Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis
ObjectiveADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).MethodsADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1284444/full |
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| author | James F. Howard Vera Bril Tuan Vu Chafic Karam Stojan Peric Jan L. De Bleecker Hiroyuki Murai Andreas Meisel Said R. Beydoun Mamatha Pasnoor Antonio Guglietta Benjamin Van Hoorick Sophie Steeland Caroline T’joen Kimiaki Utsugisawa Jan Verschuuren Renato Mantegazza the ADAPT+ Study Group |
| author_facet | James F. Howard Vera Bril Tuan Vu Chafic Karam Stojan Peric Jan L. De Bleecker Hiroyuki Murai Andreas Meisel Said R. Beydoun Mamatha Pasnoor Antonio Guglietta Benjamin Van Hoorick Sophie Steeland Caroline T’joen Kimiaki Utsugisawa Jan Verschuuren Renato Mantegazza the ADAPT+ Study Group |
| author_sort | James F. Howard |
| collection | DOAJ |
| description | ObjectiveADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).MethodsADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.ResultsAs of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab−. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab− participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5–7.6]).ConclusionResults of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403. |
| first_indexed | 2024-03-08T12:13:38Z |
| format | Article |
| id | doaj.art-1a89a0788ce640369ff168f37dc4e637 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-08T12:13:38Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-1a89a0788ce640369ff168f37dc4e6372024-01-22T17:30:31ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-01-011410.3389/fneur.2023.12844441284444Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravisJames F. Howard0Vera Bril1Tuan Vu2Chafic Karam3Stojan Peric4Jan L. De Bleecker5Hiroyuki Murai6Andreas Meisel7Said R. Beydoun8Mamatha Pasnoor9Antonio Guglietta10Benjamin Van Hoorick11Sophie Steeland12Caroline T’joen13Kimiaki Utsugisawa14Jan Verschuuren15Renato Mantegazza16the ADAPT+ Study GroupDepartment of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesEllen and Martin Prosserman Centre for Neuromuscular Diseases, University Health Network, University of Toronto, Toronto, ON, CanadaDepartment of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, United StatesPenn Neuroscience Center-Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, United StatesNeurology Clinic, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of Neurology and Neuromuscular Reference Center, Ghent University Hospital, Ghent, BelgiumDepartment of Neurology, School of Medicine, International University of Health and Welfare, Narita, JapanDepartment of Neurology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States0Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States1argenx, Ghent, Belgium1argenx, Ghent, Belgium1argenx, Ghent, Belgium1argenx, Ghent, Belgium2Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan3Department of Neurology, Leiden University Medical Center, Leiden, Netherlands4Department of Neuroimmunology and Neuromuscular Diseases, Fondazione Istituto Carlo Besta, Milan, ItalyObjectiveADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).MethodsADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.ResultsAs of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab−. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab− participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5–7.6]).ConclusionResults of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403.https://www.frontiersin.org/articles/10.3389/fneur.2023.1284444/fullefgartigimodmyasthenia gravisneonatal Fc receptorFcRnIgG recyclingantibody fragment |
| spellingShingle | James F. Howard Vera Bril Tuan Vu Chafic Karam Stojan Peric Jan L. De Bleecker Hiroyuki Murai Andreas Meisel Said R. Beydoun Mamatha Pasnoor Antonio Guglietta Benjamin Van Hoorick Sophie Steeland Caroline T’joen Kimiaki Utsugisawa Jan Verschuuren Renato Mantegazza the ADAPT+ Study Group Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis Frontiers in Neurology efgartigimod myasthenia gravis neonatal Fc receptor FcRn IgG recycling antibody fragment |
| title | Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis |
| title_full | Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis |
| title_fullStr | Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis |
| title_full_unstemmed | Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis |
| title_short | Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis |
| title_sort | long term safety tolerability and efficacy of efgartigimod adapt interim results from a phase 3 open label extension study in participants with generalized myasthenia gravis |
| topic | efgartigimod myasthenia gravis neonatal Fc receptor FcRn IgG recycling antibody fragment |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1284444/full |
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