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

BEST-NMOSD: Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab, and Eculizumab in NMOSD (clinicaltrials.gov) - P4 | N=160 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P4 trial • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Ravulizumab in the ongoing evolution of aHUS management (ERA 2025) - "Sponsored by Alexion, AstraZeneca Rare Disease."

Complement-mediated Rare Disorders

ISS1.10 How terminal complement inhibition continues to change the landscape of atypical haemolytic uraemic syndrome (aHUS) (ERA 2025) - "Currently approved C5i include eculizumab and ravulizumab, which directly block the terminal complement pathway. Case reports from the faculty will provide a basis for an interactive dialogue with the audience around these and other patient types, and how to optimize their treatment. Finally, the audience will be invited to ask additional questions around how to manage patients with this debilitating and multifaceted disease."

Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology • Pediatrics • Rare Diseases • Renal Disease

2-y crovalimab paroxysmal nocturnal haemoglobinuria (PNH) data for fatigue, a relevant symptom in atypical haemolytic uraemic syndrome (aHUS) and PNH (ERA 2025) - P3 | "Established C5 inhibitors (C5is), such as eculizumab and ravulizumab, are effective for aHUS management but can be burdensome, typically requiring regular intravenous infusions every 2 weeks (eculizumab) or every 8 weeks (ravulizumab). In COMMODORE 2, the improvements in pt-reported fatigue levels observed with crovalimab in the primary treatment period were maintained over a 2-y median follow-up. Accordingly, in COMMODORE 1, fatigue levels remained stable over this same time frame. Overall, these results indicate the long-term benefit that can be achieved with crovalimab."

Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Fatigue • Pain • Paroxysmal Nocturnal Hemoglobinuria

C3 Glomerulonephropathy Overlaps Hereditary Nephritis (ERA 2025) - "Results were compatible with alternative pathway hyperactivation and C3GN was treated with Eculizumab as immunosuppression and prednisone trial had failed...Currently, studies are ongoing for eculizumab and ravulizumab which bind with high affinity to C5 to prevent activation of MAC and C5a...Conclusion Diagnosing patients early, especially with a history of familial hematuria can give a great opportunity for early intervention in HN. C3GN can occur with underlying renal pathology and therapies can range from non-specific immunosuppression to newer complement targeting agents."

Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease • COL4A5

Efficacy and safety of ravulizumab for the maintenance of aHUS remission after kidney transplant (ERA 2025) - " Patients with a clinical diagnosis of aHUS treated with eculizumab for at least three months were switched to ravulizumab. Long-term treatment with ravulizumab proved to be well tolerated and associated with sustained hematologic and renal parameters, and improved quality of life. Furthermore, the close attention to vaccinations status and preventive antibiotic therapy ensured no meningococcal infections during the treatment. Decision which patients required lifelong treatment involved consideration of a wide range of factors."

Clinical • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Infectious Disease • Meningococcal Infections • Nephrology • Renal Disease • Transplantation • HP

A PK/PD Analysis and Population PK Modeling of Ravulizumab Using Data from the Phase 2 Trial in Adults with IgA Nephropathy (SANCTUARY) (ERA 2025) - P2, P3 | "A two-compartment linear PK model described the dose-concentration relationship in adults with IgAN. Our findings describe the PK/PD characteristics of ravulizumab and support the rationale for dose selection in the ongoing phase 3 trial in IgAN (NCT06291376, EU CT 2023- 507851-31-00)."

Clinical • P2 data • PK/PD data • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • IgA Nephropathy • Renal Disease

Safety and mid-term efficacy of switching from Eculizumab to Ravulizumab in a cohort of adult patients with atypical hemolytic uremic syndrome (ERA 2025) - "RVZ represents an important therapeutic option for aHUS patients. Long-term treatment with RVZ was well tolerated and associated with stable renal function and hematological parameters. In addition, the reduced infusion frequency of RVZ reduces the therapeutic burden and, as a result, may improve the quality of life for patients and their caregivers."

Clinical • Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Chronic Kidney Disease • Complement-mediated Rare Disorders • Nephrology • Pediatrics • Thrombocytopenia • HP

Real-world effectiveness of ravulizumab in adults with aHUS who switched to ravulizumab within 3 months of eculizumab treatment (aHUS IMPACT) (ERA 2025) - "This study provides real-world evidence that switching to ravulizumab after short- term eculizumab is achievable in pts with aHUS and can result in significant haematological and renal improvements in this cohort. This was demonstrated by both an early response and continued improvement through 1 year after ravulizumab initiation."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • CFHR3

A Phase 3, Open-Label, Multicenter Study of Ravulizumab in Pediatric Patients With IgA Nephropathy or IgA Vasculitis-Associated Nephritis (ERA 2025) - P3 | "IgAN and IgAVN may lead to kidney failure and need for dialysis or transplant if left untreated. This study aims to characterize the PK, PD, efficacy, and safety of ravulizumab in pediatric patients with IgAN or IgAVN. Data from this study could inform future management of these conditions in the pediatric population."

Clinical • P3 data • Atypical Hemolytic Uremic Syndrome • CNS Disorders • Complement-mediated Rare Disorders • Fibrosis • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Pediatrics • Rare Diseases • Renal Disease • Vasculitis

Terminal complement inhibition in atypical haemolytic uremic syndrome: a single-centre experience (ERA 2025) - " The cohort included 27 patients treated with Eculizumab or Ravulizumab, with a median age at diagnosis of 30 years (IQR: 11–44) and a median follow-up of 13 months (IQR: 9 – 27). In our aHUS cohort, the disease manifested across all age groups, with risk increasing with advancing age. Severe AKI frequently necessitated hemodialysis; however, most patients experienced renal recovery following complement inhibition. Hematological abnormalities and impaired complement function tests were not consistently observed or required for diagnosis."

Clinical • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Complement-mediated Rare Disorders • Immunology • Infectious Disease • Meningococcal Infections • Nephrology • Pediatrics • Thrombocytopenia • Thrombosis • CFH

Atypical haemolytic uremic syndrome in children: the 13-year experience of a tertiary paediatric center (ERA 2025) - "5 children were treated with complement inhibitors (CI) (3 received eculizumab, 1 ravulizumab, and 1 was switched from eculizumab to ravulizumab). In this small cohort of children with aHUS, almost all patients treated with CI achieved a rapid haematological and renal remission with favorable long term kidney outcomes without serious treatment-related adverse effects. Children with MCP variants displayed spontaneous remissions. Discontinuation of CI either with no further treatment or alternative immunosuppression is possible in selected cases based on genetic analyses and anti-CFH antibody status."

Clinical • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Chronic Kidney Disease • Complement-mediated Rare Disorders • Hypertension • Infectious Disease • Pediatrics • Renal Disease • CFHR3

Ravulizumab in atypical haemolytic uraemic syndrome: analysis of quality of life outcomes in adult and paediatric phase 3 trials (ERA 2025) - P3 | "This analysis demonstrated that ravulizumab treatment was associated with rapid clinically meaningful improvement in QoL measures. Scores improved following ravulizumab treatment and were sustained at or near normal ranges throughout the extension period."

Clinical • HEOR • P3 data • Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • CNS Disorders • Complement-mediated Rare Disorders • Depression • Fatigue • Mood Disorders • Nephrology • Pain • Pediatrics • Psychiatry • Renal Disease

Response to meningococcal vaccination and duration of protection in aHUS patients on Eculizumab (UKKW 2025) - "Introduction Eculizumab and Ravulizumab have revolutionised the treatment of complement mediated aHUS. There was no mortality associated with infection. Patients’ awareness of the signs and symptoms of disease is key to prevent the morbidity and mortality associated with meningococcal infection ."

Clinical • Complement-mediated Rare Disorders • Infectious Disease • Meningococcal Infections • Nephrology

Ravulizumab in atypical hemolytic uremic syndrome: final analysis of efficacy and safety outcomes in two phase 3 trials (UKKW 2025) - No abstract available

Clinical • P3 data • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology

Effectiveness and safety of ravulizumab in generalized Myasthenia Gravis (gMG): Updated analysis from a global registry (CNSF 2025) - No abstract available

Clinical • CNS Disorders • Myasthenia Gravis

Interim efficacy and safety results from the ongoing phase 3 CHAMPION-NMOSD trial of ravulizumab in adults with AQP4-Ab+ NMOSD (CNSF 2025) - No abstract available

Clinical • P3 data • P3 data: top line • CNS Disorders

Study of Ravulizumab in Pediatric Participants With HSCT-TMA (clinicaltrials.gov) - P3 | N=41 | Completed | Sponsor: Alexion Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Bone Marrow Transplantation • Hematological Disorders • Pediatrics • Transplantation

Oral iptacopan monotherapy in paroxysmal nocturnal haemoglobinuria: final 48-week results from the open-label, randomised, phase 3 APPLY-PNH trial in anti-C5-treated patients and the open-label, single-arm, phase 3 APPOINT-PNH trial in patients previously untreated with complement inhibitors. (PubMed, Lancet Haematol) - P3 | "Long-term data indicate durable haemolysis control with iptacopan in paroxysmal nocturnal haemoglobinuria, maintained normal or near-normal haemoglobin, and no new safety concerns. We believe that these data support iptacopan as a potential therapy option, suggesting that we are in a new treatment era for paroxysmal nocturnal haemoglobinuria."

Clinical • Journal • Monotherapy • P3 data • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pain • Paroxysmal Nocturnal Hemoglobinuria

Study of Danicopan as Add-on Treatment to Ravulizumab or Eculizumab in Pediatric Participants With PNH Who Have Clinically Significant Extravascular Hemolysis (clinicaltrials.gov) - P3 | N=6 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Feb 2028 ➔ Jul 2028 | Trial primary completion date: Feb 2027 ➔ Jul 2027

Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Pediatrics • Rare Diseases

A phase 3 study of ravulizumab to protect patients with chronic kidney disease from cardiac surgery-associated acute kidney injury and major adverse kidney events (ARTEMIS). (PubMed, Trials) - P3 | "Complement activation is known to occur during and after cardiac procedures as a result of CPB and ischemia-reperfusion injury, leading to a cycle of cell damage and death. Therefore, it is hypothesized that preoperative administration of ravulizumab will provide immediate and complete complement inhibition, which will be sustained throughout the surgical period, preventing the uncontrolled complement activation associated with the development of CSA-AKI, thus minimizing poor outcomes for patients."

Adverse events • Clinical • Journal • P3 data • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • Reperfusion Injury

FEMALE GENDER IS PROBABLY ASSOCIATED WITH WORSE HEMATOLOGIC RESPONSE TO C5 INHIBITORS IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (EHA 2025) - "This study included 96 patients with PNH who received either an eculizumab biosimilar (Elizaria, n=83) or ravulizumab (Ultomiris, n=13). Female gender is likely associated with a worse hematologic response to C5 inhibitors, potentially due to a higher incidence of extravascular hemolysis. This observation may be speculatively explained by differences in immune system activity between males and females. A history of AA was also identified as a predictor of suboptimal response."

Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

A Cost Minimization and Budget Impact Analysis of an Eculizumab Biosimilar, ABP 959, From the Spanish Healthcare Perspective (ISPOR 2025) - "OBJECTIVES: To estimate the economic consequences of adopting ABP 959, an eculizumab biosimilar, for treating paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). The CMA and BIA both demonstrated substantial estimated cost savings with ABP 959 compared with originator eculizumab and ravulizumab. The savings in drug acquisition costs offset the higher administration costs from more frequent administrations of ABP 959 compared with ravulizumab. These results support the rapid adoption of ABP 959 in treating PNH and aHUS."

HEOR • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

The Role of Complement in the Pathogenesis and Treatment of Myasthenia Gravis. (PubMed, Cells) - "This has led to the development of the first C5 inhibitors approved for myasthenia gravis with AchR antibodies: eculizumab, ravulizumab, and zilucoplan. Other clinical trials are currently in progress, investigating the potential therapeutic role of other targets, including the Factor B inhibition or hepatic synthesis of the C5 protein. Other proposed potential targets that have not yet been clinically tested are also discussed in this review article."

Journal • Review • CNS Disorders • Immunology • Myasthenia Gravis

How Atypical! Relapse of Atypical HUS Presented With Altered Mental Status (ATS 2025) - "A 35-year-old woman with a known history of atypical HUS on Ravulizumab complicated by chronic kidney disease, prior strokes, and uncontrolled hypertension, presented to an outside hospital with altered mental status...Obstructive hydrocephalus is a rare extrarenal manifestation with severe consequences. The heightened awareness of the intensivist can lead to early recognition, and treatment, ultimately improving patient outcomes."

Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Cerebral Hemorrhage • Chronic Kidney Disease • CNS Disorders • Epilepsy • Hypertension • Infectious Disease • Ischemic stroke • Nephrology • Pain • Renal Disease • Thrombocytopenia • Vascular Neurology • Ventriculomegaly