Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis: A Phase 2 Randomized Control Trial

Abstract

Objective: To 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).

Methods: In 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 was change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints were change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores and safety.

Results: Forty-three patients were randomized (rozanolixizumab 21, placebo 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo was as follows: QMG (LS mean -1.8 vs -1.2, difference -0.7, 95% upper confidence limit [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%).

Conclusion: Whereas 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 evidence: This study provides Class I evidence that for patients with gMG, rozanolixizumab is well-tolerated, but did not significantly improve QMG score.

Figure 1. CONSORT (Consolidated Standards of Reporting Trials) Diagram

^aDid not meet inclusion criteria. ^bDiscontinued treatment due to a severe adverse event (AE) (headache) but continued in the observation period.

Figure 2. Change in Measures of Clinical Effect from Baseline to Day 29 (Period 1)

Change from baseline to day 29 in (A) Quantitative Myasthenia Gravis (QMG) score, (B) Myasthenia Gravis–Activities of Daily Living (MG-ADL) score, and (C) Myasthenia Gravis–Composite (MGC) score. Data are least squares (LS) mean change from baseline of the full analysis set; error bars show SEM. CI = confidence interval; SEM = standard error of the mean.

Figure 3. Responder Rate Analysis (Full Analysis Set) at Day 29 for Measures of Clinical Effect

Day 29 responder rates (≥3.0-point improvement from baseline) for (A) Quantitative Myasthenia Gravis (QMG) score, (B) Myasthenia Gravis–Activities of Daily Living (MG-ADL) score, and (C) Myasthenia Gravis–Composite (MGC) score.

Figure 4. Change From Baseline in Measures of Clinical Effect (Full Analysis Set) According to Periods 1 and 2

Change from baseline for (A) Quantitative Myasthenia Gravis (QMG) score, (B) Myasthenia Gravis–Activities of Daily Living (MG-ADL) score, and (C) Myasthenia Gravis–Composite (MGC) score. SEM = standard error of the mean.

Figure 5. Mean Percent Change From Baseline in Serum Immunoglobulin G (IgG) (Pharmacodynamic per Protocol Analysis Set) and Anti–acetylcholine Receptor (AChR) (Full Analysis Set [FAS]) Following Rozanolixizumab Treatment

(A) Serum IgG concentration. (B) Serum AChR autoantibody concentration. Data are from FAS group members who were AChR-positive at baseline; up to 40 patients in period 1 and up to 39 patients in period 2 are included in the analysis. For both graphs, data are presented as mean percent change from baseline, error bars show standard error of the mean (SEM).