LE, Davey RT Jr, Tshiani Mbaya O, Proschan M, Mukadi D, Lusakibanza Manzo M, Nzolo D, Tshomba Oloma A, Ibanda A, Ali R, Coulibaly S, Levine AC, Grais R, Diaz J, Lane HC, Muyembe-Tamfum JJ (2019). "A randomized, controlled trial of Ebola virus disease therapeutics". N Engl J Med. 381 (24): 2293–2303. doi:10.1056/NEJMoa1910993. PMID 31774950.
- ↑ Rojek A, Fieggen J, Apiyo P, et al. (2025). "Ebola disease: bridging scientific discoveries and clinical application". Lancet Infect Dis. 25 (3): e165–e176. doi:10.1016/S1473-3099(24)00673-X. PMID 39675368 Check
|pmid=value (help). - ↑ 5.0 5.1 5.2 "WHO makes new recommendations for Ebola treatments, calls for improved access". World Health Organization. August 19 2022. Retrieved May 27 2026. Check date values in:
|accessdate=, |date=(help) - ↑ 6.0 6.1 "Ervebo". U.S. Food and Drug Administration. April 21 2026. Retrieved May 27 2026. Check date values in:
|accessdate=, |date=(help) - ↑ 7.0 7.1 7.2 7.3 Kallay R, Doshi RH, Muhoza P, Choi MJ, Legand A, Aberle-Grasse E, Bagayoko A, Hyde TB, Formenty P, Costa A (2024). "Use of Ebola vaccines - worldwide, 2021-2023". MMWR Morb Mortal Wkly Rep. 73 (16): 360–364. doi:10.15585/mmwr.mm7316a1. PMID 38662631 Check
|pmid=value (help). - ↑ 8.0 8.1 8.2 Mwesigwa B, Houser KV, Hofstetter AR, et al. (2023). "Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial". Lancet Infect Dis. 23 (12): 1408–1417. doi:10.1016/S1473-3099(23)00344-4. PMID 37544326 Check
|pmid=value (help). - ↑ Feldmann H, Sprecher A, Geisbert TW (2020). "Ebola". N Engl J Med. 382 (19): 1832–1842. doi:10.1056/NEJMra1901594. PMID 32286632 Check
|pmid=value (help). - ↑ Rigby I, Michelen M, Dagens A, et al. (2023). "Standard of care for viral haemorrhagic fevers (VHFs): a systematic review of clinical management guidelines for high-priority VHFs". Lancet Infect Dis. 23 (7): e240–e252. doi:10.1016/S1473-3099(22)00874-X. PMID 36758568 Check
|pmid=value (help). - ↑ 11.0 11.1 Moso MA, Lim CK, Williams E, et al. (2024). "Prevention and post-exposure management of occupational exposure to Ebola virus". Lancet Infect Dis. 24 (2): e93–e105. doi:10.1016/S1473-3099(23)00376-6. PMID 37722397 Check
|pmid=value (help). - ↑ Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP (2014). "Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp". Nature. 514 (7520): 47–53. doi:10.1038/nature13777. PMID 25171469.
- ↑ 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. PMID 28017403.
- ↑ O'Donnell KL, Anhalt H, Saturday G, et al. (2025). "Single-dose replicon RNA Sudan virus vaccine uniformly protects female guinea pigs from disease". Nat Commun. 16 (1): 4199. doi:10.1038/s41467-025-59560-1. PMID 40328820 Check
|pmid=value (help).