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

Pharmacological Therapies in Paroxysmal Nocturnal Haemoglobinuria: Focus on Complement Inhibition. (PubMed, Drugs) - "This has been largely supplanted by a longer-acting antibody, ravulizumab, targeting the same binding site on C5...Other terminal inhibitors available include eculizumab biosimilars, crovalimab, pozelimab and cemdisiran (combination)...Currently available proximal inhibitors (and their targets) are pegcetacoplan (C3), danicopan (Factor D) and iptacopan (Factor B). While effective, as with all other complement inhibitors, there is a risk of breakthrough IVH with their use and approaches to manage this complication are being developed."

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

Managing transient immune complex reactions in patients with paroxysmal nocturnal hemoglobinuria: clinical observations from the COMMODORE 1 and 2 studies. (PubMed, Ther Adv Hematol) - P3 | "The COMMODORE 1 nonrandomized, descriptive cohort included patients who previously received ravulizumab or approved or higher-than-approved doses of eculizumab. These results further confirm that crovalimab is well tolerated in patients with PNH. NCT04432584; NCT04434092."

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

Post marketing real-world experience of ravulizumab in NMOSD. (PubMed, Mult Scler Relat Disord) - "Early post-marketing real-world experience with ravulizumab in the UAE is consistent with pivotal trial results and aligns with the safety and efficacy profiles reported for other complement-targeted therapies; however, findings are limited by the small sample size and short follow-up."

Journal • P4 data • Real-world evidence • CNS Disorders • Infectious Disease • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

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

Biomarker • Enrollment open • Real-world evidence • CNS Disorders • Myasthenia Gravis

Alexion, AstraZeneca Rare Disease, will present four abstracts, including one oral presentation, from its leading rare neurology portfolio at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Annual Congress in Barcelona, Spain, 24 to 26 September 2025. (AstraZeneca Press Release) - "...a virtual poster presentation will share findings from the ongoing AMAZE study, a 78-week observational trial to evaluate the biological effects of Ultomiris, on clinical, serological and radiological measures of disease, and better understand the impact of social determinants of health on access to care and treatment outcomes for living with AQP4-Ab+ NMOSD."

Observational data • Neuromyelitis Optica Spectrum Disorder

A separate poster presentation will share interim analysis results from a real-world study from Japan evaluating Ultomiris in patients with AQP4-Ab+ NMOSD who had a suboptimal response to satralizumab. (AstraZeneca Press Release) - "Among 11 patients receiving Ultomiris for at least six months (10.9±1.4 months on average), 10 remained relapse-free. In addition, use of concomitant immunosuppressive drugs was reduced in all patients. The switch to Ultomiris also showed positive changes in inflammatory biomarkers, as measured by changes in CD19+CD27-IgD- double negative B cells (%DNB) and unswitched memory B cells (%USM) at two months follow-up after treatment initiation."

Real-world • Neuromyelitis Optica Spectrum Disorder

A virtual poster presentation will feature real-world clinical findings from the global NMO SPOTLIGHT Registry, showing that Ultomiris and Soliris led to a reduction in relapses for people with AQP4-Ab+ NMOSD. (AstraZeneca Press Release) - "Among 56 adults, the annualised relapse rate (ARR) fell from 0.50 [95% CI: 0.33-0.72] during the year prior to starting treatment with Ultomiris or Soliris to 0.02 [95% CI: 0.00-0.05] while on treatment, with no one experiencing more than one relapse. Among patients who switched from rituximab (n=15), no relapses were reported while treated with Ultomiris or Soliris, compared to an ARR of 0.47 [95% CI: 0.19-0.96] in the year prior to switching."

Real-world • Neuromyelitis Optica Spectrum Disorder

An oral presentation of the final safety and efficacy results from the long-term extension (LTE) of the global CHAMPION-NMOSD Phase III trial will demonstrate zero adjudicated on-trial relapses (OTR) in adults with AQP4-Ab+ NMOSD treated with Ultomiris through the median follow-up of 170.3 weeks (relapse risk reduction: 98.9%, hazard ratio (95% CI), 91.8-100; P < 0.0001). (AstraZeneca Press Release) - "Additionally, most patients treated with Ultomiris were clinically stable (81%) or improved (13.8%), as measured by the Hauser Ambulation Index (HAI) score, and had no clinically important worsening (91.4%) of disability measured with the Expanded Disability Status Scale (EDSS)."

P3 data • Neuromyelitis Optica Spectrum Disorder

Treatment of Patients with Donor-Specific Anti-HLA Antibodies (ICBMT 2025) - "Rituximab induces B-cell depletion by targeting CD20, reducing DSA production. Proteasome inhibitors like bortezomib or carfilzomib target plasma cells, inducing apoptosis by disrupting the ubiquitin-proteasome pathway...Post-transplant cyclophosphamide (PTCy) has demonstrated particular efficacy in the context of haploidentical HSCT, owing to its capacity to selectively eliminate alloreactive T cells...Complement inhibition strategies, utilizing agents such as eculizumab (a monoclonal antibody targeting C5) or next-generation complement inhibitors like ravulizumab, aim to abrogate complement-mediated HSC destruction. Imlifidase, a bacterial-derived IgG-degrading enzyme (IdeS), is currently under investigation for its capacity to rapidly and profoundly reduce DSA levels by cleaving IgG antibodies...Continued collaboration among clinicians, researchers, and immunologists is essential to advance HSCT. By leveraging our expanding knowledge of DSA biology, refining risk..."

Clinical • Bone Marrow Transplantation • Hematological Disorders • Immunology • Targeted Protein Degradation

Eculizumab and ravulizumab clinical trial and real-world pharmacovigilance of meningococcal infections across indications. (PubMed, PLoS One) - "Meningococcal infection and mortality reporting rates have remained stable despite increasing cumulative eculizumab and ravulizumab exposure over time across indications, including rare neurological indications. Infection awareness, existing risk mitigation strategies, and availability of vaccines have effectively reduced the risk of meningococcal infections in C5IT-treated patients, underlining the importance of adhering to those measures."

Adverse events • Journal • Real-world evidence • CNS Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections

Real-world experience with ravulizumab in myasthenia gravis: Efficacy, challenges, and need for combination therapy (EAN 2025) - No abstract available

Clinical • Combination therapy • Real-world • Real-world evidence • CNS Disorders • Myasthenia Gravis

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 (ICBMT 2025) - P3 | " Fifty-two pts were enrolled (mean age: 46.0 years; female: 38.5%; mean time since diagnosis: 10.8 years [SD 7.5]); 88.5% switched from ravulizumab and 11.5% from eculizumab. 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 • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases

Study of Ultomiris® (Ravulizumab) Safety in Pregnancy (clinicaltrials.gov) - P=N/A | N=75 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Oct 2034 ➔ Jul 2034 | Trial primary completion date: Oct 2034 ➔ Jul 2034

Trial completion date • Trial primary completion date • Atypical Hemolytic Uremic Syndrome • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

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

Successful Control of Chemotherapy-Induced Breakthrough Hemolysis With Ravulizumab in a Patient With Paroxysmal Nocturnal Hemoglobinuria During Carboplatin-Pemetrexed Treatment for Lung Adenocarcinoma. (PubMed, Cureus) - "After discontinuing first‑line osimertinib due to diarrhea, second‑line carboplatin-pemetrexed (chemotherapy regimen consisting of carboplatin and pemetrexed) induced severe BTH, evidenced by lactate dehydrogenase rising to 2,462 U/L and hemoglobin (Hb) dropping to 4.6 g/dL. Personalized scheduling of ravulizumab enabled uninterrupted cytotoxic chemotherapy by effectively managing BTH, suggesting that sustained complement C5 inhibition may confer oncologic benefits. Prospective studies are warranted to evaluate the broader impact of complement blockade in patients with PNH and malignancy."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Solid Tumor • Thrombosis • EGFR

ARTEMIS: Ravulizumab to Protect Patients With CKD From CSA-AKI and MAKE (clinicaltrials.gov) - P3 | N=736 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Heart Failure • Nephrology • Renal Disease • CST3

Paroxysmal nocturnal hemoglobinuria with large clones in non-hypoplastic myelodysplastic syndrome- report of two cases. (PubMed, Acta Haematol) - "The patient showed initial benefit from ravulizumab and, he was later switched to pegcetacoplan, which led to effective disease control. Regarding PNH treatment in such patients, we found that they are underrepresented in studies investigating complement inhibitor. However, standard doses recommended for PNH appear effective and safe regardless of the underlying disease."

Journal • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Hypertension • Myelodysplastic Syndrome • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases • SF3B1

Transplacental transfer of ravulizumab in a pregnant woman with neuromyelitis optica: a case report. (PubMed, BMJ Neurol Open) - "Case presentation We report a case of a 41-year-old woman with aquaporin-4 (AQP4) IgG positive NMOSD who was switched from rituximab to ravulizumab during pregnancy. These findings suggest that ravulizumab may be a viable treatment option for NMOSD during pregnancy when traditional agents are contraindicated or ineffective. However, further studies and longitudinal monitoring of exposed infants are essential to establish safety and clinical guidelines."

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

Clinical characteristics and management of paroxysmal nocturnal hemoglobinuria in the Middle East: a narrative review. (PubMed, Clin Exp Med) - "Few publications reported on treatment with C5 inhibitors, although available data indicate that eculizumab generally improves patients' clinical condition. Uptake and clinical use of ravulizumab in the Middle East remains undocumented. Subject to limitations of the available data, the management approach to PNH in the Middle East appears to be generally consistent with that reported in other regions. However, additional data are required to gain greater insight into the status of PNH and its management in Middle Eastern populations."

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

New treatment strategies for paroxysmal nocturnal hemoglobinuria: drug selection in the era of novel complement inhibitors (PubMed, Rinsho Ketsueki) - "Eculizumab (Ecu), a C5 inhibitor, blocks intravascular hemolysis (IVH) and improves prognosis. Ravulizumab and crovalimab have longer half-lives, and reduce treatment burden...Pegcetacoplan (C3 inhibitor) improves anemia better than Ecu. Danicopan (factor D inhibitor) and ipracopan (factor B inhibitor) also improve anemia and fatigue...In addition, long-term real-world infection data remain necessary. While IVH control has improved PNH prognosis, future therapies should focus on patients with persistent anemia or insufficient improvement in quality of life, and should aim to enhance hemoglobin levels and overall well-being while managing BTH for optimal care."

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

Successful treatment of severe IVIG-induced immune hemolytic anemia with ravulizumab in a patient with systemic lupus erythematosus: a therapeutic challenge. (PubMed, Rheumatology (Oxford)) - No abstract available

Journal • Anemia • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

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

Clinical and Serological Profile of Myasthenia Gravis in the O'Higgins Region of Chile: A Regional Study. (PubMed, Cureus) - "Most patients received cholinesterase inhibitors; corticosteroids were used in 74.6% of cases, and one-third were treated with conventional immunosuppressants. A smaller group received biological therapies such as rituximab or other newer agents, ravulizumab. Despite the range of available treatments, approximately 20% of patients exhibited a refractory disease course. MG is a disease with a multifaceted impact on patients' personal, social, and occupational lives. The findings of this study may support the development of targeted health policies aimed at improving comprehensive care for MG patients in Chile."

Journal • Cardiovascular • CNS Disorders • Endocrine Disorders • Hypertension • Immunology • Mood Disorders • Myasthenia Gravis • Psychiatry

SARS-CoV-2 infection could act as a trigger for TMA in patients with an underlying complement defect. Case report (ECP 2025) - "Early treatment with ravulizumab was initiated... Hypotheses have been developed that propose that "two triggers" are required for the development of aHUS, such as the combination of genetic background and a triggering factor. In our case, the patient meets both criteria since she presents a genetic factor, such as the presence of a genetic mutation that inactivates the gene encoding CFH, preventing the expression of FH proteins, and risk polymorphisms for aHUS in the MCP gene; and a triggering factor, such as COVID infection. There is data in the literature that supports the theory that SARS-CoV-2 infection could act as a trigger for TMA in patients with an underlying complement defect, although the mechanism that causes it is unknown."

Case report • Clinical • Acute Kidney Injury • Anemia • Atypical Hemolytic Uremic Syndrome • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Thrombocytopenia • HP

Ravulizumab stabilizes life-threating intravascular hemolysis following delayed hemolytic transfusion reaction due to alloantibodies anti-e and anti-Jka: the first successful administration. (PubMed, Ann Hematol) - "Within three weeks there was full hematologic and biochemical recovery. This case demonstrates the therapeutic potential of ravulizumab in the management of severe complement-mediated hemolysis due to DHTR, and highlights the need for further research on complement inhibitors in similar conditions."

Journal • Hematological Disorders • AR