Study: Zilucoplan, Rozanolixizumab Improve Generalized Myasthenia Gravis Outcomes


Researchers also noted the importance of patient-reported outcomes due to the fluctuating and unpredictable nature of generalized myasthenia gravis and the subjectivity of symptoms.

New data from the phase 3 RAISE and MycarinG studies have found improved generalized myasthenia gravis (gMG)-specific outcomes among patients treated with zilucoplan and rozanolixizumab.

Zilucoplan is a self-administered, subcutaneous peptide inhibitor of complement component 5, and rozanolixizumab is a subcutaneous-infused monoclonal antibody targeting the neonatal Fc receptor in adults with gMG. The results are being presented as posters at the 14th Myasthenia Gravis Foundation of America International Conference on Myasthenia and Related Disorders.

First, data from the phase 3 RAISE trial demonstrated that treatment with zilucoplan (0.3 mg/kg daily) resulted in clinically meaningful and statistically significant improvements in key gMG-specific outcomes compared with placebo in patients with acetylcholine receptor autoantibody positive (AChR) gMG. The study randomized 174 patients to placebo (N=88) and zilucoplan 0.3 mg/kg (N-86), and patient demographics and baseline disease characteristics were generally balanced between treatment arms.

“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,” said James F. Howard, MD, lead investigator in the RAISE trial, in a press release.

The study met its primary endpoint with zilucoplan showing a placebo-corrected mean improvement of 2.12 points in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 12. Significant improvement in the MG-ADL was observed from week 1, according to the study.

The study also met all key secondary endpoints, including statistically significant improvements in the Quantitative Myasthenia Gravis score, Myasthenia Gravis Composite and Myasthenia Gravis Quality of Life 15-Item revised, again with significant improvements observed from week 1. 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.

Researchers in the RAISE trial observed a favorable safety profile and good tolerability, consistent with prior data. A similar rate of treatment-emergent adverse events (TEAEs) was observed between zilucoplan (76.7%) and placebo (70.5%). The most common TEAEs were injection site bruising, headache, diarrhea, and worsening MG.

“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,” Howard said in the press release. “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.”

The phase 3 results from the MycarinG trial also showed promise. The trial randomized 66 patients to rozanolixizumab 7 mg/kg, 67 patients to 10 mg/kg, and 67 patients to placebo. Baseline characteristics were also generally balanced between treatment groups.

Results demonstrated that rozanolixizumab significantly reduced MG-ADL from baseline to day 43 at the 7 mg/kg and 10 mg/kg doses compared with placebo in patients with AChR or muscle-specific tyrosine kinase autoantibody positive gMG. Treatment with rozanolixizumab demonstrated a placebo-corrected mean improvement of 2.586 points at the 7 mg/kg dose and 2.619 points in the MG-ADL at the 10 mg/kg dose compared with placebo.

“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,” said Vera Bril, MD, FRCPC, lead investigator of the MycarinG study, in the press release.

Furthermore, rozanolixizumab treatment reduced mean maximum total IgG levels by more than 70% and anti-AChR autoantibody levels decreased over the treatment period in line with the total IgG reduction. The drug was generally well tolerated, with the majority of TEAEs occurring in the active treatment arms versus placebo. The most frequently reported TEAE was headache, most of which were mild to moderate, with severe headaches managed with OTC analgesic medications. The other most common TEAEs were diarrhea, pyrexia, and nausea.

Researchers also noted the importance of patient-reported outcomes (PRO) due to the fluctuating and unpredictable nature of gMG and the subjectivity of symptoms. Within the MycarinG study, the MG Symptoms PRO measure was used to assess several quality-of-life measures, including muscle weakness fatigability, physical fatigue, and bulbar muscle weakness, throughout the treatment and observation periods.

All 3 symptom scales or subdomains showed significant improvement from baseline with rozanolixizumab 7 mg/kg and 10 mg/kg doses compared with placebo at day 43, demonstrating that the treatment improved patients’ symptoms and their ability to undertake daily activities, according to the investigators.

“The one constant in gMG is unpredictability,” Bril said in the press release. “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.”


UCB presents efficacy and safety results for zilucoplan and rozanolixizumab in generalized myasthenia gravis. News release. UCB; May 10, 2022. Accessed May 10, 2022.

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