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 (ISN-WCN 2026) - P3 | "Established C5 inhibitors (C5is), eculizumab and ravulizumab, are effective but burdensome treatments, requiring intravenous infusions every 2 or 8 weeks, respectively. These results support crovalimab's long-term benefits. The ongoing COMMUTE-a and COMMUTE-p trials evaluating crovalimab in aHUS continue to assess fatigue with the FACIT-Fatigue PRO measure, given its importance in this population.This abstract was previously submitted to European Society for Paediatric Nephrology 2024."

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

CROVALIMAB: PATIENT PREFERENCES AND ONGOING PHASE III COMMUTE TRIALS IN ATYPICAL HAEMOLYTIC URAEMIC SYNDROME (AHUS) (ISN-WCN 2026) - P3 | "Pts were randomised to receive crova (weight-based tiered dosing regimen: loading doses and SC Q4W maintenance) or eculizumab (ecu; 900 mg IV Q2W) over 24 weeks. Top reasons for crova preference over ecu were: fewer hospital visits required, easier administration, less time needed to administer and better quality of life.COMMUTE-a and COMMUTE-p are recruiting in 19 and 14 countries, respectively.Conclusion Most pts with PNH in COMMODORE 1 and 2 preferred crova to ecu, largely due to faster, easier administration. COMMUTE trials are currently enrolling pts with aHUS.This abstract was previously submitted to ERA 2024."

Clinical • P3 data • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Paroxysmal Nocturnal Hemoglobinuria

Year Crovalimab Paroxysmal Nocturnal Haemoglobinuria (PNH) Data for Fatigue, a Relevant Symptom in Atypical Haemolytic Uraemic Syndrome (aHUS) and PNH (PAS 2026) - No abstract available

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

Low Risk for Meningococcal Infections with Systemically Administered Pegcetacoplan, a Complement C3 and C3b Inhibitor (THSNA 2026) - P3 | "Clinical benefits of the initially available C5 inhibitors that block terminal complement activation (eculizumab, ravulizumab, crovalimab) paved the way for the development of proximal inhibitors, including the C3/C3b inhibitor pegcetacoplan, the factor B inhibitor iptacopan, and the add-on (to C5 inhibitors) factor D inhibitor danicopan. Understanding the safety profile of pegcetacoplan and other complement-targeted therapies will help physicians and patients make informed treatment decisions for individuals with complement-mediated conditions. For over 7 years of total systemic pegcetacoplan exposure, no cases of encapsulated N. meningitidis and consistently low rates of infections by other encapsulated bacteria were observed in patients with PNH, C3G, primary IC-MPGN, or other conditions. These findings may reflect effective risk mitigation strategies."

Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Immunology • Infectious Disease • Influenza • Lupus Nephritis • Meningococcal Infections • Nephrology • Paroxysmal Nocturnal Hemoglobinuria • Pneumococcal Infections • Pneumonia • Primary Immunodeficiency • Rare Diseases • Respiratory Diseases • Septic Shock

Clinical Characteristics of 30 Cases of Childhood Haemolytic Uremic Syndrome in a Single Centre. (PubMed, Nephrology (Carlton)) - "Childhood HUS in this cohort is dominated by aHUS and secondary types. Early etiological differentiation, comprehensive laboratory assessment and targeted therapy improve outcomes, with findings aligning with global data but showing a more pronounced female bias due to high SLE-related cases."

Journal • Acute Kidney Injury • Atypical Hemolytic Uremic Syndrome • Chronic Kidney Disease • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Nephrology • Renal Disease • Systemic Lupus Erythematosus • Transplantation • HP

Comparative Efficacy of Complement Inhibitors in Complement Inhibitor-Naïve PNH: A Systematic Review With Supportive Exploratory Network Meta-Analysis of Randomized Trials. (PubMed, EJHaem) - "A total of four randomized controlled trials evaluating four complement inhibitor agents (ravulizumab, crovalimab, eculizumab and pegcetacoplan) were included in this systematic review and network meta-analysis, involving 589 complement inhibitor-naïve adults with PNH. However, the evidence network is sparse (four trials) and the cross-trial differences limit reliable inference regarding relative efficacy between active agents. Comparative findings should be interpreted as hypothesis-generating."

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

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

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jul 2025 ➔ Jan 2031 | Trial primary completion date: Jul 2025 ➔ Oct 2030

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

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Jan 2020 ➔ Jul 2025

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

A Study to Evaluate Crovalimab in People With Antiphospholipid Syndrome (APS) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Hoffmann-La Roche | N=300 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Genetic Disorders • Hematological Disorders

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=49 | Recruiting | Sponsor: Hoffmann-La Roche | N=39 ➔ 49

Enrollment change • First-in-human • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria

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=49 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jan 2031 ➔ Jun 2031 | Trial primary completion date: Oct 2030 ➔ Mar 2031

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

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=49 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Feb 2018 ➔ Aug 2018

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

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=49 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jan 2021 ➔ Oct 2020 | Trial primary completion date: Jan 2021 ➔ Oct 2020

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

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=49 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jul 2020 ➔ Jan 2021 | Trial primary completion date: Aug 2018 ➔ Jan 2021

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

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

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=49 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2020 ➔ May 2023 | Trial primary completion date: Sep 2020 ➔ Jan 2020

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

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Crovalimab as Add-On Therapy in Patients with Antiphospholipid Syndrome and Recurrent Thrombosis (LUPUS 2026) - No abstract available

Clinical • P2 data • Immunology

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2023 ➔ May 2025

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

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=49 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • First-in-human • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2031 ➔ Jan 2026 | Trial primary completion date: Mar 2031 ➔ Jan 2026

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

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jan 2026 ➔ Sep 2026 | Trial primary completion date: Jan 2026 ➔ Sep 2026

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

Improvement in anemia and symptoms after switching from crovalimab to iptacopan in paroxysmal nocturnal hemoglobinuria. (PubMed, Hematology) - "A 72-year-old man with long-standing PNH received eculizumab followed by crovalimab. This case demonstrates the feasibility of switching from crovalimab to iptacopan despite the absence of an established method, and pharmacokinetic considerations guided the timing. Switching to iptacopan led to rapid and durable improvement in anemia and symptoms, supporting proximal complement inhibition as a valuable option for PNH patients inadequately controlled with C5 inhibitors."

Journal • Anemia • Complement-mediated Rare Disorders • Gastrointestinal Disorder • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Disease • Rare Diseases

R&D activities: Hematology (Chugai Press Release) - "We decided to remove a pH-dependent binding humanized anti-complement (C5) monoclonal antibody SKY59/RG6107 (Product name: PiaSky) for the treatment of sickle cell disease from the pipeline following the decision made by Roche to discontinue the development, considering the results of overseas study."

Discontinued • Sickle Cell Disease