Following the positive phase 3 findings, UCB plans to file regulatory submissions for both zilucoplan and rozanolixizumab later this year.
At the 14th Myasthenia Gravis Foundation of America International Conference on Myasthenia Gravis and Related Disorder, May 10-12, UCB Pharma presented 2 posters on phase 3 studies that evaluated efficacy and safety of their investigational agents zilucoplan and rozanolixizumab for the treatment of adults with generalized myasthenia gravis (gMG).1
All told, both treatments showed significant improvements on key gMG-specific outcomes, mainly the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, relative to placebo. Zilucoplan, a self-administered subcutaneous C5 inhibitor, and rozanolixizumab, a subcutaneously infused monoclonal antibody targeting the neonatal Fc receptor (FcRn), are both still in clinical development, with regulatory submissions expected to come later this year.
In the RAISE trial (NCT04115293), 174 patients with acetylcholine receptor antibody positive (AChR+) gMG were randomized to zilucoplan 0.3 mg/kg (n = 86) daily or placebo (n = 88) over the course of 12 weeks. Originally reported in February 2022, zilucoplan met its primary end point, resulting in a placebo-corrected mean improvement of 2.12 points on MG-ADL score at week 12 (P <.001).
"The results from the RAISE study are an exciting development in the gMG treatment paradigm and reinforce the critical role that complement inhibition could play for physicians treating patients with this debilitating illness,” lead trial investigator James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, chief, Neuromuscular Disorders Section, University of North Carolina School of Medicine, said in a statement.1 “By targeting the underlying mechanisms of gMG at the neuromuscular junction, complement inhibitors like zilucoplan have the potential to provide rapid, consistent disease control earlier in the disease course. These findings are an encouraging sign that we may be able to meet patients’ needs effectively, with treatments that are minimally invasive and well tolerated."
Several secondary end points, including Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Composite, and Myasthenia Gravis Quality of Life 15-Item revised, all showed statistically significant improvements as early as week 1 following zilucoplan treatment initiation. Notably, the proportion of patients on zilucoplan who responded to treatment by at least a 3-point reduction on MG-ADL and at least a 5-point reduction in QMG were also significantly higher than placebo.
Zilucoplan continued to show a safety profile that was consistent with previous studies, with adverse event (AE) rates that were also similar (76.7%) with those on placebo (70.5%). The most common treatment-emergent AEs were injection site bruising, headache, diarrhea, and MG worsening.
Rozanolixizumab, on the other hand, was assessed in a 66-patient phase 3, double-blind, placebo-controlled, study called MycarinG (NCT03971422) Those included were randomized to rozanolixizumab at doses of 7 mg/kg and 10 mg/kg or placebo, and at day 43, treatment with study drug resulted in significant reductions of MG-ADL compared with placebo in patients with AChR or muscle-specific tyrosine kinase autoantibody positive gMG. In the rozanolixizumab 7- and 10-mg/kg dose groups, investigators observed a placebo-corrected mean improvement of 2.586 and 2.619 points in the MG-ADL relative to placebo (both, P <.001).
"The one constant in gMG is unpredictability. People living with this disease experience symptoms that are nebulous, fluctuating, and which vary from one day to the next. For this reason, there is an urgent need for more effective, targeted, and convenient treatments that reduce the burden of disease on patients’ daily lives," lead investigator Vera Bril, MD, FRCPC professor of neurology, University of Toronto, director of the Neuromuscular Section, Division of Neurology, University of Toronto and University Health Network, said in a statement.1 "The results from the MycarinG study are extremely encouraging, and demonstrate the potential of rozanolixizumab as a new, effective and flexible treatment option to help ease the day-to-day burden of this challenging disease and improve treatment outcomes for patients."
Rozanolixizumab was generally well-tolerated and showed an impact on mean maximum immunoglobulin (IgG) levels. In total, the 7- and 10-mg/kg day groups saw reductions of 71% and 78%, respectively, over the treatment period. Most of the treatment-emergent adverse events (TEAEs) were mild to moderate in intensity, with headache as the most reported complication. Notably, a higher proportion of TEAEs occurred in the active treatment groups (rozanolixizumab 7 mg/kg: 81.3%; 10 mg/kg: 82.6%) than placebo (67.2%).
The MG Symptoms PRO, a patient-reported outcome measure developed by UCB with patients used to assess a series of quality-of-life measures, were significantly improved following treatment with rozanolixizumab. Specifically, the 3 scales observed—muscle weakness fatigability, physical fatigue, and bulbar muscle weakness—all had significant improvements at day 43 relative to placebo, indicating that rozanolixizumab improves patient’s symptoms and their ability to undertake daily activities.