Temelimab safe even high dose

[frodo]

A High-dose Pharmacokinetic Study of a New IgG4 Monoclonal Antibody Temelimab/GNbAC1 Antagonist of an Endogenous Retroviral Protein pHERV-W Env

https://www.sciencedirect.com/science/a ... 02966#tbl2

Discussion

We report here the results of a PK study testing very high doses of the IgG4 mAb temelimab, the first mAb targeting an endogenous retroviral protein, pHERV-W Env, which is associated with MS and type 1 diabetes. Motivated by the need to increase the dose of temelimab in the CNS, the expected site of expression of the target in MS,5 this analysis is the third Phase I study with this mAb.

In this study, which tested single intravenous doses of temelimab up to 110 mg/kg in a single administration with high-speed infusion, the safety profile of temelimab remained favorable, as previously reported with lower doses.9, 10 The adverse events were essentially related to minor upper respiratory tract disorders and headache. There was no evidence of any specific events (including no infusion reactions or hypersensitivity) or any increase in frequency or severity of adverse events even at very high doses of temelimab.

Based on the data, one can conclude that a single intravenous administration of temelimab is well tolerated and safe in healthy subjects up to a dose of 110 mg/kg. This favorable safety profile, even at a very high dose, is probably associated with the high specificity of temelimab to a target with unknown physiological function. No antidrug antibodies were observed during treatment, which is supported by the current absence of immunogenicity observed thus far in other clinical trials.8, 9, 10, 11

The amount of temelimab used in the current study is among the highest dosages of mAb administered in clinical trials.