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Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing–remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be simi...

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Autores principales: Naismith, Robert T, Wolinsky, Jerry S, Wundes, Annette, LaGanke, Christopher, Arnold, Douglas L, Obradovic, Dragana, Freedman, Mark S, Gudesblatt, Mark, Ziemssen, Tjalf, Kandinov, Boris, Bidollari, Ilda, Lopez-Bresnahan, Maria, Nangia, Narinder, Rezendes, David, Yang, Lili, Chen, Hailu, Liu, Shifang, Hanna, Jerome, Miller, Catherine, Leigh-Pemberton, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604551/
https://www.ncbi.nlm.nih.gov/pubmed/31680631
http://dx.doi.org/10.1177/1352458519881761
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author Naismith, Robert T
Wolinsky, Jerry S
Wundes, Annette
LaGanke, Christopher
Arnold, Douglas L
Obradovic, Dragana
Freedman, Mark S
Gudesblatt, Mark
Ziemssen, Tjalf
Kandinov, Boris
Bidollari, Ilda
Lopez-Bresnahan, Maria
Nangia, Narinder
Rezendes, David
Yang, Lili
Chen, Hailu
Liu, Shifang
Hanna, Jerome
Miller, Catherine
Leigh-Pemberton, Richard
author_facet Naismith, Robert T
Wolinsky, Jerry S
Wundes, Annette
LaGanke, Christopher
Arnold, Douglas L
Obradovic, Dragana
Freedman, Mark S
Gudesblatt, Mark
Ziemssen, Tjalf
Kandinov, Boris
Bidollari, Ilda
Lopez-Bresnahan, Maria
Nangia, Narinder
Rezendes, David
Yang, Lili
Chen, Hailu
Liu, Shifang
Hanna, Jerome
Miller, Catherine
Leigh-Pemberton, Richard
author_sort Naismith, Robert T
collection PubMed
description BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing–remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be similar. However, DRF’s distinct chemical structure may result in a differentiated gastrointestinal (GI) tolerability profile. OBJECTIVE: To report interim safety/efficacy findings from patients in the ongoing EVOLVE-MS-1 study. METHODS: EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in RRMS patients. Primary endpoint is safety and tolerability; efficacy endpoints are exploratory. RESULTS: As of March 2018, 696 patients were enrolled; median exposure was 59.9 (range: 0.1–98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At Week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77%; p < 0.0001) and adjusted annualized relapse rate was low (0.16; 95% confidence interval: 0.13–0.20). CONCLUSION: Interim data from EVOLVE-MS-1 suggest DRF is a well-tolerated treatment with a favorable safety/efficacy profile for patients with RRMS.
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spelling pubmed-76045512020-11-17 Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study Naismith, Robert T Wolinsky, Jerry S Wundes, Annette LaGanke, Christopher Arnold, Douglas L Obradovic, Dragana Freedman, Mark S Gudesblatt, Mark Ziemssen, Tjalf Kandinov, Boris Bidollari, Ilda Lopez-Bresnahan, Maria Nangia, Narinder Rezendes, David Yang, Lili Chen, Hailu Liu, Shifang Hanna, Jerome Miller, Catherine Leigh-Pemberton, Richard Mult Scler Original Research Papers BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing–remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be similar. However, DRF’s distinct chemical structure may result in a differentiated gastrointestinal (GI) tolerability profile. OBJECTIVE: To report interim safety/efficacy findings from patients in the ongoing EVOLVE-MS-1 study. METHODS: EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in RRMS patients. Primary endpoint is safety and tolerability; efficacy endpoints are exploratory. RESULTS: As of March 2018, 696 patients were enrolled; median exposure was 59.9 (range: 0.1–98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At Week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77%; p < 0.0001) and adjusted annualized relapse rate was low (0.16; 95% confidence interval: 0.13–0.20). CONCLUSION: Interim data from EVOLVE-MS-1 suggest DRF is a well-tolerated treatment with a favorable safety/efficacy profile for patients with RRMS. SAGE Publications 2019-11-04 2020-11 /pmc/articles/PMC7604551/ /pubmed/31680631 http://dx.doi.org/10.1177/1352458519881761 Text en © The Author(s), 2019 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Papers
Naismith, Robert T
Wolinsky, Jerry S
Wundes, Annette
LaGanke, Christopher
Arnold, Douglas L
Obradovic, Dragana
Freedman, Mark S
Gudesblatt, Mark
Ziemssen, Tjalf
Kandinov, Boris
Bidollari, Ilda
Lopez-Bresnahan, Maria
Nangia, Narinder
Rezendes, David
Yang, Lili
Chen, Hailu
Liu, Shifang
Hanna, Jerome
Miller, Catherine
Leigh-Pemberton, Richard
Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study
title Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study
title_full Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study
title_fullStr Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study
title_full_unstemmed Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study
title_short Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study
title_sort diroximel fumarate (drf) in patients with relapsing–remitting multiple sclerosis: interim safety and efficacy results from the phase 3 evolve-ms-1 study
topic Original Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604551/
https://www.ncbi.nlm.nih.gov/pubmed/31680631
http://dx.doi.org/10.1177/1352458519881761
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