PiaSky (crovalimab-akkz) / Roche - LARVOL DELTA

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

2-YEAR EFFICACY AND SAFETY IN PATIENTS (PTS) WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) WHO SELF-ADMINISTERED CROVALIMAB (CROVA) IN THE PHASE III RANDOMIZED COMMODORE 2 TRIAL (EHA 2025) - P3 | "Results from the COMMODORE 2 (NCT04434092) primary treatment (tx) period demonstrated non-inferior efficacy and comparable safety of crova vs eculizumab (ecu) in C5i-naive pts with PNH. In COMMODORE 2, crova was well tolerated and maintained disease control over a 2-year median follow-up in C5i-naive pts with PNH, regardless of who administered the drug. These results further support the long-term favorable benefit-risk profile of crova and the feasibility of crova self-administration."

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

A SINGLE CENTER REAL-WORLD STUDY ON THE EFFICACY AND RECOVERY OF INFLAMMATORY CYTOKINE LEVELS OF C5 COMPLEMENT INHIBITOR THERAPY IN PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA PATIENTS (EHA 2025) - "We retrospectively analyzed the efficacy and safety of C5 complement inhibitors (Eculizumab or Crovalimab) in 57 patients with PNH in a single center. Our research confirms the good efficacy and tolerability of C5 inhibitors in Chinese PNH patients. We also found that some complements and cytokines maybe predictive indicators for efficacy evaluation."

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

Advancements in Complement Inhibition for PNH and Primary Complement Mediated Thrombotic Microangiopathy. (PubMed, Blood Adv) - "These agents currently include pegcetacoplan, a C3 inhibitor, iptacopan, an oral factor B inhibitor, danicopan, an oral factor D inhibitor, and crovalimab, an anti-C5 monoclonal antibody. In addition, we review current data supporting the use of these novel agents for aHUS, for which only the terminal complement inhibitors eculizumab and ravulizumab are currently approved. Future research is crucial to establish the long-term efficacy and safety profiles of these novel therapies, ensuring the best treatment strategies for patients with PNH and aHUS."

Journal • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

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

Systematic Literature Review and Network Meta-Analysis of Crovalimab Compared With Eculizumab, Ravulizumab and Best Supportive Care in Paroxysmal Nocturnal Hemoglobinuria (ISPOR 2025) - "NMA results indicated a high probability that crovalimab is associated with non-inferior clinical outcomes vs ravulizumab for C5 inhibitor-naive and pre-treated patients. Quality of life measured by FACIT-Fatigue score was numerically better vs ravulizumab and statistically better vs eculizumab."

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

Horizon Scanning for Paroxysmal Nocturnal Hemoglobinuria in Brazil: Insights on Past Trends and Future Prospects (ISPOR 2025) - " We identified 10 treatments for PNH, six of which had FDA approval: eculizumab (2007, intravenous C5 inhibitor), ravulizumab (2018, intravenous C5 inhibitor), pegcetacoplan (2021, subcutaneous C5 inhibitor), iptacopan (2023, oral factor B inhibitor), danicopan (2024, oral factor D inhibitor used with eculizumab or ravulizumab), and crovalimab (2024, intravenous/subcutaneous C5 inhibitor). Recent cooperation between ANVISA and the FDA promises to accelerate drug approvals in Brazil. Three new therapies, including an oral monotherapy currently under ANVISA evaluation, could significantly improve pharmaceutical services by enhancing distribution and addressing geographical disparities."

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

REAL-WORLD RETROSPECTIVE ANALYSIS OF PEGCETACOPLAN EFFECTIVENESS IN PATIENTS FROM CEE COUNTRIES WITH PNH AND NO OPTIMAL RESPONSE TO C5 INHIBITORS (EHA 2025) - "Pegcetacoplan therapy was indicated based on experiencing EVH during C5 inhibitor therapy (eculizumab n=19, ravulizumab n=6, crovalimab n=1). This is the only real-world analysis of the pegcetacoplan effectiveness in PNH patients from CEE countries, not responding optimally to C5 inhibitors. We confirmed the high efficacy of pegcetacoplan in a group of PNH patients experiencing EVH during C5 inhibitor therapy, especially in terms of improving hemoglobin levels and normalizing reticulocytosis with unchanged LDH values. Given the relatively small patient population of the registration study and the sparse data from single real-world analyses, this analysis provides valuable data on the effectiveness of pegcetacoplan therapy, particularly with detailed characteristics of BTH events and management strategies in real-world settings."

Real-world • Real-world evidence • Retrospective data • Cardiovascular • Hematological Disorders • Infectious Disease • Influenza • Pneumonia • Respiratory Diseases • Thrombosis

LP-005, A BIFUNCTIONAL C5 ANTIBODY FUSION PROTEIN, EFFECTIVELY CONTROLS BOTH HEMOLYSIS: INTERIM RESULTS FROM A PHASE 2 STUDY (EHA 2025) - "Eculizumab and Crovalimab are currently approved for treatment of patients with PNH, yet treatment limitations include hemolysis breakthrough for non-sufficient C5 inhibition, lack of efficacy in patients with C5 mutational variants, and the burden of regular intravenous infusions. The interim results of this phase 2 study demonstrate the safety and efficacy of LP-005 in both complement inhibitor-naïve or Eculizumab treated PNH patients. The clinical findings showed that LP-005 (bifunctional complement inhibitor) is potentially superior over single complement pathway inhibitors, making it potentially best-in-class and more convenient than current therapies."

P2 data • Anemia • Aplastic Anemia • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

CLINICAL FEATURES AND OUTCOMES OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS TREATED WITH ECULIZUMAB IN TAIWAN: A MULTICENTER RETROSPECTIVE ANALYSIS (EHA 2025) - "Prior treatments included steroids (29.4%), cyclosporine (18.9%), anti-thymocyte globulin (10.8%), danazol (24.2%), and one crovalimab trial participant...Adjuvant therapies for EVH associated with symptomatic anemia included rituximab (n=2), steroids (n=14), cyclosporine (n=6), and danazol (n=5)... Eculizumab effectively reduces intravascular hemolysis and improves survival in Taiwanese PNH patients, though BTH and transfusion-dependent treatment discontinuation remain challenges."

Retrospective data • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Disease • Rare Diseases • Renal Disease • Thrombosis

PiaSky Approved in Taiwan as First Subcutaneous Treatment for Paroxysmal Nocturnal Hemoglobinuria (Chugai Press Release) - "Chugai Pharmaceutical Co., Ltd...announced that Chugai Pharma Taiwan Ltd...obtained an orphan drug import drug license from the Taiwan Food and Drug Administration (TFDA) for Chugai’s PiaSky for 'for the treatment of the patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40 kg,' on May 19, 2025....This approval is based on the results of the Global Phase III COMMODORE 2 study in PNH patients who had not been previously treated with C5 inhibitors."

Approval • Paroxysmal Nocturnal Hemoglobinuria

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 2029 ➔ Sep 2027 | Trial primary completion date: Sep 2029 ➔ Sep 2027

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

COMMUTE-a: A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS) (clinicaltrials.gov) - P3 | N=83 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology

COMMUTE-p: A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS) (clinicaltrials.gov) - P3 | N=41 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Nephrology • Pediatrics

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=204 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2028 ➔ Sep 2027

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

Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice. (PubMed, Blood) - "In particular, BTH may occur with all complement inhibitors, with a frequency of 10-15% over 6 months with eculizumab, crovalimab, and pegcetacoplan, and <5% with ravulizumab, iptacopan, and danicopan plus anti-C5. Complement amplifying conditions were observed in about half of cases and were more frequently infections. Treatment adherence, optimization of the administration schedule, anticoagulant prophylaxis, as well as education of patients and physicians remain important factors to prevent BTH and its complications."

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

Advancing Landscape of Paroxysmal Nocturnal Hemoglobinuria Treatment. (PubMed, Turk J Haematol) - "With an improved understanding of PNH biology, a focused effort on complement inhibitors led to the discovery of eculizumab, a C5 inhibitor initially approved by the FDA in 2007. Further advancements in drug development for PNH include improved pharmacokinetics with ravulizumab in 2018 and the introduction of proximal complement inhibitors such as pegcetacoplan (2021), iptacopan (2023), and danicopan (2024), and crovalimab (2024) to enhance patient outcomes. With these new proximal and distal complement inhibitors in the treatment landscape, it is timely for clinicians to review the evolving landscape of PNH treatments and patient selection."

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

COMMODORE 1: Crovalimab demonstrates 2-year efficacy and safety in switch patients with paroxysmal nocturnal haemoglobinuria (BSH 2025) - No abstract available

Clinical • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

CROSSWALK-a: A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Participants With Sickle Cell Disease (SCD). (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Mar 2025 ➔ Dec 2024

Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Crovalimab: a new era in paroxysmal nocturnal hemoglobinuria management. (PubMed, Ann Med Surg (Lond)) - "Clinical trials such as COMMODORE 3 have shown crovalimab's effectiveness and high tolerability in PNH patients who have not previously used a C5 inhibitor. Crovalimab has been proven effective in maintaining hemoglobin levels, reducing the need for transfusions, and improving patient outcomes by inhibiting terminal complement activation."

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

FDA approval of crovalimab: a milestone in paroxysmal nocturnal hemoglobinuria treatment. (PubMed, Ann Med Surg (Lond)) - No abstract available

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

COMMODORE 3: A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition (clinicaltrials.gov) - P3 | N=51 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Feb 2028 ➔ Dec 2026

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

Current status and perspectives of hematopoietic cell transplantation in patients with paroxysmal nocturnal hemoglobinuria. (PubMed, Front Immunol) - "Non-transplant PNH therapies include anti-C5 monoclonal antibodies that reduce terminal complement activation (eculizumab, ravulizumab, and crovalimab) and proximal complement pathway inhibitors such as pegcetacoplan (C3 inhibitor), iptacopan (complement factor B inhibitor), and danicopan (complement factor D inhibitor)...In the case of severe aplastic anemia with an associated PNH clone, immunoablative protocols based on anti-thymocyte globulin serotherapy with fludarabine and cyclophosphamide are recommended. The use of reduced toxicity protocols with fludarabine has been well-documented in patients with classic PNH. A treosulfan/fludarabine-based regimen is recommended; however, there is no consensus on optimal drug selection."

Journal • Review • Aplastic Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Graft versus Host Disease • Hematological Disorders • Immunology • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Transplantation • CFB

Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria. (PubMed, Br J Clin Pharmacol) - "These data confirm an effective crovalimab-dosing regimen that achieves complete terminal complement activity inhibition and disease control in patients with PNH."

Journal • PK/PD data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria

CROSSWALK-a: A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Participants With Sickle Cell Disease (SCD). (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Hematological Disorders • Sickle Cell Disease