PiaSky (crovalimab-akkz) / Roche - LARVOL DELTA

Short-course anti-CD154 induction followed by tacrolimus maintenance sustains pig-to-cynomolgus kidney xenograft function (TTS 2026) - "Background immunosuppression included rituximab, anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, methylprednisolone, tocilizumab, etanercept, and crovalimab. In three of four recipients, xenograft function persisted after anti-CD154 discontinuation, suggesting that CD154 blockade may durably modulate early allo/xeno-immune priming beyond active dosing. These findings support further investigation of a CD154-based induction-to-tacrolimus maintenance strategy in non-thymokidney xenotransplantation and warrant controlled studies to define optimal duration, mechanisms, reproducibility, safety, and translational applicability in this setting."

Clinical • Nephrology • Transplant Rejection • CD40 • CD40LG • CD55 • ENTPD1

COMPOSER: Study to Assess Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Healthy Volunteers and Participants With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P1/2 | N=59 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

First-in-human • Trial completion • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Indirect treatment comparisons find enhanced effectiveness of pegcetacoplan versus crovalimab in both complement inhibitor-naïve and -experienced patients with paroxysmal nocturnal hemoglobinuria. (PubMed, J Comp Eff Res) - P3 | "Materials & In the C5i-naive, an unanchored matching-adjusted indirect comparison (MAIC) was conducted with patient-level data for pegcetacoplan-versus-best-supportive-care from PRINCE (NCT0408560) and published data for crovalimab-versus-eculizumab from COMMODORE 2 (NCT04434092)/COMMODORE 3 (NCT04654468). In the C5i-experienced, all outcomes significantly (p < 0.05) favored pegcetacoplan. Pegcetacoplan provides high clinical advantages across the full PNH treatment pathway."

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

COMMODORE 2: A Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors (clinicaltrials.gov) - P3 | N=210 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2027 ➔ Apr 2027

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

COMMODORE 1: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors (clinicaltrials.gov) - P3 | N=190 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2027 ➔ Apr 2027 | Trial primary completion date: Sep 2027 ➔ Apr 2027

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

Mapping of C5-Blocking Monoclonal Antibodies Reveals New C5 Inhibitory Epitopes and Novel Modes of C5 Inhibition. (PubMed, Immunology) - "To explore alternative modes of inhibition, novel C5-blocking mAbs were generated and compared to therapeutic mAbs eculizumab and crovalimab. Although all efficiently blocked haemolysis, epitope 3 and 4 binders permitted C5a release. We reveal (at least) four blocking epitopes on C5 and (at least) two distinct mechanisms of inhibition."

Journal • Hematological Disorders

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

EFFICACY AND SAFETY OF SWITCHING TO ORAL HSK39297 MONOTHERAPY IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS WITH PERSISTENT ANEMIA DESPITE ANTI-C5 THERAPY: A PHASE 3 STUDY (HSK39297-302) (EHA 2026) - P3 | "Thirty-six adult PNH patients (hemoglobin [Hb] < 100 g/L) who had received stable anti-C5 therapy (eculizumab/crovalimab) for at least 6 months were switched to oral HSK39297 200 mg once daily for 24 weeks. Summary/Conclusion Switching to oral HSK39297 monotherapy resulted in significant and sustained hemoglobin improvement, near-complete elimination of transfusion need, effective control of hemolysis (including resolution of C3-mediated extravascular hemolysis), and reduced fatigue in PNH patients with persistent anemia on anti-C5 therapy, with a favorable safety profile. HSK39297 represents a promising once- daily oral treatment option for this patient population."

Clinical • Monotherapy • P3 data • Anemia • Complement-mediated Rare Disorders • Dyslipidemia • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Donor-Derived Cell-Free DNA (dd-cfDNA) as an Early Noninvasive Biomarker of Graft Injury in Pig-to-Monkey Islet Xenotransplantation (ATC 2026) - "Cohort 1 received anti-thymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and anti-inflammatory agents (i.e., anakinra, adalimumab, and tocilizumab), whereas Cohort 2 received the same regimen plus rituximab and crovalimab. Our study revealed that dd-cfDNA levels correlate with graft damage and C5a in QKO porcine islet xenografts, which corroborates dd-cfDNA utility as an early biomarker for predicting instant blood mediated inflammatory reaction (IBMIR). Those findings indicate that dd-cfDNA may be able to detect early islet xenograft damage."

Biomarker • cfDNA • Non-invasive • Preclinical • Transplantation • CD68

STATISTICAL ANALYSIS OF EVH IN PNH PATIENTS TREATED WITH C5 INHIBITORS: A REAL-WORLD STUDY (EHA 2026) - "Patients received crovalimab (n=27), eculizumab (n=16), or ravulizumab (n=2)...Following the onset of EVH, management strategies varied: 4 patients (57.1%) continued the current treatment regimen without specific intervention; 1 patient (14.3%) received blood transfusion; 1 patient (14.3%) had corticosteroids added to the regimen; and 1 patient (14.3%) was switched to a factor B inhibitor (iptacopan)...Data presented as median (IQR) or mean ± SD as applicable. PNH: Paroxysmal Nocturnal Hemoglobinuria; WBC: White Blood Cell count; RBC: Red Blood Cell count; HB: Hemoglobin; PLT: Platelet count; RET: Reticulocyte percentage; LDH: Lactate Dehydrogenase; IBIL: Indirect Bilirubin; Cr: Creatinine."

Clinical • Real-world • Real-world evidence • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

REAL-WORLD EXPERIENCE WITH IPTACOPAN IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: EFFICACY IN TREATMENT-NAÏVE AND SWITCH PATIENTS (EHA 2026) - "Aims To evaluate the real-world efficacy and safety of iptacopan in: Patients with PNH switching from C5 inhibitors (eculizumab, ravulizumab, crovalimab) Treatment-naïve patients receiving iptacopan as first-line therapy Methods Study design: Retrospective, single-center analysis Setting: Huashan Hospital, Fudan University, Shanghai, China Patients: 16 patients with PNH treated with iptacopan Data collected: Demographics, baseline HGB, clone size, prior C5i therapy, switch reasons, response to iptacopan, safety . Supports iptacopan as an effective oral option for PNH in real-world settings. Patient treatment timeline"

Clinical • Real-world • Real-world evidence • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • CFB

3-YEAR EFFICACY AND SAFETY OF CROVALIMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) WHO SWITCHED FROM RAVULIZUMAB: LONG-TERM DATA FROM THE PHASE III COMMODORE 1 TRIAL (EHA 2026) - P3 | "In COMMODORE 2 (NCT04434092), crova demonstrated non-inferior efficacy vs eculizumab (ecu) in C5i- naive pts (Röth 2024). These exploratory data warrant cautious interpretation due to the small sample size and disease variability. BTH, breakthrough hemolysis; Hb, hemoglobin; TA, transfusion avoidance."

Clinical • P3 data • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Hepatology • Infectious Disease • Meningococcal Infections • Musculoskeletal Pain • Novel Coronavirus Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • PIAS4

REAL-WORLD PATIENT-REPORTED TREATMENT BURDEN FROM 106 PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: RESULTS FROM THE VOICE CROSS-SECTIONAL QUANTITATIVE SURVEY (EHA 2026) - "Current treatment for most pts was complement inhibitor therapy (86%), most commonly ravulizumab (59%), crovalimab (11%), or iptacopan (10%); 12 pts received danicopan in combination with ravulizumab (n=11) or crovalimab (n=1). Figure. PNH treatment-related burden (N=106)"

Clinical • Real-world • Real-world evidence • Complement-mediated Rare Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

REAL-WORLD EFFECTIVENESS OF PEGCETACOPLAN IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) AFTER SWITCH FROM C5 INHIBITORS AMONG CEE COUNTRIES (EHA 2026) - "The indication for switching from C5i to PEG was EVH leading to anaemia in all cases (eculizumab n=27, ravulizumab n=9, crovalimab n=2). During almost 20 months of treatment, the median LDH remained below 1.5x ULN, indicating good control of intravascular hemolysis. BTH events on PEG can be severe, but timely interventions in accordance with the guidelines resolve them effectively."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Bone Marrow Transplantation • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

3-YEAR EFFICACY AND SAFETY OF CROVALIMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) NAIVE TO COMPLEMENT INHIBITORS: LONG-TERM DATA FROM THE PHASE III COMMODORE 2 TRIAL (EHA 2026) - P3 | "These findings further confirm the long-term favorable benefit–risk profile of crova in pts with PNH. BTH, breakthrough hemolysis; crova, crovalimab; ecu, eculizumab; Hb, hemoglobin; TA, transfusion avoidance."

Clinical • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Musculoskeletal Pain • Novel Coronavirus Disease • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases • PIAS4

3-YEAR EFFICACY AND SAFETY OF CROVALIMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) WHO SWITCHED FROM ECULIZUMAB: LONG-TERM DATA FROM THE PHASE III COMMODORE 1 TRIAL (EHA 2026) - P3 | "These results confirm the favorable long-term benefit–risk profile of crova. BTH, breakthrough hemolysis; crova, crovalimab; ecu, eculizumab; Hb, hemoglobin; TA, transfusion avoidance."

Clinical • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Musculoskeletal Pain • Novel Coronavirus Disease • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases • PIAS4

PLATELET PNH CLONE ASSESSMENT BY FLOW CYTOMETRY ISFEASIBLE AND PROVIDES A RELIABLE ESTIMATE OF CLONE SIZE AND PLATELET ACTIVATION IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (EHA 2026) - "The cohort comprised 61.1% classic PNH and 38.9% PNH with bone marrow failure; 77.8% were receiving complement inhibitors (eculizumab or crovalimab). Elevated baseline CD62P expression in treated patients suggests persistent platelet activation despite anti-C5 therapy, supporting further investigation of platelet dysfunction and residual thrombotic risk. Future studies should expand platelet markers, activation analysis, and include treatment-naïve patients."

Clinical • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Neutropenia • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • CD55 • CD58 • CD59 • ITGB3 • SELP

DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF CROVALIMAB FOR THE TREATMENT OF ACUTE VASO-OCCLUSIVE EPISODES IN SICKLE CELL DISEASE: RESULTS OF THE PHASE 1B CROSSWALK-A TRIAL (EHA 2026) - P1 | "§ Defined as the first of: sustained ≥2-point pain score reduction with transition to oral analgesics, readiness for discharge, or hospital discharge. AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; crova, crovalimab; hrs, hours; ITT, intention to treat; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; pbo, placebo; pts, patients; SAE, serious adverse event; VOE, vaso-occlusive episode."

Clinical • P1 data • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Infectious Disease • Meningococcal Infections • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Sickle Cell Disease

DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF CROVALIMAB AS ADJUNCT TREATMENT FOR THE PREVENTION OF VASO-OCCLUSIVE EPISODES IN SICKLE CELL DISEASE: RESULTS FROM THE PHASE 2A CROSSWALK-C TRIAL (EHA 2026) - P2 | "No statistical testing was performed for secondary endpoints. AR, annualized rate; CI, confidence interval; crova, crovalimab; EEP, exploratory efficacy population (patients who met inclusion/exclusion criteria relevant to the primary endpoint and received ≥80% expected crova exposure); ITT, intention-to-treat; MF, medical facility; pbo, placebo; SD, standard deviation; VOE, vaso-occlusive episode."

Clinical • P2a data • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Meningococcal Infections • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Sickle Cell Disease

Efficacy and Safety of Treatments for Paroxysmal Nocturnal Hemoglobinuria: A Systematic Literature Review. (PubMed, J Clin Med) - "The first treatments approved were complement 5 inhibitors (C5is), eculizumab and ravulizumab. Recently approved treatments include pegcetacoplan, iptacopan, danicopan (as an add-on to a C5i), and crovalimab... This SLR is the first to provide an overview of clinical trials assessing the efficacy and safety of all currently approved PNH treatments, which could help inform clinical decisions. Although some head-to-head trials are available, direct comparative evidence remains limited for several comparators, necessitating an indirect treatment comparison (ITC) to assess the efficacy and safety across the treatment landscape."

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

Efficacy, safety and pharmacokinetics/pharmacodynamics of crovalimab for paediatric atypical haemolytic uraemic syndrome: Phase III COMMUTE-p trial (ERA 2026) - P3 | "C5 inhibitors (C5is), such as eculizumab (ecu) and ravulizumab (ravu), are approved for paediatric pts with aHUS, but require regular intravenous (IV) infusions and can be burdensome. Overall, the benefit–risk profile is positive and supports the use of crova for the treatment of paediatric pts with aHUS, with the potential to reduce treatment burden. Image"

Clinical • Late-breaking abstract • P3 data • PK/PD data • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Pediatrics • Renal Disease

Exploring individualized crovalimab dosing in PNH through in silico modelling: Potential for improved convenience and cost efficiency. (PubMed, Br J Clin Pharmacol) - "Individualized dosing of crovalimab may reduce exposure variability and enable less frequent dosing, supporting the feasibility of more flexible cost-effective and patient-tailored treatment regimens."

Journal • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

Efficacy, safety and pharmacokinetics/pharmacodynamics of crovalimab for atypical haemolytic uraemic syndrome (aHUS): Phase III COMMUTE-a trial (ERA 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • PK/PD data • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders

Complement C5 inhibitor crovalimab for the treatment of paroxysmal nocturnal hemoglobinuria. (PubMed, Expert Rev Clin Pharmacol) - "Some PNH patients carrying the C5 mutation (Arg885) show poor response to eculizumab and ravulizumab. Additionally, crovalimab showed a favorable response in PNH patients carrying C5 variants, and the response in adolescents aged ≥ 13 years was similar to that in adults. Common adverse events associated with crovalimab include infusion-related reactions, respiratory tract infections, and Type III hypersensitivity reactions."

Journal • Review • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Respiratory Diseases • Thrombosis • PIAS4

PSYCHOMETRIC VALIDATION OF THE QLQ-AA/PNH-54 BASED ON A POOLED DATASET OF A CLINICAL TRIAL AND TWO REAL-WORLD STUDIES OF CROVALIMAB IN PARTICIPANTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (ISPOR 2026) - "QLQ-AA/PNH-54 demonstrated mostly strong psychometric properties based on a pooled dataset of 3 crovalimab studies of participants with PNH."

Clinical • Real-world • Real-world evidence • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases