Rozanolixizumab was associated with reductions in anti-acetylcholine receptor autoantibodies and was well tolerated across 2 dose levels with no new safety findings.
Results from a phase 2a multicenter trial (NCT03052751) of patients with generalized myasthenia gravis (gMG) demonstrated that treatment with subcutaneous (SC) rozanolixizumab was well tolerated and may provide clinical benefit, despite non-statistically significant changes in Quantitative Myasthenia Gravias (QMG) score.1
Vera Bril, BSc, FRCPC, MD, professor of neurology, director of the Neuromuscular Section, University of Toronto, and colleagues found that least square (LS) mean change from baseline to day 29 on QMG score for those who received rozanolixizumab was –1.8 compared to –1.2 for those on placebo (difference, –0.7; 95% upper confidence level [UCL], 0.8; P = 0.221). Despite improvements, these were statistically insignificant.
Improved day-to-day function, as measured by change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) was observed following treatment with rozanolixizumab compared with placebo (LS mean, –1.8 vs –0.4; difference, –1.4; 95% UCL, –0.4). MG-Composite (MGC) scores for those who were administered the agent also showed changes from baseline to day 29 compared with placebo (LS mean, –3.1 vs –1.2; difference, –1.8; 95% UCL, 0.4).
“This is the first trial to assess the therapeutic potential of rozanolixizumab in patients with gMG and our results across efficacy measures, together with data reported by Howard et al, offer important insights into the validity of inhibition of FcRn as a therapeutic approach in gMC,” Bril et al concluded. Howard et al. assessed the FcRn antagonist efgartigimod in gMG, and observed a correlation between lowering og pathogenic IgG autoantibodies and disease improvement that implied a reduction in pathogenic autoantibodies could be an innovative approach to treat the condition.2
In the randomized, double-blind, placebo-controlled, 2-period study, patients were randomized 1:1 in period 1 (days 1–29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg (n = 21) or placebo (n = 22). Patients then were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions) in period 2 (days 29–43), followed by an observation period (days 44–99).
Bril and colleagues found that day 29 responder rates (≥3.0-point improvement from baseline) were higher in patients receiving rozanolixizumab 7 mg/kg vs placebo for QMG (38% vs 23%, respectively), MG-ADL (48% vs 14%), and MGC (48% vs 27%) scores.
Those who continued treatment of rozanolixizumab in period 2 saw improvements across all 3 scoring measures. QMG and MG-ADL scores reached a maximum reduction 21 days after re-initiation of rozanolixizumab 7 mg/kg treatment.
Patients re-randomized from rozanolixizumab 7 mg/kg to rozanolixizumab 4 mg/kg in period 2 maintained modest reductions for QMG, MG-ADL, and MGC scores from day 29. Nadir was observed for all 3 measures 21 days after the first rozanolixizumab 4 mg/kg dose was administered. Notably, QMG score reductions were maintained to day 78.
During dosing period 1, 16 of 21 (76%) patients receiving rozanolixizumab and 16 of 22 (73%) patients receiving placebo reported at least 1 adverse event (AE). Zero serious AEs occurred in the rozanolixizumab group while 2 (9%) patients receiving placebo reported serious AEs. Headache, which occurred in 57% of patients in the rozanolixizumab group and 14% of patients on placebo, was among the most common AE in period 1.
The presence of immunoglobulin G (IgG) autoantibodies that impair synaptic transmission at the neuromuscular junction, have been documented as a driving force in patients with MG. Exploratory analyses showed a reduction in total serum IgG concentration for all dose groups after administration of rozanolixizumab.
Treatment with rozanolixizumab in period 1 resulted in a rapid reduction of IgG concentrations vs placebo (52% vs 4%, respectively). Additionally, the lowest point in IgG concentration following rozanolixizumab treatment occurred by day 22 (61%). Continuation of rozanolixizumab 7 mg/kg following period 2 re-randomization further reduced IgG concentration (maximum decrease 68% by day 50).
Rozanolixizumab, an SC-infused neonatal Fc receptor (FcRn), is also being evaluated in an ongoing phase 3 study (NCT03971422). The randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of rozanolixizumab in an estimated 240 patients with gMG and is expected to conclude sometime around May 2021.