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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| Veröffentlicht in: | Multiple sclerosis 2020-11, Vol.26 (13), p.1729-1739 |
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| creator | 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 |
| 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 |
| doi_str_mv | 10.1177/1352458519881761 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7604551</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458519881761</sage_id><sourcerecordid>2311925200</sourcerecordid><originalsourceid>FETCH-LOGICAL-c462t-eaece2c21cfcb6ddfd0f44f770869043f7b643ece4193474430c998d38162c723</originalsourceid><addsrcrecordid>eNp1kTtvFDEUhS0EIiHQUyFLNKEY8GvsGQoklGwg0qJIPNJaXs_1riPPI7YH2I7_QMfP45fgaEOASFS-0v3OsY8PQo8peU6pUi8or5mom5q2TUOVpHfQPhVKVaRV5G6Zy7q62u-hByldEEKU4vV9tMepbIjkdB_9OPZx_Op7CNjNvYkmAz48fn_yDPsBTyZ7GHLCX3ze4AjBTMkP65_fvkfofc5lxv0csp8C4GQDxDH59BKfDhmi73EyDvIWm6HD4Jy3xm6LSyqKhF0ce5w3gKeNSYA5XpyfLc8X1bsPFcUpz932IbrnTEjw6Po8QJ9OFh-P3lbLszenR6-XlRWS5QoMWGCWUevsSnad64gTwilFGtkSwZ1aScELI2jLhRKCE9u2TccbKplVjB-gVzvfaV710NmSOJqgp5LAxK0ejdf_bga_0evxs1aSiLqmxeDw2iCOlzOkrHufLIRgBhjnpBmntGU1I6SgT2-hF-MchxJPlyIFl03NZKHIjrLlQ1MEd_MYSvRV8fp28UXy5O8QN4LfTReg2gHJrOHPrf81_AXL6LhH</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2454368526</pqid></control><display><type>article</type><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><source>SAGE Complete A-Z List</source><creator>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</creator><creatorcontrib>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</creatorcontrib><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.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458519881761</identifier><identifier>PMID: 31680631</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Gadolinium ; Metabolites ; Multiple sclerosis ; Original Research Papers ; Safety</subject><ispartof>Multiple sclerosis, 2020-11, Vol.26 (13), p.1729-1739</ispartof><rights>The Author(s), 2019</rights><rights>The Author(s), 2019 2019 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-eaece2c21cfcb6ddfd0f44f770869043f7b643ece4193474430c998d38162c723</citedby><cites>FETCH-LOGICAL-c462t-eaece2c21cfcb6ddfd0f44f770869043f7b643ece4193474430c998d38162c723</cites><orcidid>0000-0001-8799-8202 ; 0000-0002-8197-2762</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458519881761$$EPDF$$P50$$Gsage$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458519881761$$EHTML$$P50$$Gsage$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31680631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naismith, Robert T</creatorcontrib><creatorcontrib>Wolinsky, Jerry S</creatorcontrib><creatorcontrib>Wundes, Annette</creatorcontrib><creatorcontrib>LaGanke, Christopher</creatorcontrib><creatorcontrib>Arnold, Douglas L</creatorcontrib><creatorcontrib>Obradovic, Dragana</creatorcontrib><creatorcontrib>Freedman, Mark S</creatorcontrib><creatorcontrib>Gudesblatt, Mark</creatorcontrib><creatorcontrib>Ziemssen, Tjalf</creatorcontrib><creatorcontrib>Kandinov, Boris</creatorcontrib><creatorcontrib>Bidollari, Ilda</creatorcontrib><creatorcontrib>Lopez-Bresnahan, Maria</creatorcontrib><creatorcontrib>Nangia, Narinder</creatorcontrib><creatorcontrib>Rezendes, David</creatorcontrib><creatorcontrib>Yang, Lili</creatorcontrib><creatorcontrib>Chen, Hailu</creatorcontrib><creatorcontrib>Liu, Shifang</creatorcontrib><creatorcontrib>Hanna, Jerome</creatorcontrib><creatorcontrib>Miller, Catherine</creatorcontrib><creatorcontrib>Leigh-Pemberton, Richard</creatorcontrib><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><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><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.</description><subject>Gadolinium</subject><subject>Metabolites</subject><subject>Multiple sclerosis</subject><subject>Original Research Papers</subject><subject>Safety</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><recordid>eNp1kTtvFDEUhS0EIiHQUyFLNKEY8GvsGQoklGwg0qJIPNJaXs_1riPPI7YH2I7_QMfP45fgaEOASFS-0v3OsY8PQo8peU6pUi8or5mom5q2TUOVpHfQPhVKVaRV5G6Zy7q62u-hByldEEKU4vV9tMepbIjkdB_9OPZx_Op7CNjNvYkmAz48fn_yDPsBTyZ7GHLCX3ze4AjBTMkP65_fvkfofc5lxv0csp8C4GQDxDH59BKfDhmi73EyDvIWm6HD4Jy3xm6LSyqKhF0ce5w3gKeNSYA5XpyfLc8X1bsPFcUpz932IbrnTEjw6Po8QJ9OFh-P3lbLszenR6-XlRWS5QoMWGCWUevsSnad64gTwilFGtkSwZ1aScELI2jLhRKCE9u2TccbKplVjB-gVzvfaV710NmSOJqgp5LAxK0ejdf_bga_0evxs1aSiLqmxeDw2iCOlzOkrHufLIRgBhjnpBmntGU1I6SgT2-hF-MchxJPlyIFl03NZKHIjrLlQ1MEd_MYSvRV8fp28UXy5O8QN4LfTReg2gHJrOHPrf81_AXL6LhH</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Naismith, Robert T</creator><creator>Wolinsky, Jerry S</creator><creator>Wundes, Annette</creator><creator>LaGanke, Christopher</creator><creator>Arnold, Douglas L</creator><creator>Obradovic, Dragana</creator><creator>Freedman, Mark S</creator><creator>Gudesblatt, Mark</creator><creator>Ziemssen, Tjalf</creator><creator>Kandinov, Boris</creator><creator>Bidollari, Ilda</creator><creator>Lopez-Bresnahan, Maria</creator><creator>Nangia, Narinder</creator><creator>Rezendes, David</creator><creator>Yang, Lili</creator><creator>Chen, Hailu</creator><creator>Liu, Shifang</creator><creator>Hanna, Jerome</creator><creator>Miller, Catherine</creator><creator>Leigh-Pemberton, Richard</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8799-8202</orcidid><orcidid>https://orcid.org/0000-0002-8197-2762</orcidid></search><sort><creationdate>20201101</creationdate><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><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-eaece2c21cfcb6ddfd0f44f770869043f7b643ece4193474430c998d38162c723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Gadolinium</topic><topic>Metabolites</topic><topic>Multiple sclerosis</topic><topic>Original Research Papers</topic><topic>Safety</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naismith, Robert T</creatorcontrib><creatorcontrib>Wolinsky, Jerry S</creatorcontrib><creatorcontrib>Wundes, Annette</creatorcontrib><creatorcontrib>LaGanke, Christopher</creatorcontrib><creatorcontrib>Arnold, Douglas L</creatorcontrib><creatorcontrib>Obradovic, Dragana</creatorcontrib><creatorcontrib>Freedman, Mark S</creatorcontrib><creatorcontrib>Gudesblatt, Mark</creatorcontrib><creatorcontrib>Ziemssen, Tjalf</creatorcontrib><creatorcontrib>Kandinov, Boris</creatorcontrib><creatorcontrib>Bidollari, Ilda</creatorcontrib><creatorcontrib>Lopez-Bresnahan, Maria</creatorcontrib><creatorcontrib>Nangia, Narinder</creatorcontrib><creatorcontrib>Rezendes, David</creatorcontrib><creatorcontrib>Yang, Lili</creatorcontrib><creatorcontrib>Chen, Hailu</creatorcontrib><creatorcontrib>Liu, Shifang</creatorcontrib><creatorcontrib>Hanna, Jerome</creatorcontrib><creatorcontrib>Miller, Catherine</creatorcontrib><creatorcontrib>Leigh-Pemberton, Richard</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naismith, Robert T</au><au>Wolinsky, Jerry S</au><au>Wundes, Annette</au><au>LaGanke, Christopher</au><au>Arnold, Douglas L</au><au>Obradovic, Dragana</au><au>Freedman, Mark S</au><au>Gudesblatt, Mark</au><au>Ziemssen, Tjalf</au><au>Kandinov, Boris</au><au>Bidollari, Ilda</au><au>Lopez-Bresnahan, Maria</au><au>Nangia, Narinder</au><au>Rezendes, David</au><au>Yang, Lili</au><au>Chen, Hailu</au><au>Liu, Shifang</au><au>Hanna, Jerome</au><au>Miller, Catherine</au><au>Leigh-Pemberton, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>26</volume><issue>13</issue><spage>1729</spage><epage>1739</epage><pages>1729-1739</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><abstract>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.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>31680631</pmid><doi>10.1177/1352458519881761</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8799-8202</orcidid><orcidid>https://orcid.org/0000-0002-8197-2762</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1352-4585 |
| ispartof | Multiple sclerosis, 2020-11, Vol.26 (13), p.1729-1739 |
| issn | 1352-4585 1477-0970 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7604551 |
| source | SAGE Complete A-Z List |
| subjects | Gadolinium Metabolites Multiple sclerosis Original Research Papers Safety |
| title | Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study |
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