Antirabies Monoclonal Antibody Cocktail Noninferior to Human Rabies Immunoglobulin

By Reuters Staff

July 27, 2020

NEW YORK (Reuters Health) - An anti-rabies monoclonal antibody cocktail is as effective as human rabies immunoglobulin (HRIG) at providing rabies-virus-neutralizing antibodies, researchers in India report.

The World Health Organization (WHO) recommends rabies vaccine and rabies immunoglobulins for category III rabies exposures (single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal licks, and exposures due to direct contact with bats).

While there is no "protective" immunoglobulin titer against rabies virus, complete neutralization of rabies virus at a serum dilution of 1:5 (approximately 0.11 IU/mL) is recommended by the U.S. Advisory Committee on Immunization Practices as evidence as evidence of neutralizing antibodies. Previous clinical studies have found that titers of rabies-virus-neutralizing antibody range between about 6 and 12 IU/mL among healthy individuals completing the rabies vaccination series.

Dr. Kevinkumar Kansagra from Cadila Healthcare Limited, in Ahmedabad, Gujarat, India, and colleagues compared the effectiveness of an anti-rabies monoclonal antibody cocktail (Twinrab, containing two antibodies: docaravimab and miromavimab) versus HRIG in a phase-3, randomized, open-label, noninferiority trial of 308 patients with category III exposure to a suspected rabid animal.

All patients received 5 doses of rabies vaccine (on days 0, 3, 7, 14 and 28), and 154 patients each were assigned to receive Twinrab or HRIG.

The proportion of patients in the per-protocol population with neutralizing antibody titers of at least 0.5 IU/mL on day 14, the primary endpoint of the study, was 90.21% (129/144) in the Twinrab group and 94.37% (134/142) in the HRIG group, a difference that satisfied the noninferiority criteria.

The geometric mean titer on day 14 was 2.90 IU/mL in the Twinrab group versus 3.59 IU/mL in the HRIG group in the per-protocol population, the researchers report in Clinical Infectious Diseases.

On days 28, 42 and 84, the geometric mean titers were 7.38, 9.88 and 3.14 IU/mL, respectively, in the Twinrab group and 7.23, 7.78 and 2.65 IU/mL, respectively, in the HRIG group.

The occurrence of local reactions was not significantly different in the Twinrab (27.70%) and HRIG (21.19%) groups (P=0.1901). There were no deaths or serious adverse events during the study.

“The development of Twinrab would ensure a safe and cost-effective solution to the supply of a life-saving biological to the developing and under-developed rabies-endemic countries without any supply limitations thereby, eventually saving many lives,” the authors conclude.

Twinrab was approved by the Drug Controller General of India in September 2019 for rabies postexposure prophylaxis (in combination with rabies vaccine), and the U.S. Food and Drug Administration has granted it orphan-drug status.

Dr. Kansagra did not respond to a request for comments.

Cadila Healthcare employed several of the authors, who also have a related patent pending.

SOURCE: Clinical Infectious Diseases, online June 17, 2020.