A Safety and Pharmacodynamics Study of Temelimab, an anti-HERV-W-Env Monoclonal Antibody, in Type 1 Diabetes Patients.

Abstract

Type 1 diabetes (T1D) is characterized by a loss of β-cell function resulting in insulin deficiency. The pathogenic human endogenous retrovirus type W envelope (pHERV-W-Env) protein is associated with T1D and may play a role in the loss of β-cells. Temelimab is a monoclonal antibody neutralizing pHERV-W-Env and we report its first study in T1D patients. This double blind placebo-controlled randomized clinical trial recruited adult T1D patients within 4 years post-diagnosis and remaining C-peptide secretion. Sixty four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24-week open-label extension during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess pharmacodynamics (PD) response such as C-peptide levels, insulin use, glycated hemoglobin (HbA1c), hypoglycemia and auto-antibodies. Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at Weeks 24 and 48. The frequency of hypoglycemia events was reduced with temelimab (p=0.0004) at Week 24 and the level of anti-insulin antibodies was lower with temelimab (p<0.01), the other auto-antibodies did not differ between groups. Temelimab appeared safe in T1D patients. Pharmacodynamics signals (hypoglycemia and anti-insulin antibodies) under temelimab were observed. Markers of β-cell functions were not modified by treatment. These results need to be further explored in younger T1D patients with earlier disease onset. This article is protected by copyright. All rights reserved.