Zilucoplan is the first once-daily subcutaneous (SC), targeted peptide inhibitor of complement component 5 (C5) inhibitor for gMG, and the only C5 inhibitor approved for self-administration by adult patients with AChR antibody-positive gMG.
As a C5 inhibitor, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted dual mechanism of action.2 Benefits of SC self-injection can include reduced traveling time to and from hospitals, decreased interference with work obligations, and increased independence.
Unlike monoclonal antibody C5 inhibitors, as a peptide, zilucoplan can be used concomitantly with intravenous immunoglobulin and plasma exchange, without the need for supplemental dosing.
As included within the zilucoplan EU Summary of Product Characteristics, the most frequently reported adverse reactions were injection site reactions (injection site bruising (13.9%) and injection site pain (7.0%)) and upper respiratory tract infections (nasopharyngitis (5.2%), upper respiratory tract infection (3.5%) and sinusitis (3.5%)).1
European approval of zilucoplan follows approvals by the
gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterized by dysfunction and damage at the neuromuscular junction (NMJ).7,8,9 Several factors are understood to be drivers of gMG disease pathology, including the complement cascade, immune cells and pathogenic Immunoglobulin G (IgG) autoantibodies10.
In AChR antibody-positive gMG, pathogenic AChR autoantibodies (IgG1 and IgG3) initiate the classical complement pathway, which, together with the alternative and lectin complement pathways, converge at C5, leading to MAC (membrane attack complex) deposition, damage to the NMJ, loss of AChRs and subsequent impaired synaptic transmission.9,11 Preventing MAC formation reduces damage to the post-synaptic membrane, reduces disruption of ionic channel conductance and helps to preserve neuromuscular transmission.11
MG has a global prevalence of 100-350 cases per every 1 million people.8
Alongside approval of zilucoplan, UCB's neonatal Fc receptor (FcRn) blocker rozanolixizumab recently received a positive opinion from the
'With the
The approval of zilucoplan from the EC is valid in all EU member states, as well as in the European Economic Area (EEA) countries
UCB is committed to making zilucoplan available to patients as quickly as possible and anticipates European availability will commence in the first quarter of 2024.
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
About zilucoplan
Zilucoplan is a once-daily SC, self-administered peptide inhibitor of complement component 5 (C5) inhibitor. As the only self-administered C5 inhibitor targeted therapy for gMG, zilucoplan may inhibit complement-mediated damage to the neuromuscular junction through its targeted mechanism of action.2
In
Zilucoplan is currently under review by the
About Generalized Myasthenia Gravis (gMG)
gMG is a rare autoimmune disease with a global prevalence of 100-350 cases per every 1 million people.8 People living with gMG can experience a variety of symptoms, including severe muscular weakness that can result in double vision, drooping eyelids, difficulty with swallowing, chewing and talking, as well as life-threatening weakness of the muscles of respiration.7,13
In MG, pathogenic autoantibodies can impair synaptic transmission at the neuromuscular junction (NMJ) by targeting specific proteins on the post-synaptic membrane.14 This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction. gMG can occur in any race, gender or age.7,13
About the RAISE study2
The RAISE study (NCT04115293) was a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to confirm the efficacy, safety profile, and tolerability of zilucoplan in adult patients with anti-acetylcholine receptor (AChR) antibody-positive gMG. Patients were randomized in a 1:1 ratio to receive daily subcutaneous (SC) injections of 0.3 mg/kg zilucoplan or placebo for 12 weeks.2
The primary endpoint for the RAISE study was change from baseline to Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score.2
Secondary endpoints included change from baseline in the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Quality of Life 15 revised (MG-QoL15r) score from baseline to Week 12, time to first rescue therapy, the proportion of patients with minimal symptom expression (MSE) (defined as MG-ADL of 0 or 1 without rescue therapy), the proportion with a 3-point reduction in MG-ADL without rescue therapy and the proportion with a 5-point reduction in QMG without rescue therapy, all measured at Week 12. Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs). Patients who completed the RAISE trial had the possibility to enter the open-label extension study, RAISE-XT (NCT04225871).2
About Rozanolixizumab
Rozanolixizumab is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.15 It has been designed to block the interaction of FcRn and Immunoglobulin G (IgG), accelerating the catabolism of antibodies and reducing the concentration of pathogenic IgG autoantibodies.15
In
In
In
Rozanolixizumab is also currently under review by the Center of Drug Evaluation of the
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