Silevimig matches human rabies immunoglobulin in phase III trial
Primary endpointAdjusted geometric mean concentration (GMC) of rabies virus-neutralizing antibodies (RVNAs) on day 7, the proportion of participants with an RVNA level of ≥ 0.5 IU/mL (seroresponse) by day 14, and the rabies-free survival rate in 1 year (D365)
Where these numbers come from
“On day 7, the adjusted GMC of RVNAs was 0.40 IU/mL in the Silevimig group versus 0.36 IU/mL in the HRIG group, meeting the non-inferiority criterion (ratio 1.11; 95% CI: 1.01-1.21).”
The publication
In a phase III trial of 1,200 adults with suspected WHO category III rabies exposure, silevimig was non-inferior to human rabies immunoglobulin (HRIG) for post-exposure prophylaxis. The adjusted geometric mean concentration of rabies virus-neutralizing antibodies on day 7 was 0.40 IU/mL for silevimig versus 0.36 IU/mL for HRIG, with a ratio of 1.11 (95% CI: 1.01-1.21).
Who the findings apply to
The study enrolled adults older than 18 years with suspected WHO category III rabies exposure.
Participants were randomly assigned in a 3:1 ratio to receive either silevimig or HRIG.
After wound cleansing, the study drug was administered on day 0, together with a rabies vaccine given on days 0, 3, 7, 14, and 28.
Why this matters
Rabies post-exposure prophylaxis requires immediate passive immunization to bridge the gap until active vaccine-induced immunity develops. This trial demonstrates that silevimig, a bispecific monoclonal antibody, can replace HRIG, which is often scarce and expensive, without compromising early antibody responses or safety.
What the study found
On day 7, the adjusted geometric mean concentration of rabies virus-neutralizing antibodies was 0.40 IU/mL in the silevimig group versus 0.36 IU/mL in the HRIG group.
The non-inferiority criterion was met with a ratio of 1.11 and a 95% confidence interval of 1.01-1.21.
Seroresponse rates on days 14 and 90 were slightly higher with silevimig.
No rabies cases occurred during the one-year follow-up, resulting in a 100% rabies-free survival rate in both groups.
What the result does not establish
The trial was conducted in adults with suspected WHO category III exposure, so results may not apply to other exposure categories or age groups.
Most adverse events were mild to moderate, but the study did not report specific rates of serious adverse events in the abstract.
The evidence is based on a single phase III trial with a 1-year follow-up period.
Authors’ conclusion
“Silevimig was non-inferior to HRIG in inducing early RVNA responses, was well tolerated, and did not interfere with vaccine-induced immunity. These findings support Silevimig as a safe and effective alternative for passive rabies post-exposure prophylaxis (ClinicalTrials, NCT05846568).”
Study and sources
Comparison of Silevimig, a Novel Bispecific Anti-Rabies Monoclonal Antibody, with Human Rabies Immunoglobulin for Post-Exposure Prophylaxis: A Phase III, Randomized, Double-Blind, Non-Inferiority Trial
Randomised trial · Phase 3 · Clinical infectious diseases · 2026-09-21
Sources and limitations
- PubMed record PMID 42764163 (PubMed / NLM · 2026-09-21)
- Trial registry NCT05846568 (ClinicalTrials.gov · 2026-09-21)
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