Clinical trials and post-marketing studies of anti-rabies monoclonal antibodies for post-exposure prevention: A review

INTRODUCTION. Rabies is an invariably fatal disease having no adequate cure; in some cases it requires administration of rabies immunoglobulin combined with rabies vaccine. Given the supply constraints of rabies immunoglobulin derived from donor blood, research is underway worldwide to develop preparations based on neutralising monoclonal antibodies (mAbs), which are potentially relevant for the Russian healthcare system.

AIM. This study aimed to perform a narrative review of the development, clinical trials, and post-marketing safety and efficacy studies of rabies monoclonal antibodies intended for post-exposure prophylaxis in combination with rabies vaccination.

DISCUSSION. Currently, three rabies mAb drugs have been registered worldwide. Of them, two are manufactured in India (a recombinant human anti-rabies antibody; a combination drug of docaravimab and miromavimab) and one in China (ormutivimab). Preclinical studies of these drugs have confirmed their ability to neutralise the rabies virus, including wild strains. Clinical trials have established a favourable safety profile for these anti-rabies mAbs (adverse events are generally transient and self-resolving) and a lack of immune interference with administered rabies vaccines. Administration of all the above drugs did not change immune response to the complete course of anti-rabies vaccination, unlike human immunoglobulin preparations. On Day 42 (4 weeks after the last dose of rabies vaccine), virus-neutralising antibody titers reached 31.12 IU/mL for the recombinant human rabies antibody preparation and 122 IU/mL for docaravimab and miromavimab combination. Controlled clinical trials and post-registration studies of the recombinant human rabies antibody and docaravimab-miromavimab combination showed no rabies episodes in patients receiving post-exposure prophylaxis with the study drugs and the rabies vaccine.

CONCLUSIONS. Anti-rabies mAb preparations are an effective and safe option for post-exposure rabies prophylaxis, confirmed by their worldwide use. Integrating these drugs into comprehensive patient care will help overcome the potential shortage of rabies immunoglobulins in the Russian Federation. When registering anti-rabies mAbs, key objectives are to assess cross-reactivity with human tissues ex vivo and confirm neutralising activity against viral isolates common in Russia and the neighbouring countries.

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