Zilbrysq (zilucoplan) / UCB - LARVOL DELTA

Human in vitro neuromuscular junction model to functionally dissect the pathogenic mechanism of anti-AChR autoantibody-positive myasthenia gravis. (PubMed, BMC Pharmacol Toxicol) - "These findings offer a mechanistic rationale for the observed clinical response in patients with anti-AChR autoantibody-positive myasthenia gravis treated with C5 inhibitors. The in vitro neuromuscular junction model provides a robust platform for studying the mechanistic pathways of complement-mediated damage and evaluating therapeutic interventions for myasthenia gravis."

Journal • Preclinical • CNS Disorders • Immunology • Myasthenia Gravis

Real-world data on breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria treated with proximal and terminal complement inhibitors. (ASH 2025) - "Four patients were treated with factor D inhibitor danicopan(n=3) or iptacopan (n=1) concurrently with ravulizumab.A total of 49 BTH events were identified; while on eculizumab (26 events, 12 patients), ravulizumab (14events, 7 patients), ravulizumab and danicopan (6 events, 3 patients), pegcetacoplan (1 event, 1 patient),zilucoplan (2 events, 2 patients), and no events while on iptacopan. Twelve BTH events were incidentally detected during routine CIadministration; more frequent lab draws may be beneficial for patients with chronic hemolysis. Moredata is needed to understand the BTH rates of different CIs and guide clinicians in BTH management."

Clinical • Real-world • Real-world evidence • Anemia • Aplastic Anemia • Breast Cancer • Complement-mediated Rare Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Solid Tumor • CD55 • CD59 • HP

Discovery of Zilucoplan: A Complement C5 Inhibitor for Treatment of Anti-Acetylcholine Receptor (AChR) Antibody-Positive Generalized Myasthenia Gravis (gMG). (PubMed, J Med Chem) - "In Ribosome Display and Related Technologies: Methods and Protocols; Douthwaite, J. A., Jackson, R. H., Eds.; Springer: New York, 2012; pp 367-390.) against C5 and approved for the treatment of gMG. We highlight the key steps and rationale behind the peptide medicinal chemistry optimization of the initial screening hits, that led to improved potency, stability, and pharmacokinetic properties."

Journal • CNS Disorders • Myasthenia Gravis

Effectiveness and Safety of Zilucoplan Treatment for French Patients With Myasthenia Gravis Over 3 Months (clinicaltrials.gov) - P=N/A | N=55 | Recruiting | Sponsor: Centre Hospitalier Universitaire de Nice | Not yet recruiting ➔ Recruiting | Trial primary completion date: Nov 2025 ➔ Feb 2026

Enrollment open • Trial primary completion date • CNS Disorders • Myasthenia Gravis

Early real-life experience on Zilucoplan for generalized myasthenia gravis: ZILU25 multicenter observational study. (PubMed, J Neurol Sci) - "Zilucoplan was well-tolerated and effective in most patients with AChR-positive gMG. A clinical meaningful effect was reported since the first week and was sustained after 24 weeks. Further studies are needed to confirm these preliminary real-life data."

Journal • Observational data • CNS Disorders • Immunology • Myasthenia Gravis

Complement Inhibitors in Generalized Myasthenia Gravis: Comparison of Administration Schedules, Efficacy, and Safety. (PubMed, J Clin Med) - "Background: Eculizumab, Ravulizumab, and Zilucoplan are inhibitors of terminal complement protein C5 (C5IT) approved for the treatment of generalized Myasthenia Gravis (gMG). Most of the reported adverse events were mild to moderate; the more severe events included one case of Stevens-Johnson syndrome (Ravulizumab) and episodes of pneumonia (Eculizumab, Ravulizumab). The comparison of C5IT did not bring out significant differences in terms of clinical efficacy and safety, representing a valid therapeutic option when traditional therapies fail to control disease symptoms."

Journal • CNS Disorders • Infectious Disease • Myasthenia Gravis • Pneumonia • Respiratory Diseases • Steven-Johnson Syndrome

Complement C5 Inhibitor (Anti-C5) and Neonatal Fc Receptor Antagonist Anti-FcRn in Myasthenia Gravis at University Public Hospitals of Paris, France (AP-HP): What Is the Market Share of These New Treatments? (ISPOR-EU 2025) - "This falls to 352 DDD in 2023 with the arrival of ravulizumab, then goes to 1861 DDD in 2024 despite the eculizumab biosimilar. Prescriptions are tending towards efgartigimod-IV, though ravulizumab continues to hold an important place, particularly in long-stay patients, where it replaces eculizumab and generates the highest costs. However, this trend could change with the arrival of subcutaneous forms available in community pharmacies (zilucoplan, efgartigimod-SC and rozanolixizumab), potentially modifying therapeutic practices and hospital costs."

Clinical • CNS Disorders • Myasthenia Gravis

Costs and Number Needed to Treat (NNT) to Achieve Improvements With C5 Inhibitors in Generalized Myasthenia Gravis From the Japanese Healthcare Perspective: A Network Meta-Analysis (ISPOR-EU 2025) - P3 | "Zilucoplan showed similar or lower NNTs (0.31-0.48) and CPIO (M¥10.68-M¥16.41) compared to ravulizumab (NNT: 0.50-0.59; CPIO: M¥23.61-M¥27.83) and eculizumab (NNT: 0.30-0.52; CPIO: M¥19.32-M¥33.68) across all CFB endpoints. Furthermore, zilucoplan demonstrated superior cost-benefit, requiring lower treatment costs to achieve each improved outcome."

Retrospective data • CNS Disorders • Myasthenia Gravis

Management of Myasthenic Crisis and Emerging Roles of Molecularly Targeted Therapies: A Narrative Review. (PubMed, Neurol Int) - "Conventional MCr treatments-such as plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and intravenous methylprednisolone (IVMP)-remain standard treatments; however, they present significant limitations, including delayed onset of action, adverse effects, and inconsistent efficacy...We review published case reports involving FcRn inhibitors (efgartigimod, efgartigimod-SC, rozanolixizumab) and complement inhibitors (eculizumab, ravulizumab, zilucoplan), highlighting their rapid onset of action and safety profiles in MCr...We also discuss strategic considerations for therapy selection, including antibody subtype, coexisting autoimmune conditions, genetic factors, and transition to long-term maintenance. Though the current evidence is promising, large-scale randomized studies are needed to establish definitive roles for these therapies in MCr management."

Journal • Review • CNS Disorders • Critical care • Immunology • Myasthenia Gravis • Respiratory Diseases

A total of 18 abstracts will be presented at AANEM and the MGFA scientific session, highlighting UCB's dedication to driving advancements in gMG treatment. (PRNewswire) - "These presentations will cover data on rozanolixizumab and zilucoplan, including new insights on corticosteroid-sparing strategies and quality of life, and long-term safety and effectiveness data. Additionally, insights from a real-world study on user characteristics and adherence patterns from the HumaMG app will be shared, reinforcing UCB's commitment to improving gMG management."

Clinical data • Myasthenia Gravis

Safety profile of complement C5 inhibitors and FcRn inhibitors in the treatment of myasthenia gravis: analysis of the FAERS database and disease-gene interaction network. (PubMed, Front Immunol) - "To integrate pharmacovigilance and network pharmacology methods for a comprehensive analysis of the potential adverse reactions of complement C5 inhibitors (eculizumab, ravulizumab, zilucoplan) and neonatal Fc receptor (FcRn) inhibitors (efgartigimod, rozanolixizumab), and to explore their toxicity mechanisms, thereby providing a reference for rapidly understanding the safety of these two novel classes of biologics in the treatment of myasthenia gravis (MG). Furthermore, network pharmacology analysis revealed potential mechanisms underlying these adverse reactions. These findings provide valuable insights for monitoring and managing risks during treatment with two novel classes of biologics."

Journal • Cardiovascular • CNS Disorders • Congestive Heart Failure • Dyspepsia • Gastric Cancer • Genito-urinary Cancer • Heart Failure • Hepatology • Immunology • Inflammatory Arthritis • Ischemic stroke • Liver Failure • Myasthenia Gravis • Nephrology • Oncology • Peripheral Arterial Disease • Prostate Cancer • Psoriatic Arthritis • Renal Calculi • Rheumatology • Seronegative Spondyloarthropathies • Solid Tumor

Zilucoplan for Severe gMG Exacerbations (clinicaltrials.gov) - P3 | N=15 | Not yet recruiting | Sponsor: Miriam Freimer

New P3 trial • CNS Disorders • Myasthenia Gravis

SUSTAINED MINIMAL SYMPTOM EXPRESSION IN GENERALISED MYASTHENIA GRAVIS: A 120-WEEK POST HOC ANALYIS OF RAISE-XT (WCN 2025) - P2, P3 | "Zilucoplan demonstrated sustained efficacy, as shown by maintenance of MSE response up to 120 weeks of treatment."

Retrospective data • CNS Disorders • Myasthenia Gravis

TREATMENT GUIDELINES AND COMPLEMENT INHIBITORS (WCN 2025) - "Components available in Japan includes eculizumab, ravulizumab and zilucoplan as C5 inhibitors, efgartigimod and rozanolixizumab as FcRn inhibitors. This prevents the cleavage of C5 into C5a and C5b and thus prevents formation of the membrane attack complex. Zilucoplan also binds to the domain of C5 that corresponds to C5b to block interaction with complement component C6 (dual action)."

CNS Disorders • Myasthenia Gravis

Manifestation of morphea in a patient with myasthenia gravis under therapy with zilucoplan. (PubMed, J Dtsch Dermatol Ges) - No abstract available

Journal • CNS Disorders • Myasthenia Gravis

Enhanced Access to gMG Treatments: UCB Canada Secures pCPA Agreements for ZILBRYSQ and RYSTIGGO (Canada Newswire) - "This significant milestone comes after successfully securing a positive reimbursement recommendation by CDA-AMC and recognition of therapeutic value by INESSS and is a necessary step for securing provincial public reimbursement as the next and final step."

Reimbursement • Myasthenia Gravis

Zilucoplan in myasthenic crisis refractory to conventional treatment: a report of two cases. (PubMed, Acta Neurol Belg) - No abstract available

Journal

A Study to Assess Zilucoplan Concentration in Breast Milk of Healthy Lactating Women (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: UCB Biopharma SRL | Not yet recruiting ➔ Recruiting

Enrollment open

Myasthenia Gravis Treated with Zilucoplan Prior to Extended Transsternal Thymectomy for the Prevention of Myasthenic Crisis: A Case Report (PubMed, Brain Nerve) - "This is the first report on the use of zilucoplan for the prevention of perioperative myasthenic crisis. (Received April 14, 2025; Accepted June 3, 2025, Published August 1, 2025)."

Journal • CNS Disorders • Infectious Disease • Myasthenia Gravis • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • Thymic Carcinoma • Thymoma • Thymus Cancer

Zilucoplan as a fast-acting treatment for severe myasthenic exacerbation: A case series. (PubMed, Rev Neurol (Paris)) - No abstract available

Journal

Neuromuscular junction and the complement system. (PubMed, Int Rev Neurobiol) - "The currently studied anti-complement therapies for MG include eculizumab, zilucoplan, ravulizumab, pozelimab, cemdisiran, gefurilimab, danicopan and few others in the pipeline. Given the risk of Gram-negative septicaemia (especially by meningococcus), patients would need vaccination prior to initiation of treatment and in some countries prophylactic antibiotics during treatment is recommended, although no major safety signatures have been noted in the studies so far. Future studies identifying specific biomarkers might help clinicians select the most appropriate patients who are more likely to respond to complement inhibitory therapies."

Journal • Review • CNS Disorders • Infectious Disease • Meningococcal Infections • Myasthenia Gravis

Unmasking Anti-CASPR2 Syndrome in a Patient Treated for Myasthenia Gravis in the Era of New Treatments. (PubMed, Eur J Neurol) - "This case provides the first evidence of the efficacy of efgartigimod in the treatment of MoS and suggests that FcRn inhibition may be beneficial in IgG4-mediated disorders beyond MG. It also highlights the importance of considering coexisting autoimmune conditions in thymoma, particularly when new symptoms occur under selective immune modulation. Finally, it emphasises the need to understand immunopathological mechanisms when choosing immunomodulatory treatment."

Journal • CNS Disorders • Immune Modulation • Immunology • Movement Disorders • Myasthenia Gravis • Solid Tumor • Thymoma • Thymus Cancer • CNTN

Switching to subcutaneous zilucoplan from intravenous complement component 5 inhibitors in generalised myasthenia gravis: a phase IIIb, open-label study. (PubMed, Ther Adv Neurol Disord) - P3 | "Twenty-six patients enrolled and received zilucoplan; 16 switched from eculizumab and 10 from ravulizumab. ClinicalTrials.gov (NCT05514873); 22 August 2022. https://clinicaltrials.gov/study/NCT05514873."

Journal • P3 data • CNS Disorders • Myasthenia Gravis

Patients denied not one but two beneficial treatments for rare muscle wasting condition - "In the announcement by the National Institute for Health and Care Excellence (NICE) it confirms that Zilucoplan (Zilbrysq) will not be made widely available. The decision is a major setback for those living with the condition, coming just weeks after another treatment for the same condition, efgartigimod, was also rejected...NICE acknowledged that both treatments do ‘improve symptoms and people’s ability to carry out their normal activities’. However, NICE decided that the benefits they offer isn’t currently enough to justify the cost to the NHS."

NICE • Myasthenia Gravis

A comprehensive review of the treatment options in myasthenia gravis. (PubMed, Dis Mon) - "Thymectomy is beneficial for most patients with thymoma and many with antibody positive disease. Choosing the right treatments to maximize benefits and limit adverse effects of the medicines is crucial in this chronic disease."

Journal • CNS Disorders • Myasthenia Gravis • Oncology • Respiratory Diseases • Solid Tumor • Thymoma • Thymus Cancer