Open AccessEfficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study
Author(s) -
Hans Peter Hartung,
Tobias Derfuss,
Bruce A.C. Cree,
Maria Pia Sormani,
Krzysztof Selmaj,
Jon Stutters,
Ferrán Prados,
David MacManus,
Hans Martin Schneble,
Estelle V. Lambert,
Hervé Porchet,
Robert Glanzman,
David W. Warne,
François Curtin,
Gabrielle Kornmann,
Bénédicte Buffet,
David Kremer,
Patrick Küry,
David Leppert,
Thomas Rückle,
Frederik Barkhof
Publication year - 2021
Publication title -
multiple sclerosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.729
H-Index - 131
eISSN - 1477-0970
pISSN - 1352-4585
DOI - 10.1177/13524585211024997
Subject(s) - clinical endpoint , medicine , multiple sclerosis , placebo , atrophy , magnetic resonance imaging , randomized controlled trial , adverse effect , magnetization transfer , phases of clinical research , clinical trial , pathology , radiology , immunology , alternative medicine
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