Title : SYN023 mAb cocktail for rabies prophylaxis
Abstract:
SYN023 is a mixture of two anti-rabies humanized monoclonal IgG1κ antibodies which bind to distinct and non-overlapping antigenic sites on the rabies virus glycoprotein. Updated spectrum of neutralization studies and epitope mapping analyses will be discussed. A Phase 2b and a Phase 3 randomized double-blinded trials were conducted to demonstrate the safety and efficacy of SYN023 in 1448 Category III rabies patients. The analysis of the safety profile of SYN023 based on the integrated data from all 6 clinical trials demonstrated that SYN023 was generally well tolerated when administered alone or with rabies vaccine in subjects with rabies exposure as well as healthy subjects and has a favorable safety profile. The safety profile was similar to that of the currently approved HRIG in the US. Overall, the incidence of serious TEAEs throughout the studies was low (<5.0%) and similar between the SYN023 and HRIG groups. No TEAE led to study withdrawal in subjects treated with SYN023. The most common solicited TEAEs with SYN023 and HRIG were injection site swelling, injection site pain, headache, and injection site erythema. A higher incidence of these TEAEs was noted in subjects treated with HRIG than in subjects treated with SYN023. Across 6 clinical trials, RVNA appeared to be adequate at the 0.3 mg/kg dose level to rapidly establish RVNA of ≥0.5 IU/mL in the rabies-exposed person. The primary endpoint for the ISE was the GMC of the RVNA on Study Day 8 in the FAS (SYN023, N=978; HRIG, N=469). The GMC ratio of RVNA (SYN023 vs HRIG) on Study Day 8 was 13.977 (97.5% CI: 11.887, infinity; P<0.0001); SYN023 was considered superior to HRIG with respect to GMC of RVNA on Study Day 8, as the lower bound of the 97.5% CI was above the prespecified margin 1.2. The immune response (RVNA ≥0.5 IU/mL) rate ratio (SYN023 vs HRIG) was 0.99 (95% CI: 0.96, 1.01; P<0.0001); SYN023 was considered noninferior to HRIG with respect to immune response rates on Study Day 99, as the lower bound of the 95% CI was above the prespecified margin 0.9. There were no deaths, serious adverse events, or AEs leading to study discontinuation up to 365 days after dosing.
