Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program
•There were no new safety concerns with longer exposure to ozanimod.•Hepatic enzyme elevations were typically asymptomatic and transient.•Macular edema was rare (≤0.4%) and associated with predisposing comorbidities.•7% had ALC
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| Veröffentlicht in: | Multiple sclerosis and related disorders 2021-06, Vol.51, p.102844-102844, Article 102844 |
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| creator | Selmaj, Krzysztof W. Cohen, Jeffrey A Comi, Giancarlo Bar-Or, Amit Arnold, Douglas L Steinman, Lawrence Hartung, Hans Peter Montalban, Xavier Havrdova, Eva Kubala Cree, Bruce A.C. Minton, Neil Sheffield, James K Ding, Ning Kappos, Ludwig |
| description | •There were no new safety concerns with longer exposure to ozanimod.•Hepatic enzyme elevations were typically asymptomatic and transient.•Macular edema was rare (≤0.4%) and associated with predisposing comorbidities.•7% had ALC |
| doi_str_mv | 10.1016/j.msard.2021.102844 |
| format | Article |
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[Display omitted]
Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data.
We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data.
At the data cutoff, 2631 RMS participants had exposure to ozanimod 0.92 mg (mean 32.0 months) and 2787 had exposure to either ozanimod 0.46 or 0.92 mg (mean 37.1 months). The IRs per 1000 person-years (PY) for any TEAE (772.2) and serious TEAEs (33.2) in the overall population were similar to those in the phase 3 population (896.1 and 31.2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE.
Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.</description><identifier>ISSN: 2211-0348</identifier><identifier>EISSN: 2211-0356</identifier><identifier>DOI: 10.1016/j.msard.2021.102844</identifier><identifier>PMID: 33892317</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adverse events ; Clinical trials ; Multiple sclerosis ; Ozanimod ; Safety</subject><ispartof>Multiple sclerosis and related disorders, 2021-06, Vol.51, p.102844-102844, Article 102844</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier B.V.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-8f27ac3e83706aced492cad95acb2c048518956d9d4a2b72a2601750425a1de53</citedby><cites>FETCH-LOGICAL-c404t-8f27ac3e83706aced492cad95acb2c048518956d9d4a2b72a2601750425a1de53</cites><orcidid>0000-0003-4266-0106</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33892317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Selmaj, Krzysztof W.</creatorcontrib><creatorcontrib>Cohen, Jeffrey A</creatorcontrib><creatorcontrib>Comi, Giancarlo</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Arnold, Douglas L</creatorcontrib><creatorcontrib>Steinman, Lawrence</creatorcontrib><creatorcontrib>Hartung, Hans Peter</creatorcontrib><creatorcontrib>Montalban, Xavier</creatorcontrib><creatorcontrib>Havrdova, Eva Kubala</creatorcontrib><creatorcontrib>Cree, Bruce A.C.</creatorcontrib><creatorcontrib>Minton, Neil</creatorcontrib><creatorcontrib>Sheffield, James K</creatorcontrib><creatorcontrib>Ding, Ning</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><title>Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program</title><title>Multiple sclerosis and related disorders</title><addtitle>Mult Scler Relat Disord</addtitle><description>•There were no new safety concerns with longer exposure to ozanimod.•Hepatic enzyme elevations were typically asymptomatic and transient.•Macular edema was rare (≤0.4%) and associated with predisposing comorbidities.•7% had ALC <0.2 × 109/L, not associated with serious or opportunistic infections.•There was no increase in the incidence rate for malignancies compared with phase 3.
[Display omitted]
Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data.
We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data.
At the data cutoff, 2631 RMS participants had exposure to ozanimod 0.92 mg (mean 32.0 months) and 2787 had exposure to either ozanimod 0.46 or 0.92 mg (mean 37.1 months). The IRs per 1000 person-years (PY) for any TEAE (772.2) and serious TEAEs (33.2) in the overall population were similar to those in the phase 3 population (896.1 and 31.2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE.
Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.</description><subject>Adverse events</subject><subject>Clinical trials</subject><subject>Multiple sclerosis</subject><subject>Ozanimod</subject><subject>Safety</subject><issn>2211-0348</issn><issn>2211-0356</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEURYMoVmp_gSBZumlNMpkvwYUUv6BQF7oOafKmpiSTMZkW6q83tbVLs0kI573LPQhdUTKhhBa3q4mLMugJI4ymH1ZxfoIuGKN0TLK8OD2-eTVAoxhXJJ0ip7yg52iQZVXNMlpeIJh_y9Y4r7FpcQAru2jaJXZr25vOAo7KQvDRxDv85r0FjaNsoN8mNiYm4iZ4h_tPwMqa1ihpsYYNWN85aHvcBb8M0l2is0baCKPDPUQfT4_v05fxbP78On2YjRUnvB9XDSulyqDKSlJIBZrXTEld51ItmCK8ymlV54WuNZdsUTLJCkLLnHCWS6ohz4boZr835X6tIfbCmajAWtmCX0fB0gLGioryhGZ7VKV6MUAjumCcDFtBidgpFivxq1jsFIu94jR1fQhYLxzo48yf0ATc7wFINTcGgojKQJu6mACqF9qbfwN-AJhBjrE</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Selmaj, Krzysztof W.</creator><creator>Cohen, Jeffrey A</creator><creator>Comi, Giancarlo</creator><creator>Bar-Or, Amit</creator><creator>Arnold, Douglas L</creator><creator>Steinman, Lawrence</creator><creator>Hartung, Hans Peter</creator><creator>Montalban, Xavier</creator><creator>Havrdova, Eva Kubala</creator><creator>Cree, Bruce A.C.</creator><creator>Minton, Neil</creator><creator>Sheffield, James K</creator><creator>Ding, Ning</creator><creator>Kappos, Ludwig</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4266-0106</orcidid></search><sort><creationdate>20210601</creationdate><title>Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program</title><author>Selmaj, Krzysztof W. ; Cohen, Jeffrey A ; Comi, Giancarlo ; Bar-Or, Amit ; Arnold, Douglas L ; Steinman, Lawrence ; Hartung, Hans Peter ; Montalban, Xavier ; Havrdova, Eva Kubala ; Cree, Bruce A.C. ; Minton, Neil ; Sheffield, James K ; Ding, Ning ; Kappos, Ludwig</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-8f27ac3e83706aced492cad95acb2c048518956d9d4a2b72a2601750425a1de53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adverse events</topic><topic>Clinical trials</topic><topic>Multiple sclerosis</topic><topic>Ozanimod</topic><topic>Safety</topic><toplevel>online_resources</toplevel><creatorcontrib>Selmaj, Krzysztof W.</creatorcontrib><creatorcontrib>Cohen, Jeffrey A</creatorcontrib><creatorcontrib>Comi, Giancarlo</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Arnold, Douglas L</creatorcontrib><creatorcontrib>Steinman, Lawrence</creatorcontrib><creatorcontrib>Hartung, Hans Peter</creatorcontrib><creatorcontrib>Montalban, Xavier</creatorcontrib><creatorcontrib>Havrdova, Eva Kubala</creatorcontrib><creatorcontrib>Cree, Bruce A.C.</creatorcontrib><creatorcontrib>Minton, Neil</creatorcontrib><creatorcontrib>Sheffield, James K</creatorcontrib><creatorcontrib>Ding, Ning</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Multiple sclerosis and related disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Selmaj, Krzysztof W.</au><au>Cohen, Jeffrey A</au><au>Comi, Giancarlo</au><au>Bar-Or, Amit</au><au>Arnold, Douglas L</au><au>Steinman, Lawrence</au><au>Hartung, Hans Peter</au><au>Montalban, Xavier</au><au>Havrdova, Eva Kubala</au><au>Cree, Bruce A.C.</au><au>Minton, Neil</au><au>Sheffield, James K</au><au>Ding, Ning</au><au>Kappos, Ludwig</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program</atitle><jtitle>Multiple sclerosis and related disorders</jtitle><addtitle>Mult Scler Relat Disord</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>51</volume><spage>102844</spage><epage>102844</epage><pages>102844-102844</pages><artnum>102844</artnum><issn>2211-0348</issn><eissn>2211-0356</eissn><abstract>•There were no new safety concerns with longer exposure to ozanimod.•Hepatic enzyme elevations were typically asymptomatic and transient.•Macular edema was rare (≤0.4%) and associated with predisposing comorbidities.•7% had ALC <0.2 × 109/L, not associated with serious or opportunistic infections.•There was no increase in the incidence rate for malignancies compared with phase 3.
[Display omitted]
Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data.
We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data.
At the data cutoff, 2631 RMS participants had exposure to ozanimod 0.92 mg (mean 32.0 months) and 2787 had exposure to either ozanimod 0.46 or 0.92 mg (mean 37.1 months). The IRs per 1000 person-years (PY) for any TEAE (772.2) and serious TEAEs (33.2) in the overall population were similar to those in the phase 3 population (896.1 and 31.2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE.
Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33892317</pmid><doi>10.1016/j.msard.2021.102844</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-4266-0106</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Multiple sclerosis and related disorders, 2021-06, Vol.51, p.102844-102844, Article 102844 |
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| language | eng |
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| source | Alma/SFX Local Collection |
| subjects | Adverse events Clinical trials Multiple sclerosis Ozanimod Safety |
| title | Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program |
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