Trial reportBritish journal of clinical pharmacology2025
Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria.
Trial report in British journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed.
- Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria.British journal of clinical pharmacology · 2025Trial
- Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH): Pooled Results From the Phase 3 COMMODORE Studies.European journal of haematology · 2025Trial
- Exploring individualized crovalimab dosing in PNH through in silico modelling: Potential for improved convenience and cost efficiency.British journal of clinical pharmacology · 2026Article
- Systems Pharmacology Approach to Paroxysmal Nocturnal Hemoglobinuria: Quantitative Framework for Biomarker Dynamics across Multi-Mechanistic Therapies.Clinical pharmacology and therapeutics · 2026Article
- Article
- A Quantitative Approach to Guiding Target Antigen Selection and Antibody Optimization in Recycling Antibody Discovery.The AAPS journal · 2025Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
aimsCrovalimab is a novel C5 inhibitor administered first intravenously and then subcutaneously in patients with paroxysmal nocturnal haemoglobinuria (PNH) naive to complement inhibition or switching from eculizumab or ravulizumab. Crovalimab showed efficacy and safety comparable to eculizumab in the pivotal COMMODORE 2 and supporting studies.
methodsWe characterized crovalimab pharmacokinetics and the relationship between exposure pharmacokinetic parameters and pharmacodynamic biomarkers, efficacy and safety endpoints using pooled data (healthy volunteers [n = 9], naive [n = 210] and switched [n = 211] patients). Pharmacodynamic biomarkers included 50% complement activity and free C5; normalized lactate dehydrogenase was a marker of haemolysis. Adverse events (AEs) of special interest, related serious AEs, related Grade ≥3 AEs and infections were assessed.
resultsThere was no clinically relevant difference in crovalimab concentrations between naive and switch patients. Bodyweight had a statistically significant impact on crovalimab clearances and volumes of distribution. Thus, the recommended dosing regimen used weight-based, two-tiered dosing (100 kg cutoff). Age did not have a clinically meaningful impact on crovalimab exposure. In COMMODORE 2, and the supporting COMMODORE 1 and 3 studies, complete terminal complement activity inhibition was achieved immediately at the end of the initial intravenous infusion and sustained throughout the treatment period in ≥97% of patients. Crovalimab concentrations above ≈100 μg/mL achieved complete inhibition of terminal complement activity, resulting in disease control with normalized lactate dehydrogenase ≤1.5 × upper limit of normal (ULN). There was no increased risk of AEs at higher exposure.
conclusionsThese data confirm an effective crovalimab-dosing regimen that achieves complete terminal complement activity inhibition and disease control in patients with PNH.
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