A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes
- 19 February 2020
- journal article
- research article
- Published by Wiley in Diabetes, Obesity and Metabolism
- Vol. 22 (7), 1111-1121
- https://doi.org/10.1111/dom.14010
Abstract
Aims 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. Material and Methods 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. Results 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. Conclusions 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 publication has 20 references indexed in Scilit:
- Disease-Modifying Therapies in Type 1 Diabetes: A Look into the Future of Diabetes PracticeDrugs, 2019
- A new therapeutic approach for type 1 diabetes: Rationale for GNbAC1, an anti‐HERV‐W‐Env monoclonal antibodyDiabetes, Obesity and Metabolism, 2018
- An ancestral retroviral protein identified as a therapeutic target in type-1 diabetesJCI Insight, 2017
- Type 1 diabetes pathogenesis is modulated by spontaneous autoimmune responses to endogenous retrovirus antigens in NOD miceEuropean Journal of Immunology, 2017
- Strategies for clinical trials in type 1 diabetesJournal of Autoimmunity, 2016
- First international workshop on human endogenous retroviruses and diseases, HERVs & disease 2015Mobile DNA, 2015
- T cells in type 1 diabetes: Instructors, regulators and effectors: A comprehensive reviewJournal of Autoimmunity, 2015
- Toll like receptors and pancreatic diseases: From a pathogenetic mechanism to a therapeutic targetCancer Treatment Reviews, 2015
- Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env proteinmAbs, 2015
- The Envelope Protein of a Human Endogenous Retrovirus-W Family Activates Innate Immunity through CD14/TLR4 and Promotes Th1-Like ResponsesThe Journal of Immunology, 2006