Rozanolixizumab in generalized myasthenia gravis: Pooled analysis of the Phase 3 MycarinG study and two open-label extensions.

Abstract

Background: Myasthenia gravis (MG) is a chronic autoimmune disease causing fluctuating muscle weakness. The MycarinG study showed that rozanolixizumab, a neonatal Fc receptor inhibitor, provided clinically meaningful improvements in MG outcomes in patients with acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) autoantibody-positive generalized MG (gMG).

Objective: We assessed efficacy and safety of 6-week rozanolixizumab treatment cycles in patients with gMG.

Methods: Following MycarinG, eligible patients enrolled in the open-label extension Phase 3 studies MG0004 (NCT04124965) to receive up to 52 weekly rozanolixizumab infusions or MG0007 (NCT04650854) to receive cycles of 6 weekly rozanolixizumab infusions (initiated on symptom worsening at investigators' discretion). To assess the effect of repeated cyclical treatment, data were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 (interim analysis). Efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Composite (MGC) and Quantitative Myasthenia Gravis (QMG) assessed in patients who received ≥2 symptom-driven treatment cycles. Treatment-emergent adverse events (TEAEs) were assessed in patients who received ≥1 cycle and had an (up to) 8-week follow-up period.

Results: At data cut-off (July 8, 2022), 188/196 (95.9%) patients received ≥1 treatment cycle with a follow-up period (primary safety pool; MycarinG/MG0007) and 127 (64.8%) received ≥2 symptom-driven cycles (primary efficacy pool; MycarinG/MG0004 [first 6 weeks]/MG0007). Consistent and clinically meaningful improvements in MG-ADL, MGC and QMG scores, and high MG-ADL, MGC and QMG response rates, were observed at the end of the first symptom-driven cycle and subsequent cycles. TEAEs were experienced by 169/188 (89.9%) patients and were mostly mild to moderate. TEAEs did not increase with repeated cycles.

Conclusions: Repeated cycles of rozanolixizumab resulted in consistent, clinically meaningful improvements across cycles in MG-specific outcomes with an acceptable safety profile, supporting rozanolixizumab as a treatment option for adults with AChR and MuSK autoantibody-positive gMG.