UCB Zilucoplan is the first once-daily subcutaneous (SC), targeted peptide inhibitor of complement component 5 (C5 inhibitor)2. It is the only once-daily gMG target therapy for self-administration by adult patients with anti-AChR antibody-positive gMG.
As a complement C5 inhibitor, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted mechanism of action.2 Benefits of self-administered treatment compared with intravenously administered treatments 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.2
The FDA approval of zilucoplan1 is supported by safety and efficacy data from the RAISE study (NCT04115293), published in The Lancet Neurology in May 2023.2 The RAISE study was a multi-center, phase 3, randomized, double-blind, placebo-controlled study to assess 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. The study demonstrated that zilucoplan delivered rapid, consistent, and statistically significant benefits in different patient-and-clinician reported outcomes at week 12 in a broad population of adult patients with mild-to-severe anti-AChR-antibody positive gMG. The most common adverse reactions (10%) in patients with gMG were injection site reactions, upper respiratory tract infection, and diarrhea.
'For people with gMG, the unpredictable nature of the severity and frequency of symptoms can be debilitating and can have a substantial impact on many aspects of their day-to-day lives. In addition to muscle weakness, people living with gMG experience fatigue, affecting their overall quality of life,' said
gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterized by dysfunction and damage at the neuromuscular junction (NMJ).4,5,6 Several factors are understood to be drivers of gMG disease pathology, including the complement cascade, immune cells and pathogenic Immunoglobulin G (IgG) autoantibodies.7
In anti-AChR antibody-positive gMG, pathogenic AChR autoantibodies (IgG1 and IgG3) initiate the classical complement pathway, leading to the cleavage of C5 and the MAC (membrane attack complex) formation, damage to the NMJ, loss of AChRs and subsequent impaired synaptic transmission.6,8,9 Preventing MAC formation reduces damage to the post-synaptic membrane, reduces disruption of ionic channel conductance and helps to preserve neuromuscular transmission.8 MG has a global prevalence of 100-350 cases per every 1 million people.5
'This is an important development for the community because, with more FDA-approved treatments for generalized myasthenia gravis, physicians have additional tools to treat this disease in individualized ways that are the right fit for each individual patient,' said
With the approval of zilucoplan, alongside the company's neonatal Fc receptor (FcRn) blocker RYSTIGGO (rozanolixizumab-noli), which was approved earlier this year by the FDA under Priority Review designation for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive, UCB's portfolio provides healthcare professionals the option of addressing either complement activation or pathogenic auto-antibodies for appropriate patients.3,10
'With the FDA approval for zilucoplan, we are very proud and excited to expand our support to the gMG community. Following the FDA approval and strong momentum with our FcRn inhibitor rozanolixizumab-noli and with our tailored patient support services and commitment to widespread access, I am confident that UCB is the only company with a portfolio of two targeted therapies with different mechanisms of action and the experience to deliver truly individualized transformational patient value to people living with this often debilitating rare disease' said
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. The MG-ADL is an eight-item patient-reported outcome measure assessing MG symptoms and functional activities related to activities of daily living.11 These include activities such as breathing, talking, swallowing, and being able to rise from a chair.12 Each of the items is scored, from 0 (normal) to 3 (most severe), providing a total MG-ADL score ranging from 0 to 24, where higher scores indicate greater severity of symptoms.
The efficacy of zilucoplan was also measured, as a secondary endpoint, using the Quantitative Myasthenia Gravis (QMG) total score which is a 13-item categorical grading system that assesses muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment.
At week 12, treatment with zilucoplan demonstrated a statistically significant improvement from baseline compared to placebo for MG-ADL total score and QMG total score. Other secondary endpoints included the proportion of patients with improvements of at least 3 and 5 points in the MG-ADL total score and QMG total score, respectively, at week 12 without rescue therapy.
'Until now, people living with gMG have only had access to C5 therapy intravenously, which can be inconvenient and time consuming. Now, with the option of zilucoplan, a self-administered once-daily, subcutaneous targeted complement C5 inhibitor, we hope a broad population of mild-to-severe adult patients with AChR-antibody-positive gMG will be able to have greater independence' said
About zilucoplan
Zilucoplan is a once-daily, SC, self-administered peptide inhibitor of complement component 5 (C5 inhibitor). As the only once-daily gMG target therapy for self-administration by adult patients with anti-AChR antibody-positive gMG, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted mechanism of action.2
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Zilucoplan is currently under review by the
Orphan designation was granted by the FDA in 2019 to zilucoplan for the treatment of myasthenia gravis.
About generalized Myasthenia Gravis (gMG)
gMG is a rare autoimmune disease with a global prevalence of 100-350 cases per every 1 million people.5 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.4,16
In MG, pathogenic autoantibodies can impair synaptic transmission at the neuromuscular junction (NMJ) by targeting specific proteins on the post-synaptic membrane.17 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.
About the RAISE study2
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.
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. Other secondary efficacy outcomes, time to first receipt of rescue therapy over 12 weeks, the proportion of patients with minimal symptom expression (MSE) (defined as MG-ADL of 0 or 1 without rescue therapy), the proportion of patients with a 3-point reduction in MG-ADL without rescue therapy and the proportion of patients 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-noli
In addition to zilucoplan, UCB's gMG portfolio includes the FDA-approved medicine RYSTIGGO (rozanolixizumab-noli), a subcutaneously infused monoclonal antibody targeting the neonatal Fc receptor (FcRn).9
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Rozanolixizumab is currently under review by the
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Email: antje.witte@ucb.com
About UCB
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