Results from 2 late-stage trials evaluating generalized myasthenia gravis therapies indicated both drugs, rozanolixizumab and zilucoplan, have potential as targeted treatment options.
Data on 2 investigative therapies for generalized myasthenia gravis (gMG) were published this month in The Lancet Neurology.
The therapies, rozanolixizumab and zilucoplan, are currently under regulatory review in the United States, Europe, and Japan. The phase 3 trials showed both therapies have potential as targeted treatment options, with individual mechanisms of action targeting the underlying disease pathology that causes gMG. gMG is a rare, chronic, heterogeneous, and unpredictable autoimmune disease marked by dysfunction and damage at the neuromuscular junction.
Rozanolixizumab was evaluated for efficacy and safety in the MycarinG study, which included 200 patients with acetylcholine receptor autoantibody-positive (AChR-Ab+) or muscle-specific tyrosine kinase autoantibody-positive (MuSK-Ab+) gMG.1
The RAISE study examined the efficacy and safety of zilucoplan in 174 dult patients with mild to severe AChR-Ab+ gMG.2
Both studies, which were funded by the drugmaker UCB, looked at the impact of the therapies on the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL).
The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and functional activities related to ADLs. Each of the items is scored from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24. Higher scores indicate greater severity of symptoms.
In the MycarinG study, rozanolixizumab showed demonstrated statistically significant and clinically meaningful improvements in MG-specific outcomes in patients with MuSK-Ab+ or AChR-Ab+ gMG at 2 different doses. The Myasthenia Gravis Symptoms PRO, a measure used to assess symptom severity and impact of MG on patient lives, including physical fatigue which is not covered in other MG clinical outcome assessments, demonstrated statistically significant results vs placebo.
In the RAISE study, zilucoplan showed rapid efficacy, with consistent, sustained, clinically meaningful and statistically significant improvements versus placebo from baseline to week 12 in both patient and clinician-reported endpoints.
Both rozanolixizumab doses were generally well tolerated with similar occurrences of treatment-emergent adverse events (TEAEs) between both doses. The most frequently reported TEAEs were headache, diarrhea, and pyrexia. A higher incidence of headache was reported in the rozanolixizumab groups versus placebo, with most cases mild to moderate and severe cases generally managed with non-opioid analgesics. Treatment discontinuation rates due to TEAEs were low.
Zilucoplan was generally well tolerated with a favorable safety profile. The most frequently reported TEAEs in the zilucoplan group were injection site bruising, headache, diarrhea, and (worsening of) MG. Incidences of serious TEAEs and serious infections were similar in both group.
References
1. Bril V, Drużdż A, Grosskreutz J, et al. Efficacy and safety of rozanolixizumab in patients with generalised myasthenia gravis: a randomised, double-blind, placebo-controlled, adaptive Phase 3 study MyCarinG study. Lancet Neurol. 2023; 22(50);383-394. doi:10.1016/S1474-4422(23)00077-7
2. Howard J, Bresch A, Genge S, et al. Efficacy and safety of zilucoplan in patients with generalised myasthenia gravis: A randomised, double-blind, placebo-controlled, Phase 3 study (RAISE). Lancet Neurol. 2023;22(50);395-406. doi: 10.1016/S1474-4422(23)00080-7
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