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+).

Background: 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. Methods: 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. Results: 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. Discussion: 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. Clinical trial registration: https://clinicaltrials.gov/study/NCT04818671, NCT04818671.