Long-term safety, tolerability, and efficacy of subcutaneous Efgartigimod PH20 in patients with generalized Myasthenia Gravis – Interim results of the ADAPT-SC+ study

Abstract-Text (inkl. Referenzen und Bildunterschriften)

Introduction: In ADAPT-SC, subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) 1000 mg was shown to have noninferior total IgG reduction to efgartigimod IV 10 mg/kg (approved in US, Japan, and EU) resulting in similar clinical improvement in patients with generalized myasthenia gravis (gMG). Patients completing ADAPT-SC, or enrolled in ADAPT+, were eligible to participate in the ongoing open-label extension, ADAPT-SC+.

Objective: To evaluate long-term safety, tolerability, and efficacy of efgartigimod PH20 SC in patients with gMG enrolled in the ADAPT-SC+ open-label extension study.

Methods: Efgartigimod PH20 SC 1000mg was administered in cycles of 4-weekly injections. Subsequent cycles were initiated at least 28 days from the last dose based on clinical evaluation. Clinical efficacy was assessed utilizing the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale.

Results: As of March 2022, 164 participants received ≥1 dose of efgartigimod PH20 SC. Patients received ~3 cycles over a mean (SD) study duration of 170 (59) days, resulting in 72 patient-years of observation. Adverse events (AEs) were predominantly mild/moderate. The most frequent AEs were injection site erythema (25.6%), headache (15.2%), and COVID-19 (11.6%). All injection site reactions (ISRs) were mild/moderate and did not lead to treatment discontinuation. ISRs typically occurred within 24 hours of administration, resolved spontaneously, and incidence decreased with subsequent cycles. Two deaths were reported (metastatic renal cancer and COVID-19); neither were deemed efgartigimod-related per investigator. Improvement from cycle baseline in MG-ADL total score (mean [SE] improvement at week 4: –4.0 [0.25]) was observed in cycle 1, with consistent and repeatable improvements seen in subsequent cycles. Long-term treatment with efgartigimod PH20 SC 1000 mg reduced disease severity, as assessed by the MG-ADL scale, and improved the quality of life of patients with gMG. Speed of onset, magnitude, and repeatability of improvements in MG-ADL were similar to those with efgartigimod IV during ADAPT/ADAPT+.

Conclusion: Results suggest multiple cycles of efgartigimod PH20 SC were well tolerated, with no safety concerns identified compared to ADAPT-SC. Treatment with efgartigimod PH20 SC led to consistent and repeatable reductions in MG-ADL total score, and the observed efficacy profile was consistent with ADAPT/ADAPT+.