Abstract Details

gMG, a rare autoimmune disease affecting the neuromuscular junction, results in fatigable skeletal muscle weakness. Pre-clinical and clinical data implicate IL-6 in the pathology of MG, suggesting its therapeutic target viability. Satralizumab, a humanized IL-6 receptor monoclonal recycling antibody, provides durable inhibition of IL-6 signaling, which has the potential to modulate upstream immunopathogenic mechanisms in gMG. Satralizumab is approved for the treatment of anti-aquaporin-4-seropositive neuromyelitis optica spectrum disorder, with long-term (~9 years) experience regarding its benefit:risk profile. This is the first report of data assessing IL-6 signaling inhibition with satralizumab in gMG, and will inform on the benefit:risk profile of satralizumab in gMG.

To report primary and notable secondary efficacy and safety results of LUMINESCE (NCT04963270), a Phase 3 study investigating satralizumab in patients aged ≥12 years with generalized myasthenia gravis (gMG).

Eligibility criteria included gMG seropositivity (AChR-IgG+, MuSK-IgG+, or LRP4-IgG+), an MGFA severity class II–IV, an MG-ADL score ≥5 (non-ocular contribution >50%), and use of stable background therapy. Participants were randomized 1:1 to receive subcutaneous satralizumab or placebo at Weeks 0, 2, 4, and Q4W thereafter until Week 24. The primary efficacy endpoint was mean change from baseline in total MG-ADL score at Week 24 (AChR-IgG+). Secondary efficacy endpoints include, but are not limited to, mean change from baseline in QMG score, percentage of patients with ≥2 points reduction in total MG-ADL score, and percentage of patients with ≥3 points reduction in QMG score, at Week 24 (AChR-IgG+); and durability of efficacy of satralizumab. Safety analyses included incidence and severity of adverse events.

To date, 186 participants were randomized. Baseline demographics, and primary and notable secondary efficacy and safety results will be presented.

LUMINESCE, the first study of IL-6 signaling inhibition with satralizumab in gMG, will generate important data to evaluate satralizumab’s efficacy and safety in gMG.