Efficacy and safety of rozanolixizumab in moderate-to-severe generalised myasthenia gravis

ObjectiveTo explore the clinical efficacy and safety of subcutaneous (SC) rozanolixizumab, an anti-neonatal Fc receptor humanized monoclonal antibody, in patients with generalized myasthenia gravis (gMG).MethodsIn this phase 2a, randomized, double-blind, placebo-controlled, 2-period, multicenter trial (NCT03052751), patients were randomized (1:1) in period 1 (days 1–29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg or placebo. In period 2 (days 29–43), patients were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions), followed by an observation period (days 44–99). Primary endpoint: change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints: change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores; safety.ResultsForty-three patients were randomized (rozanolixizumab: 21 patients; placebo: 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo: QMG (LS mean: −1.8 vs −1.2; difference: −0.7; 95% UCL: 0.8; p = 0.221; not statistically significant), MG-ADL (LS mean: −1.8 vs −0.4; difference: −1.4; 95% UCL: −0.4), and MGC (LS mean: −3.1 vs −1.2; difference: −1.8; 95% UCL: 0.4) scores. Efficacy measures continued to improve with rozanolixizumab 7 mg/kg in period 2. The most common adverse event in period 1 was headache (rozanolixizumab: 57%; placebo: 14%).ConclusionWhile change from baseline in QMG was not statistically significant, the data overall suggest rozanolixizumab may provide clinical benefit in patients with gMG and was generally well tolerated. Phase 3 evaluation is ongoing (NCT03971422).Classification of evidenceThis study provides class I evidence that for patients with gMG, rozanolixizumab is well tolerated, but did not significantly improve QMG score.