Zilbrysq (zilucoplan) / UCB - LARVOL DELTA

Beyond Nature's Blueprint: Macrocyclic Peptides Containing Unnatural Amino Acids in Therapeutic Development. (PubMed, Angew Chem Int Ed Engl) - "In this review, we highlight recent clinical advances-including motixafortide and zilucoplan-and examine how UAAs are deployed to optimize drug-like characteristics across diverse therapeutic areas. We discuss emerging strategies, illustrative case studies, and design principles that collectively support the development of next-generation macrocyclic peptide drugs."

Journal • Review

Regimen-stratified Bayesian model-based meta-analysis of targeted biologics in generalised myasthenia gravis: efficacy comparison, mechanism-level class contrast, and endpoint sensitivity with model-informed trial design. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The study was registered with PROSPERO: CRD420261288549. On MG-ADL, zilucoplan led with the highest Emax (4.8 points; 95% CrI: 4.2-5.4) and largest net benefit (2.5; 2.0-3.1)...Efgartigimod achieved the fastest onset on both scales (≤ 1.6 weeks)...For rozanolixizumab on MG-ADL, snapshot week 26 endpoints were underpowered (65%); integrated endpoints recovered power to 94-95%...Across the multi dimensional treatment-selection framework integrating efficacy, safety, tolerability, and convenience, batoclimab emerged as the highest-ranked agent in all eight clinical priority profiles. These findings provide a pharmacodynamic evidence base for mechanism-guided treatment individualisation and endpoint optimisation in generalised myasthenia gravis."

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

Practical Guidance on Initiating and Switching Targeted Immunotherapies in Generalised Myasthenia Gravis: A German-Austrian Expert Opinion Paper. (PubMed, Eur J Neurol) - "This expert statement provides a practice-oriented framework integrating current evidence and clinical experience to support individualised therapeutic decision-making in gMG."

Journal • CNS Disorders • Immunology • Myasthenia Gravis • Pediatrics

The Drug Reimbursement Evaluation Committee…also recognized the appropriateness for coverage of treatments for myasthenia gravis… (Chosun Biz) - "Handok's 'VYVGART (ingredient name efgartigimod alfa)' and Korea UCB's 'ZILBRYSQ (ingredient name zilucoplan sodium)' were recognized as appropriate for coverage as add-on therapies to standard treatment for adult myasthenia gravis patients who are positive for anti-acetylcholine receptor (AChR) antibodies."

Reimbursement • Immunology • Myasthenia Gravis

Zilucoplan-Associated Morpheaform Skin Changes and Methotrexate and UVA1 Phototherapy. (PubMed, JAMA Dermatol) - No abstract available

Journal

Identifying molecular signatures underpinning treatment responses to novel therapeutics influencing COVID-19 outcomes. (PubMed, J Immunol) - "The ACCORD trial evaluated 3 investigational treatments-bemcentinib, tozorakimab, and zilucoplan-in patients hospitalized with COVID-19, each of which has demonstrated clinical efficacy. These insights support the need for adaptive precision medicine approaches tailored to individual, evolving immune trajectories. Moreover, the immunological mechanisms targeted by these repurposed immunomodulatory therapies may inform treatment strategies across a broader spectrum of immune-mediated diseases beyond COVID-19."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease

Fibrosing Skin Disorder Associated With Zilucoplan. (PubMed, JAMA Dermatol) - No abstract available

Journal • Dermatology

A rare case of morphea following zilucoplan treatment for generalized myasthenia gravis. (PubMed, JAAD Case Rep) - No abstract available

Journal • CNS Disorders • Immunology • Myasthenia Gravis • Scleroderma • Systemic Sclerosis

Case Report: Zilucoplan in refractory myasthenic crisis and its prodromal stages: a novel therapeutic perspective. (PubMed, Front Neurosci) - "Early initiation could prevent progression from iMC to established MC. Larger prospective studies are warranted to define optimal use and timing of Zilucoplan in MG crisis management."

Journal • CNS Disorders • Myasthenia Gravis • Respiratory Diseases

RAISE-XT: Open-Label Extension of Zilucoplan in Subjects With Generalized Myasthenia Gravis (clinicaltrials.gov) - P3 | N=200 | Completed | Sponsor: UCB Biopharma SRL | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Myasthenia Gravis

zilucoplan (Zilbrysq) is accepted for restricted use within NHSScotland (Scottish Medicines Consortium) - "Indication under review: as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. SMC restriction: for adult patients with refractory anti-AChR antibody positive gMG if: (i) the disease has not responded adequately to corticosteroids and at least two other treatments including non-steroidal immunosuppressive therapies (NSISTs) and rituximab, or these options are contraindicated or not tolerated, and (ii) the disease is uncontrolled, as defined by a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of six or greater or a Quantitative Myasthenia Gravis (QMG) score of 12 or greater, and (iii) patients are being considered for, or treated with, maintenance intravenous immunoglobulin (IVIg) or plasma exchange (PLEX)."

Reimbursement • Myasthenia Gravis

Clinical efficacy and cost per improved outcome of treatments for generalized myasthenia gravis: evidence from a network meta-analysis and cost-per-responder analysis. (PubMed, Curr Med Res Opin) - "A de novo NMA was performed using data from Phase III placebo-controlled trials of efgartigimod IV, inebilizumab, nipocalimab, ravulizumab, rozanolixizumab, and zilucoplan, including recently approved therapies. Efgartigimod IV had the lowest CPIO across all QMG and MG-ADL thresholds, significantly lower than almost all other treatments (p < 0.05). Among approved effective biologic therapies for gMG, efgartigimod IV offers a favorable combination of clinical efficacy and economic value."

HEOR • Journal • Retrospective data • CNS Disorders • Myasthenia Gravis

Site-targeted proximal complement C3 inhibition, but not C5 blockade, attenuates neurodegeneration in a mouse model of amyotrophic lateral sclerosis: Implications for failed clinical trials. (PubMed, Neurotherapeutics) - "Failed trials of C5 inhibition - ravulizumab (CHAMPION-ALS) and zilucoplan (ATHLEET/HEALEY ALS Trial), and of systemic C3 inhibition (pegcetacoplan, MERIDIAN) underscore this mechanistic gap. Proximal C3 activation products, not C5a or MAC, are the dominant drivers of complement-mediated neurodegeneration in the hSOD1G93A model of ALS. Site-targeted C3 inhibition may address the mechanistic limitation underlying recent clinical trial failures and represents a translationally justified therapeutic strategy."

Journal • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation

Sustained minimal symptom expression in generalized myasthenia gravis: A 120-week post hoc analysis of RAISE-XT (CNSF 2026) - P2, P3 | "Zilucoplan demonstrated sustained efficacy, evidenced by maintenance of MSE response up to 120 weeks of treatment."

Retrospective data • CNS Disorders • Myasthenia Gravis

Zilucoplan as a rescue therapy in myasthenic crisis: a case description and summary of early report experiences. (PubMed, Acta Neurol Belg) - No abstract available

Journal

Timing of Thymic and Extrathymic Malignancies Relative to Myasthenia Gravis Onset: Oxford Myasthenia Service Cohort (ICNMD 2026) - "Patients receiving targeted therapies (zilucoplan, rituximab, efgartigimod) or regular intravenous immunoglobulin or plasma exchange were excluded. In this cohort, no clear temporal association was observed between MG onset and the occurrence of extrathymic malignancies, providing no strong evidence to support a paraneoplastic relationship outside of thymic malignancy, although interpretation of these findings is limited by small case numbers. The identification of two cases of breast cancer following thymic malignancy highlights the potential risks associated with radiotherapy and radiation exposure during long-term surveillance. This analysis includes patients exposed to conventional immunosuppressive therapies; further work will assess whether treatment dose or duration is associated with extrathymic malignancy risk, and will explore the low incidence of extrathymic malignancy within the thymic malignancy cohort."

Brain Cancer • Breast Cancer • CNS Disorders • Hematological Malignancies • Myasthenia Gravis • Oncology • Solid Tumor • Thymic Carcinoma • Thymus Cancer

Efgartigimod Provides Rapid Clinical Improvements and Reduces Corticosteroid Use in gMG: Initial Results From PREMIER (ICNMD 2026) - "The majority of patients had a history of corticosteroid use (83.9%), and 14.0% had prior use of biologics inhibiting C5 cleavage or neonatal Fc receptors, rituximab or zilucoplan. Initial results from PREMIER demonstrate that patients with gMG treated with efgartigimod improve their symptoms and functional status and reduce corticosteroid use as quickly as Week 4. These benefits were sustained through Week 32. Future data will characterize the long-term experiences of these patients in the real world."

Clinical • CNS Disorders • Immunology • Myasthenia Gravis

Complement Inhibitor Use in an Adolescent With Refractory Juvenile-Onset, Thymomatous, Antibody-Positive Myasthenia Gravis (ICNMD 2026) - "This occurred despite aggressive immunotherapy, including high-dose oral prednisolone (up to 50 mg daily), intravenous immunoglobulin, plasma exchange, and rituximab. This case demonstrates the efficacy and tolerability of complement C5 inhibition with zilucoplan in an adolescent patient with severe, thymoma-associated, AChR-Ab+ refractory gMG. Complement inhibition may represent a valuable therapeutic option in selected cases of refractory JMG, facilitating disease control and substantial reduction in exposure to conventional immunosuppressive therapies."

Cardiovascular • CNS Disorders • Diabetes • Herpes Zoster • Infectious Disease • Myasthenia Gravis • Pulmonary Embolism • Solid Tumor • Thymoma • Thymus Cancer • Varicella Zoster

What We Have Learnt From Comparative Analyses? (ICNMD 2026) - "During the last decade, considerable advances have been made in research and approval of targeted therapies such as complement or neonatal Fc (FcRn) inhibitors which have now entered clinical practice. Literature review and experience from real world use of targeted therapies in MG Clinical experience started with eculizumab for refractory MG and efgartigimod, followed by the approval or ravulizumab and zilucoplan as complement inhibitors, and rozanolixizumab and nipocalimab as FcRn inhibitors. The evidence to guide the choice between anti-complement or anti-FcRn inhibition in severe MG deterioration is still limited. Apart from issues related to autoantibody specificities (anti-acetylcholine vs MuSK), decisions must be made taking into account each patient previous history (particulary the frequency of relapses and need for rescue therapy), comorbidities, and risk of infection, as well as the need to set a strategy as a form of "bridging therapy" or as a..."

CNS Disorders • Immunology • Infectious Disease • Myasthenia Gravis • Respiratory Diseases • Septic Shock

Early First-Week Changes in MG-ADL and MG-QOL-15 During C5 and FcRn-Inhibitors Treatment in Myasthenia Gravis (ICNMD 2026) - "The aim of this study was to assess early daily variations in functional status and quality of life during the first week of treatment with complement (C5) and neonatal Fc receptor (FcRn) inhibitors in patients with gMG. We conducted a retrospective multicenter analysis of 95 patients with gMG receiving complement inhibitors (eculizumab, ravulizumab, zilucoplan) or FcRn inhibitors (efgartigimod, rozanolixizumab). Both C5 and FcRn inhibitors are associated with rapid and clinically meaningful improvements in daily functioning and quality of life within the first week of treatment in gMG. Improvements are detectable as early as day 3 and appear comparable across therapeutic classes, underscoring the fast onset of action of these innovative immunotherapies"

CNS Disorders • Myasthenia Gravis

Usability of Zilucoplan Auto-Injector in Generalised Myasthenia Gravis: A Human Factors Validation Study (ICNMD 2026) - "The data from this human factors validation study demonstrate that the zilucoplan AI is safe and effective for use in patients with gMG. No new hazards or use-related risks were identified. Funding: UCB."

CNS Disorders • Myasthenia Gravis

Real-World Evidence on Utilization and Clinical Outcomes of Efgartigimod in Patients With Myasthenia Gravis (ICNMD 2026) - "Four patients (14.8%) switched to a C5-inhibitor zilucoplan, due to lack of response. In a real-world setting characterized by high disease burden and bulbar involvement, efgartigimod demonstrates significant clinical effectiveness and a steroid-sparing effect. These findings validate the use of FcRn inhibitors outside of clinical trial parameters and support individualized, cycle-based treatment strategies for refractory AChR-Ab+ gMG."

Clinical • Clinical data • HEOR • Real-world • Real-world evidence • CNS Disorders • Myasthenia Gravis • Solid Tumor • Thymoma • Thymus Cancer

Zilucoplan as Rescue Therapy in Refractory Myasthenia Gravis Exacerbations (ICNMD 2026) - "Both patients maintained sustained clinical stability during continued zilucoplan therapy, with no treatment-related adverse events observed. These cases suggest that zilucoplan may induce a rapid, robust, and sustained clinical response in patients with refractory AChR-positive MG during both established myasthenic crisis and impending crisis. Its continuous complement inhibition and easy subcutaneous administration may represent significant advantages in both acute rescue and longer-term disease management."

CNS Disorders • Dysphonia • Gastrointestinal Disorder • Myasthenia Gravis • Respiratory Diseases • Solid Tumor • Thymoma • Thymus Cancer

Individual Item-Level Analyses of Myasthenia Gravis-Specific Outcomes During Zilucoplan Treatment in RAISE and RAISE-XT (ICNMD 2026) - P3 | "Treatment with zilucoplan showed improvements in a greater proportion of patients across individual items in MG-specific outcomes at Week 12 versus placebo. During the extension study, the proportion of patients demonstrating these improvements further increased and were sustained through to Week 120. These data show that treatment with zilucoplan may provide benefit across a broad range of signs and symptoms of MG."

Clinical • CNS Disorders • Myasthenia Gravis

Novel Therapies in Generalized Myasthenia Gravis: Real-World Experience of Zilucoplan in Spain (ICNMD 2026) - "Baseline concomitant treatment consisted of Tacrolimus 3 mg/d, Mycophenolate mofetil 500 mg/12h, Prednisone 15 mg/48h, Pyridostigmine, and Periodic IVIg at 0.7 g/kg every 6 weeks. According to our results, in a real-world setting Zilucoplan is a good novel therapeutic agent for generalized MG AChR-Ab+ in terms of efficacy and safety. Nevertheless, further prospective observational studies are necessary to better define its long-term clinical benefits and safety in MG."

Clinical • Real-world • Real-world evidence • CNS Disorders • Immunology • Infectious Disease • Meningococcal Infections • Myasthenia Gravis • Solid Tumor • Thymoma • Thymus Cancer