Zilbrysq (zilucoplan)

The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor.

The safety and efficacy of zilucoplan were evaluated in:

• a 12-week multicentre, randomised, double-blind placebo-controlled study MG0010 (RAISE) and
• an open-label extension study MG0011 (RAISE-XT) (Open label extension studies usually follow a double blind randomised placebo controlled trial of a new drug after which patients have the option of enrolling in the extension study. In the extension phase, there is no blinding, so both patients and investigators are aware that all patients have been given the drug). Open label extension studies aim to give insight into the safety and tolerability of the drug in the long term. 

In the RAISE study, a total of 174 patients were enrolled, who were at least 18 years of age, had anti-AChR antibody positive gMG, MGFA Class II-IV (mild to severe), a Myasthenia Gravis Activities of Daily Living (MGADL) Score of ≥6 and a Quantitative Myasthenia Gravis (QMG Score) of ≥12. The primary endpoint was the change from baseline to Week 12 in MGADL total score. MG-ADL is an 8-item patient reported outcome measure assessing impact of gMG on daily function of signs and symptoms

Two hundred patients were enrolled In the open-label extension RAISE-XT study. These patients had completed either the placebo-controlled Phase 2 (MG0009) or Phase 3 RAISE (MG0010) studies. The RAISE-XT/MG0011 study was primarily a safety and tolerability study which was not randomized or placebo-controlled, therefore efficacy was inferred. Efficacy endpoints were: a change-from-baseline in MGADL, QMG, MGC (Myasthenia Gravis Composite score) and the myasthenia gravis quality of life-15 revised (MG-QoL15r) score at Week 12 of the open-label extension period. The results of this open label study demonstrated sustained efficacy through to Week 60.