Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study.

Abstract

BACKGROUND:

The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions.

OBJECTIVE AND METHODS:

This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24. Additional endpoints included numbers of T2 and T1-hypointense lesions, magnetization transfer ratio, and brain atrophy. In total, 270 participants were randomized to receive monthly intravenous temelimab (6, 12, or 18 mg/kg) or placebo for 24 weeks; at week 24 placebo-treated participants were re-randomized to treatment groups.

RESULTS:

The primary endpoint was not met. At week 48, participants treated with 18 mg/kg temelimab had fewer new T1-hypointense lesions (p = 0.014) and showed consistent, however statistically non-significant, reductions in brain atrophy and magnetization transfer ratio decrease, as compared with the placebo/comparator group. These latter two trends were sustained over 96 weeks. No safety issues emerged.

CONCLUSION:

Temelimab failed to show an effect on features of acute inflammation but demonstrated preliminary radiological signs of possible anti-neurodegenerative effects. Current data support the development of temelimab for progressive MS.

TRIAL REGISTRATION:

CHANGE-MS: ClinicalTrials.gov: NCT02782858, EudraCT: 2015-004059-29; ANGEL-MS: ClinicalTrials.gov: NCT03239860, EudraCT: 2016-004935-18.

• Authors: Hans-Peter Hartung, Tobias Derfuss, Bruce Ac Cree, Maria Pia Sormani, Krzysztof Selmaj, Jonathan Stutters, Ferran Prados, David MacManus, Hans-Martin Schneble, Estelle Lambert, Hervé Porchet, Robert Glanzman, David Warne, Francois Curtin, Gabrielle Kornmann, Bénédicte Buffet, David Kremer, Patrick Küry, David Leppert, Thomas Rückle, Frederik Barkhof
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 28 Issue 3 Pg. 429-440 (Mar 2022) ISSN: 1477-0970 [Electronic] England
• PMID: 34240656 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Double-Blind Method
• Gene Products, env (therapeutic use)
• Humans
• Magnetic Resonance Imaging
• Multiple Sclerosis (drug therapy)
• Multiple Sclerosis, Relapsing-Remitting (diagnostic imaging, drug therapy, pathology)
• Treatment Outcome