Ultomiris (ravulizumab-cwvz) / AstraZeneca, Xencor - LARVOL DELTA

Comparative Efficacy of Zilucoplan Versus Intravenous Immunoglobulin, Eculizumab, and Ravulizumab Using Matching-Adjusted Indirect Comparisons. (PubMed, Neurol Ther) - "In this analysis, zilucoplan was associated with a significantly higher magnitude of clinically meaningful improvement in QMG and MG-ADL scores compared to IVIg and two C5 inhibitors, eculizumab and ravulizumab. In the absence of head-to-head clinical data, these findings provide additional evidence to assist with treatment decisions in this setting."

Journal • CNS Disorders • Immunology • Myasthenia Gravis

NMOSD: An Unexpected Paraneoplastic or Autoimmune Occurrence in Setting of Metastatic Neuroendocrine Tumor (ACG 2026) - "Therapy was subsequently started with ravulizumab, a monoclonal antibody that inhibits terminal complement activity which led to significant improvement in her neurological symptoms...Although initially suspected to be radiation therapy related, the patientâs TM was ultimately diagnosed by neurology as NMOSD which could either be paraneoplastic or autoimmune and related to history of Sjogrenâs disease. This case highlights the value of maintaining a broad list of differential diagnoses and utilizing a multidisciplinary approach to the management of oncologic and autoimmune diagnoses."

Metastases • CNS Disorders • Gastric Cancer • Gastroenterology • Gastrointestinal Disorder • Gastrointestinal Neuroendocrine Tumor • Immunology • Neuroendocrine Tumor • Neuromyelitis Optica Spectrum Disorder • Oncology • Sjogren's Syndrome • Solid Tumor • Urinary Incontinence

Atypical hemolytic uremic syndrome: pathophysiology, clinical presentation, and treatment strategies. (PubMed, Child Kidney Dis) - "The introduction of complement inhibitors, such as eculizumab and ravulizumab, has significantly improved clinical outcomes by reducing recurrence and preserving renal function. This review aimed to examine the pathophysiology, clinical manifestations, and treatment strategies of aHUS. Early and targeted complement inhibition is essential for preventing irreversible kidney damage and optimizing outcomes, particularly in children and transplant recipients."

Journal • Review • Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Pediatrics • Renal Disease • Thrombocytopenia • Transplantation

BEST-NMOSD: Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab, and Eculizumab in NMOSD (clinicaltrials.gov) - P4 | N=540 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Real-World Effectiveness of Ravulizumab in C5 Inhibitor-Naïve Patients with Atypical Haemolytic Uremic Syndrome Associated with an Autoimmune Trigger (ACR Convergence 2026) - No abstract available

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Immunology

Complement C5 inhibition after kidney transplantation – A national single-center experience from Slovenia (TTS 2026) - " We retrospectively reviewed medical records of kidney transplant recipients treated with eculizumab/ravulizumab at the University Medical Centre Ljubljana, including their clinical, laboratory, and histopathological characteristics, as well as treatment outcomes...One patient, eight years after transplantation, received eculizumab for one month for chronic active AMR without TMA, in addition to intensified immunosuppression including daratumumab... C5 inhibition may be effective in kidney transplant recipients with primary aHUS, de novo TMA (with or without AMR), and in selected cases of C3 nephropathy."

Clinical • Antibody-mediated Rejection • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Complement-mediated Rare Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Infectious Disease • Nephrology • Transplantation

A Case of Catastrophic Antiphospholipid Syndrome Complicated by Aortitis and Treated With Ravulizumab. (PubMed, Int J Rheum Dis) - No abstract available

Journal • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders

Efficacy and Safety of Ravulizumab in Chinese Adults Participants With Generalized Myasthenia Gravis (gMG) (clinicaltrials.gov) - P3 | N=20 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Immunology • Myasthenia Gravis

Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity Study of Ravulizumab in Chinese Adults With Neuromyelitis Optica Spectrum Disorder (NMOSD) (clinicaltrials.gov) - P3 | N=19 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

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

Current practices in antibiotic prophylaxis for patients on complement inhibitors: a multicenter survey across ERN ERKnet centers. (PubMed, Clin Kidney J) - "Complement inhibitors such as eculizumab and ravulizumab are increasingly used to treat rare complement-mediated diseases...In pediatric settings, phenoxymethylpenicillin and amoxicillin were most commonly used, whereas adult regimens included penicillin or fluoroquinolones for those with allergies...Based on these findings, we propose consensus guidance to support harmonized, risk-adapted prophylaxis strategies across pediatric and adult populations. These guidance statements aim to address an important unmet need in infection prevention among complement-inhibited patients."

Journal • Allergy • Complement-mediated Rare Disorders • Immunology • Infectious Disease • Nephrology • Pediatrics • Rare Diseases • Renal Disease • Transplantation

aHUS-OPTIMUM: Ravulizumab Outcomes in Polish Patients With aHUS (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2030 ➔ Sep 2029 | Trial primary completion date: Dec 2030 ➔ Sep 2029

Trial completion date • Trial primary completion date • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology

Influenza A(H1N1) triggered atypical hemolytic uremic syndrome in a child with homozygous CD46 variant successfully treated with ravulizumab: a case report. (PubMed, CEN Case Rep) - "This case underscores the importance of early C5 inhibition in complement-mediated thrombotic microangiopathy associated with defects in membrane-bound complement regulators, in which therapeutic plasma exchange may have limited efficacy. It also highlights how infections can act as triggers that unmask underlying genetic susceptibility."

Journal • Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Influenza • Nephrology • Pain • Pediatrics • Renal Disease • Respiratory Diseases • Thrombocytopenia • CD46

Neuroimmunological overlap syndromes in optic neuritis, myelitis, and connective tissue diseases. (PubMed, Front Neurol) - "Four biologics inebilizumab (B-cell depletion), satralizumab (IL-6 blockade), and eculizumab/ravulizumab (complement inhibition) are approved for AQP4-IgG-positive NMOSD. Neuroimmunological overlap syndromes should be conceptualized as a unified neuroimmune continuum rather than discrete diseases. Priority research includes biomarker validation, head-to-head comparative cohorts, and randomized trials for MOGAD and CTD-associated neuroinflammation."

Journal • Review • CNS Disorders • Immunology • Inflammation • Neuromyelitis Optica Spectrum Disorder • Ocular Inflammation • Ophthalmology • Optic Neuritis • Rheumatology • GFAP • IFNG • IL17A • TNFA

Ravulizumab rescue therapy in a refractory AQP4-positive neuromyelitis optica attack with extensive encephalomyelitis. (PubMed, Rev Neurol (Paris)) - No abstract available

Journal • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Update on Phase III trial of ULTOMIRIS (ravulizumab-cwvz) in adults and adolescents with thrombotic microangiopathy after hematopoietic stem cell transplant (AstraZeneca) - "Vincent Ho, MD...said: 'HSCT-TMA is a serious complication after stem cell transplant with high rates of associated morbidity and mortality and for which effective therapy remains an area of great unmet need. Conducting a global, randomized trial in this complex, life-threatening, post-transplant condition is exceedingly difficult. While the Phase III trial in adults and adolescents did not meet the primary endpoint, the results add new, important insights to advance the field. Continued evaluation of these data together with results collected from recent, real-world experience will further advance clinical understanding and treatment of this complex transplant complication.'"

Media quote

Study of Ravulizumab in Pediatric Participants With Primary IgAN (clinicaltrials.gov) - P3 | N=36 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | N=24 ➔ 36 | Trial completion date: Nov 2029 ➔ Apr 2030 | Trial primary completion date: Jul 2028 ➔ Nov 2028

Enrollment change • Trial completion date • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Nephrology • Pediatrics • Renal Disease • Vasculitis

Terminal complement inhibition is associated with renal, hematologic, and thrombotic complications during septic shock: A global propensity score-matched cohort study. (PubMed, J Crit Care) - "In septic shock, terminal complement inhibition was associated with increased renal, hematologic, and thrombotic complications without a significant difference in short-term mortality. These findings identify a clinically vulnerable, currently uncommon but increasingly relevant patient population."

Journal • Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Septic Shock • Thrombocytopenia • Thrombosis

Acute neurologic clinical manifestations and outcomes in children with thrombotic microangiopathies in paediatric intensive care units. (PubMed, Eur J Pediatr) - "In our cohort, almost one-third of participants developed neurological manifestations, most of them severe, during a PICU admission for TMA, and this was associated with prolonged recovery times and an increased need for supportive interventions. This warrants close neurological surveillance by PICU staff for the timely introduction of protective measures, although the impact of such measures on mortality and long-term outcomes needs further research."

Journal • Observational data • Atypical Hemolytic Uremic Syndrome • CNS Disorders • Critical care • Epilepsy • Pediatrics

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

Xencor…announced its agreement with Alexion Pharma International Operations Limited, an Irish limited company ('Alexion'), to resolve a commercial dispute related to U.S. royalties on Ultomiris (ravulizumab-cwvz) (the 'Settlement Agreement') (Businesswire) - "Under the Settlement Agreement, Xencor will receive $105 million in two equal payments, the first $52.5 million payment is anticipated in August 2026 and the second $52.5 million payment on the one-year anniversary of the executed Settlement Agreement, and Alexion will have no further obligation to pay royalties on U.S. sales of Ultomiris. Xencor expects to continue receiving royalties on ex-U.S. sales of Ultomiris under the existing terms of their license agreement."

Commercial • Atypical Hemolytic Uremic Syndrome • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria

High-level results from the ALXN1210-TMA-313 Phase III clinical trial showed that Ultomiris (ravulizumab) did not achieve statistical significance for the primary endpoint of event-free survival through 26 weeks compared to placebo in adults and adolescents (aged 12 years or older) with thrombotic microangiopathy after haematopoietic stem cell transplant (HSCT-TMA). (AstraZeneca Press Release) - "In paediatric patients with HSCT-TMA, the ALXN1210-TMA-314 open-label Phase III trial of Ultomiris demonstrated clinically meaningful overall survival of 87.2% at 26 weeks and 73.4% at 52 weeks, as previously disclosed. Alexion, AstraZeneca Rare Disease is advancing regulatory filings for Ultomiris in paediatric patients with HSCT-TMA, based on these results and data from ALX-TMA-502, an external control study, which further supports clinically meaningful benefit on overall survival...The safety profile observed across the ALXN1210-TMA-313 and ALXN1210-TMA-314 trials was consistent with the known safety profile of Ultomiris and with that seen in patients undergoing HSCT."

Filing • P3 data • Hematological Disorders • Immunology • Transplantation

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

ARTEMIS: Ravulizumab to Protect Patients With CKD From CSA-AKI and MAKE (clinicaltrials.gov) - P3 | N=555 | Terminated | Sponsor: Alexion Pharmaceuticals, Inc. | Completed ➔ Terminated; The ALXN1210-CSA-AKI-318 trial was discontinued on 29-Apr-2026 due to lack of efficacy in this overall study universe / patient population.

Adverse events • Trial termination • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Heart Failure • Nephrology • Renal Disease • CST3

Clinical similarity in cost-comparison evaluations: a systematic review of current methods in NICE appraisals and the development of a framework for the formal assessment of clinical similarity. (PubMed, BMJ Open) - "Interpretations of statistically non-significant ITC results are inconsistent within individual CCEs and across appraisals. Implementation of the presented recommendations and framework would improve the consistency and robustness of CCEs."

HEOR • Journal • NICE • Reimbursement • Review • US reimbursement • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria