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

First and Second Genetically Modified Pig Kidney Xenotransplants in Living Human Recipients: Immunological and Physiological Insights (WTC 2025) - "Induction immunosuppression included rituximab, rabbit ATG, steroids, and complement inhibition (ravulizumab in Patient 1, pegcetacoplan in Patient 2). Maintenance therapy consisted of tegoprubart (anti-CD154mAb), tacrolimus, mycophenolate, and prednisone.* Clinical Course: Patient 1: Achieved immediate urine production, with serum creatinine decreasing from 8 to 2 mg/dL within one week... These first-in-human xenotransplants showed immediate graft function, stable metabolism, and no early antibody-mediated rejection, demonstrating feasibility of kidney xenotransplantation. Differences in Ca-Phos metabolism were likely related to absence of PTH on the first patient. Xenotransplantation offers a promising solution for patients facing prolonged wait times."

Anemia • Antibody-mediated Rejection • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Endocrine Disorders • Heart Failure • Hematological Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Pain • Peripheral Arterial Disease • Transplant Rejection • Transplantation • CD40LG

Discontinuation of Complement Inhibitors After the Resolution of Thrombotic Microangiopathy Post-Kidney Transplant (WTC 2025) - "Various strategies may be implemented to mitigate the progression of allograft dysfunction, such as using complement inhibitors (CI), discontinuation of CNIs, or conversion to belatacept...Standard maintenance immunosuppression included tacrolimus and mycophenolate with/without prednisone maintenance.* Thirty-one of 2273 (1.4%) KT recipients who received eculizumab were included in the analysis...Six patients (19%) were converted to ravulizumab... Most KT recipients receiving a CI for early complications of TMA can be successfully discontinued from therapy, especially in those individuals without any known genetic variants."

Antibody-mediated Rejection • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology • Transplantation

Successful Transplant Outcome in a Patient with Renal aHUS Manifesting as Hypertension (WTC 2025) - "Post transplant, he had no complications and was maintained on mycophenolate mofetil, tacrolimus, prednisone and eculizumab. He continued to have stable renal function and eventually was switched to Ultomiris... Complement dysregulation results from mutations in the alternative and common complement pathways leading to renal limited endovascular damage. Rarely, systemic hematologic changes such as TMA of TTP are seen. The diagnosis is made by a high index of suspicion and genetic testing."

Clinical • Anemia • Atherosclerosis • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hypertension • Nephrology • Thrombocytopenic Purpura • Transplantation • CFH

Early Myasthenia Gravis Activities of Daily Living (MG-ADL) Response to Ravulizumab in Acetylcholine Receptor-Positive Generalized Myasthenia Gravis Refractory: A Case Report From Latin America. (PubMed, Cureus) - "This case report details the first use of ravulizumab in Chile for a patient with acetylcholine receptor (AChR)-positive myasthenia gravis (MG) who did not respond to rituximab (RTX). Ravulizumab, a monoclonal antibody that inhibits complement component C5, was approved for MG in 2022 and is being assessed for efficacy in neurological disorders. This report highlights its potential as a therapy for MG in the absence of robust local evidence, offering a novel therapeutic option for managing this debilitating condition."

Journal • CNS Disorders • Fatigue • Myasthenia Gravis

Early Ravulizumab Treatment Of Anti- AChR Antibody-Positive Generalized Myasthenia Gravis (clinicaltrials.gov) - P=N/A | N=40 | Not yet recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Initiation date: Jun 2025 ➔ Sep 2025

Biomarker • Real-world evidence • Trial initiation date • CNS Disorders • Myasthenia Gravis

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

Safety of Drugs in Breastfeeding Women With CKD. (PubMed, Kidney Int Rep) - "Among renin-angiotensin system inhibitors, enalapril and captopril are safe for breastfeeding. Based on limited evidence, quinapril, benazepril, candesartan, and valsartan are likely acceptable for use during breastfeeding. We found no compelling human data regarding the safety of other renin-angiotensin system inhibitors or sodium-glucose cotransporter type 2 (SGLT2) inhibitors, finerenone, sparsentan, or glucagon-like peptide-1 receptor agonists (GLP1RAs) in lactation. Immunosuppressive agents, including azathioprine, cyclosporine, tacrolimus, budesonide, rituximab, and eculizumab are acceptable for use during breastfeeding. Belimumab is most likely safe; however, data are limited...No studies were found on the safety of breastfeeding while on the newer complement inhibitors, including avacopan, ravulizumab, iptacopan, and pegcetacoplan...Human lactation data on the safety of most drugs used in the treatment of CKD are limited, making evidence-based recommendations..."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Crovalimab: A Novel Approach in the Management of Paroxysmal Nocturnal Hemoglobinuria. (PubMed, Health Sci Rep) - "Currently available terminal complement inhibitors, such as Eculizumab and Ravulizumab, pose several challenges, including the need for frequent intravenous infusions and the potential for resistance due to C5 polymorphisms. Crovalimab represents a significant advancement in the management of PNH, with the potential to reduce treatment burden while maintaining efficacy. However, further research is required to evaluate its long-term safety and effectiveness across diverse populations."

Journal • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Clinical insights on "Effectiveness and safety of ravulizumab for Japanese patients with atypical hemolytic uremic syndrome (aHUS) switched from eculizumab". (PubMed, Clin Exp Nephrol) - No abstract available

Journal • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology

Perioperative Considerations of a Myasthenia Gravis Patient with Epidural Metastasis and Prior Pneumonectomy: A Case Report (ASA 2025) - "She also receives bimonthly Ravulizumab infusions. Due to her disease severity and medical history, pyridostigmine was continued intravenously intraoperatively. This discussion will address the pathophysiology of myasthenia gravis, drug interactions with pyridostigmine, and predictive factors of postoperative respiratory failure."

Case report • Clinical • CNS Disorders • Gastrointestinal Disorder • Myasthenia Gravis • Respiratory Diseases • Solid Tumor • Thymoma • Thymus Cancer

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

Long-term effectiveness and safety of ravulizumab in paroxysmal nocturnal hemoglobinuria: a plain language summary. (PubMed, J Comp Eff Res) - "In studies 301 and 302, ravulizumab had a lower risk of BTH compared to eculizumab. This study shows that ravulizumab remains safe and effective for longterm PNH treatment."

Journal • Review • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Case Report: Failure of eculizumab to block complement to prevent relapse of anti-phospholipid syndrome in kidney transplant recipient. (PubMed, Front Nephrol) - "This suggests that inadequate complement blockade leads to a relapse of APS in the renal allograft with cortical necrosis and dysfunction. Our case highlights the importance of monitoring complement activity and adjusting the dose of eculizumab or ravulizumab."

Journal • Acute Kidney Injury • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Nephrology • Thrombosis • Transplantation

Pharmacological characteristics and clinical study results of danicopan (Voydeya® tablets) (PubMed, Nihon Yakurigaku Zasshi) - P3 | "Complement C5 inhibitors (C5i; eculizumab and ravulizumab) are the current standard of care of PNH treatment, and control intravascular hemolysis (IVH) by inhibiting terminal complement pathway activation. No new safety concerns were observed. Danicopan makes it possible to control EVH while controlling IVH with C5i."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • CD55 • CD59

Navigating the paroxysmal nocturnal hemoglobinuria (PNH) landscape. (PubMed, Clin Adv Hematol Oncol) - "C5 inhibitors approved by the US Food and Drug Administration (FDA) include eculizumab (administered intravenously every 2 weeks), ravulizumab (administered intravenously every 8 weeks), and, most recently, crovalimab (administered subcutaneously every 4 weeks)...The C3 inhibitor pegcetacoplan (administered subcutaneously twice weekly) and the factor B inhibitor iptacopan (administered orally twice daily), both used as single agents, have demonstrated effective control of hemolysis with increased hemoglobin and transfusion avoidance in both C5 inhibitor-naive and C5 inhibitor-experienced patients with clinically significant extravascular hemolysis. The factor D inhibitor danicopan (administered orally 3 times a day) is used as an add-on to ravulizumab or eculizumab and offers a combination approach by targeting both terminal complement and the alternative pathway. Breakthrough hemolysis in the event of a strong complement trigger is possible on any complement inhibitor,..."

Journal • Review • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Clinical Study to Evaluate the Effects of the Complement C5 Inhibitor Ravulizumab on Serum Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) Levels in Patients With Aquaporin-4-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) (clinicaltrials.gov) - P=N/A | N=40 | Not yet recruiting | Sponsor: National and Kapodistrian University of Athens | Initiation date: May 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2027 ➔ Sep 2027

Trial initiation date • Trial primary completion date • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Ravulizumab is Effective and Safe for Neuromyelitis Optica Spectrum Disorder Patients in Various Clinical Settings: A Single-Center Case Series with Concomitant Use of Rituximab. (PubMed, Cureus) - "Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by inflammation of the optic nerves and spinal cord, often associated with anti-aquaporin-4 antibodies. Further studies are warranted to evaluate whether the relapse rate in patients who switched to RTX using this method is comparable to that in patients who initiated RTX in combination with conventional steroids. Additionally, research is needed to establish safe switching strategies from RVZ to other biologic agents such as satralizumab or inebilizumab."

Journal • CNS Disorders • Immunology • Infectious Disease • Inflammation • Neuromyelitis Optica Spectrum Disorder • Novel Coronavirus Disease • Optic Neuritis • Pain • Rare Diseases

Ravulizumab-related meningococcal sepsis post rituximab. (PubMed, Pract Neurol) - "However, vaccination in the context of treatment sequencing from other immunosuppressive therapies, in particular rituximab, presents unique challenges. We present a 17-year-old woman with a severe NMOSD relapse despite B-cell depletion, who subsequently developed meningococcal sepsis after treatment with ravulizumab, despite prior vaccination; and we propose strategies to manage risk in this patient population."

Journal • CNS Disorders • Infectious Disease • Meningococcal Infections • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • Septic Shock

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

Interim symptom and treatment data from an app-based study on paroxysmal nocturnal hemoglobinuria (ISTH 2025) - P | "At enrollment, participants report baseline health (medical history, treatment history, and demographic information) and customize their Folia Health app profile by adding symptoms they are experiencing and treatments they are taking (e.g. iptacopan, danicopan, ravulizumab, pegcetacoplan). Tables 1 and 2 outline most common symptoms and PNH treatments selected for tracking. Table or Figure Upload"

Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

OBTAINING INSIGHTS ON PNH MANAGEMENT WITH IPTACOPAN IN EVERYDAY CLINICAL PRACTICE: A RESEARCH COLLABORATION WITH THE IPIG PNH REGISTRY (EHA 2025) - P | "It compares favorably to other complement inhibitors (CI) like eculizumab and ravulizumab. This research collaboration is advancing research and innovation in PNH. Recruiting patients for PNH studies is challenging due to its rarity. The IPIG PNH Registry supports collaborative efforts to gather real-world data on patient outcomes and treatment efficacy."

Clinical • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

APPULSE-PNH: ORAL IPTACOPAN MONOTHERAPY DEMONSTRATES CLINICALLY MEANINGFUL HEMOGLOBIN (HB) INCREASES IN PATIENTS (PTS) WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) AND HB ≥10 G/DL ON ANTI-C5 THERAPY (EHA 2025) - P3 | "Iptacopan, the first oral selective factor B inhibitor, had superior efficacy vs anti-C5 (eculizumab/ravulizumab) in pts with PNH and Hb <10 g/dL on anti-C5 in APPLY-PNH (NCT04558918). APPULSE-PNH met its primary and key secondary objectives. Oral iptacopan monotherapy led to clinically meaningful increases in Hb, Hb normalization in almost all pts, transfusion avoidance in all pts and reductions in ARC. Pts also reported improvements in fatigue and treatment satisfaction."

Clinical • Monotherapy • CNS Disorders • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Pain • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases

EFFICACY OF COMPLEMENT INHIBITORS AND HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A META ANALYSIS AND SYSTEMATIC REVIEW (EHA 2025) - "Among the patients receiving treatment, the transfusion avoidance rate of the Eculizumab group was 84% (95% CI: [78%, 89%]), vs Ravulizumab group was 46% (95% CI: [0%, 98%]),vs Pegetacoplan was 88% (95% CI: [79%, 93%]), and Iptacopan continued to show significant efficacy, with a transfusion avoidance rate of 95% (95% CI: [88%, 100%]). As the first-line treatment option, complement inhibitors has positive effect for PNH, allogeneic HSCT is an effective treatment option for patients with invalid or inaccessible complement inhibitors."

Retrospective data • Review • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Transplantation

NETWORK META-ANALYSIS COMPARING THE EFFICACY OF DIFFERENT COMPLEMENT PATHWAY INHIBITORS FOR THE TREATMENT OF PAROXYSMAL NOCTURNAL HEMATURIA (EHA 2025) - "Aims: We performed a systematic review and network meta-analysis comparing the efficacy of four new complement inhibitors: pegcetacoplan, iptacopan, danicopan, and crovalimab, to aid in the decision-making process regarding the optimal drug choice for the treatment of PNH. Proximal complement inhibitors are more effective than eculizumab/ravulizumab in controlling anemia-related symptoms of PNH. While there is no significant difference between novel proximal complement inhibitors, our results suggest that iptacopan or pegcetacoplan may be the preferred drug. Additional factors such as route and frequency of drug administration should be taken into consideration when selecting the optimal treatment choice for the patients."

Retrospective data • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

A SINGLE INSTITUTION EXPERIENCE OF IPTACOPAN IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (EHA 2025) - "Mean changes from baseline to 3 months included the following: Hgb (11.9±1.35 g/dL to 12.3±1.76 g/dL), reticulocytes (.130±.08 cells/µL to .083±.02 cells/µL), LDH (485±541 IU/L to 457±129 IU/L), PNH erythrocyte clone size + 17.0% and granulocyte clone size +30.9%.As to the CI-switched cases, 25 patients had suboptimal response to ravulizumab (n=16), pegcetacoplan (n=6), and eculizumab (n=3). Iptacopan was associated with significant improvements in hemolysis markers and hemoglobin levels at 3 months. Although longer follow-up is needed to confirm durability and safety, these results suggest that oral factor B inhibition can be an effective and convenient alternative for patients with PNH, particularly for those who are either treatment-naïve or have an inadequate response to existing parenteral therapies."

Clinical • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases