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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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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. |
format | Online Article Text |
id | pubmed-7604551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
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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