Temelimab, an IgG4 Anti-Human Endogenous Retrovirus Monoclonal Antibody: An Early Development Safety Review

Drug Saf. 2020 Dec;43(12):1287-1296. doi: 10.1007/s40264-020-00988-3.


Introduction: Temelimab (formerly called GNbAC1) is an immunoglobulin (Ig) G4 monoclonal antibody that targets the human endogenous retroviral envelope protein HERV-W-Env, shown to be associated with the pathogenesis of certain autoimmune disorders such as multiple sclerosis (MS) and type 1 diabetes mellitus (T1D). By neutralizing HERV-W-Env, temelimab could act as a disease-modifying therapy for these disorders. It is currently in clinical development for MS and T1D.

Methods: The safety information on temelimab (including potential infusion-related reactions, malignancies, pregnancies and antidrug antibodies) collected during three phase I and four phase II clinical trials was reviewed and is summarized in this article.

Results: In the entire development program, 54 healthy volunteers received single doses of temelimab in three phase I studies, and 334 MS or T1D patients received temelimab for a total estimated exposure of 465 patient-years in four phase II trials. No differences were observed between numbers of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) between treatment groups (including placebo), and the number of SAEs was limited. Furthermore, no differences were observed in laboratory evaluations, vital signs, electrocardiogram (ECG), or physical examinations between treatment groups. Rare potential infusion-related reactions were reported. Temelimab treatment was not associated with an increased risk of infections or infestations.

Conclusion: These results suggest that treatment with temelimab was not associated with any particular type of AE. Overall, temelimab was safe and very well tolerated over the tested dose range after repeated monthly administrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Gene Products, env / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Multiple Sclerosis / drug therapy*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Gene Products, env
  • Immunoglobulin G
  • temelimab