Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study-Reference-Cited by-同舟云学术

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

Published:2021-07-09 Issue: Volume: Page:135245852110249
ISSN:1352-4585
Container-title:Multiple Sclerosis Journal
language:en
Short-container-title:Mult Scler

Author:

Hartung Hans-Peter¹,Derfuss Tobias²^ORCID,Cree Bruce AC³^ORCID,Sormani Maria Pia⁴^ORCID,Selmaj Krzysztof⁵,Stutters Jonathan⁶,Prados Ferran⁷,MacManus David⁶^ORCID,Schneble Hans-Martin⁸,Lambert Estelle⁹,Porchet Hervé¹⁰,Glanzman Robert¹¹,Warne David¹¹,Curtin Francois¹²,Kornmann Gabrielle¹¹,Buffet Bénédicte¹¹,Kremer David¹³,Küry Patrick¹³,Leppert David¹⁴,Rückle Thomas¹¹,Barkhof Frederik¹⁵

Affiliation:

1. Department of Neurology, Universitätsklinikum Düsseldorf (UKD) and Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany/Center for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany/Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia/Department of Neurology, Medical University of Vienna, Vienna, Austria

2. Department of Neurology, Universitätsspital Basel, Basel, Switzerland

3. Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA

4. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy/Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Policlinico San Martino, Genova, Italy

5. Department of Neurology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland/Department of Neurology, Medical Academy of Łódź, Łódź, Poland

6. Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK

7. Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK; Universitat Oberta de Catalunya, Barcelona, Spain

8. Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK

9. Institut de Recherches Internationales Servier, Suresnes, France

10. GeNeuro SA, Geneva, Switzerland/Department of Pharmacology, University of Pretoria, Pretoria, South Africa

11. GeNeuro SA, Geneva, Switzerland

12. GeNeuro SA, Geneva, Switzerland; Clinical Pharmacology and Toxicology Division, Geneva University Hospitals, Geneva, Switzerland

13. Department of Neurology, Universitätsklinikum Düsseldorf (UKD) and Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany/Center for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

14. Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia/GeNeuro SA, Geneva, Switzerland

15. Nuclear Magnetic Resonance (NMR) Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK/Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK/Department of Radiology and Nuclear Medicine, VU University Medical Center Amsterdam, Amsterdam, The Netherlands

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

Funder

GeNeuro

servier

Publisher

SAGE Publications

Subject

Clinical Neurology,Neurology

Link

http://journals.sagepub.com/doi/pdf/10.1177/13524585211024997

Reference18 articles.

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