Long-term safety, tolerability, and efficacy of subcutaneous efgartigimod PH20 in generalized myasthenia gravis: final results from a phase 3 open-label extension study (ADAPT-SC+).

Efgartigimod is a human immunoglobulin (IgG1) antibody Fc fragment that reduces IgG levels through neonatal Fc receptor blockade. ADAPT-SC+ assessed the long-term safety, tolerability, and efficacy of subcutaneous (SC) efgartigimod PH20 in adult participants with generalized myasthenia gravis (gMG). Previously, ADAPT-SC demonstrated noninferiority of efgartigimod PH20 SC to intravenous efgartigimod. ADAPT-SC+ was a single-arm, multicenter, open-label extension study. Efgartigimod PH20 SC 1000 mg was administered in treatment cycles of 4 once-weekly injections, with timing of cycles individualized based on clinical evaluation. During the first year of the study, ≥4 weeks were required between cycles; in the second year and onward, participants consenting to a protocol amendment could have ≥1 week between cycles. A total of 184 participants rolled over from ADAPT+ and ADAPT-SC, and 180 participants received ≥1 dose of efgartigimod PH20 SC. The mean (SD) treatment plus follow-up time was 2.6 (0.9) years, corresponding to 459.4 total participant years of follow-up, with a maximum of 33 treatment cycles. Overall, 169 (93.9%) participants experienced ≥1 treatment-emergent adverse event (TEAE), and the most frequent TEAEs were injection site reactions (ISRs; n = 83, 46.1%), COVID-19 (n = 53, 29.4%), and headache (n = 48, 26.7%). ISRs were mild or moderate in severity. No new safety signals were observed in participants with more frequent dosing (<4 weeks between cycles) after the protocol amendment. Rapid and clinically meaningful improvements (CMI, reduction of ≥2 points) in mean Myasthenia Gravis Activities of Daily Living (MG-ADL) total scores were observed. During the study, 95.1% of participants with acetylcholine receptor antibody-positive (AChR-Ab+) gMG and 94.7% of participants with AChR-Ab- gMG achieved CMI at any point. Many participants demonstrated substantial clinical improvements, with 59.2% of participants with AChR-Ab+ gMG and 34.2% of participants with AChR-Ab- gMG achieving minimal symptom expression (MSE; MG-ADL, 0-1). The majority of participants who achieved MSE (83.3% with AChR-Ab+ gMG, 53.8% with AChR-Ab- gMG) experienced sustained MSE at consecutive assessments covering ≥8 weeks. The results of ADAPT-SC+ demonstrate long-term safety, tolerability, and sustained efficacy of efgartigimod PH20 SC across various dosing approaches, building on previous studies to broaden options for individualizing treatment for patients with gMG. https://clinicaltrials.gov/study/NCT04818671, NCT04818671.