Zilucoplan Study on Myasthenia Gravis

Researchers have found that a non-FDA-approved drug, Zilucoplan, a complement inhibitor, showed promise in a phase 2 study of patients with acetylcholine receptor antibody–positive myasthenia gravis. The study has been published in JAMA Neurology.

Myasthenia gravis (MG), an autoimmune disease that affects synaptic transmission at the neuromuscular junction, is classified into different subtypes on the basis of type of antibodies and manifestation of the disease, such as generalized or ocular myasthenia.

Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life.

The researchers conducted a study to evaluate the clinical effects of zilucoplan, a subcutaneously (SC) self-administered macrocyclic peptide inhibitor of complement component 5, in a broad population of patients with moderate to severe gMG.

In order to test the efficacy of zilucoplan in moderate to severe AChR antibody–positive patients with gMG, researchers conducted a manufacturer-funded, phase 2, randomized, double-blind, placebo-controlled, multicenter clinical trial. The study included 44 patients randomized to daily self-injection of placebo, 0.1 mg/kg zilucoplan, or 0.3 mg/kg zilucoplan for 12 weeks. The primary outcome measure was change in quantitative myasthenia gravis (QMG) score and in MG activities of daily living (MG-ADL) score.

Zilucoplan yielded rapid, clinically meaningful, statistically significant, and sustained improvements in the primary and key secondary end points. Near-complete complement inhibition was associated with a faster onset and greater magnitude of benefit than submaximal complement inhibition, and favorable safety and tolerability were observed.

Patients treated with either dose of zilucoplan had significant improvement in both QMG and MG-ADL compared with placebo recipients. The higher-dose recipients had earlier, more sustained improvements than the lower-dose recipients. Mild adverse effects were reported which were not considered related to treatment.

The authors concluded that Zilucoplan yielded rapid, meaningful, and sustained improvements over 12 weeks in a broad population of patients with moderate to severe AChR-Ab–positive gMG. Near-complete complement inhibition appeared superior to submaximal inhibition. The observed safety and tolerability profile of zilucoplan was favorable.

For further reference log on to:

• Howard JF Jr et al. Clinical effects of the self-administered subcutaneous complement inhibitor zilucoplan in patients with moderate to severe generalized myasthenia gravis: Results of a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial. doi:10.1001/jamaneurol.2019.5125