Fit-for-purpose validation of a drug-tolerant immunogenicity assay for a human mAb drug in animal safety studies.

A modified biotin-drug extraction and acid dissociation (BEAD) immunogenicity assay was developed to detect anti-drug-antibodies (ADA) against the human anti-FXIIa monoclonal antibody (mAb) drug, Garadacimab (previously called CSL312). Multiple strategies were tested to optimize the signal-to-background (S/B) ratio, assay sensitivity and the drug tolerance. The modified BEAD assay was found to be highly drug tolerant (>500 μg/ml) with a sensitivity of 100 ng/ml, in line with current FDA regulatory guidelines.

Airway inflammation and dysbiosis in antibody deficiency despite the presence of IgG.

Background: Patients with antibody deficiency suffer chronic respiratory symptoms, recurrent exacerbations, and progressive airways disease despite systemic replacement of IgG. Little is known about the respiratory tract biology of these patients.

Objective: We sought to measure immunoglobulin levels, inflammatory cytokines, and mediators of tissue damage in serum and sputum from patients with antibody deficiency and healthy controls; to analyze the respiratory microbiome in the same cohorts.

Pharmacokinetics and pharmacodynamics of a recombinant fusion protein linking activated coagulation factor VII with human albumin (rVIIa-FP) in patients with congenital FVII deficiency.

Recombinant fusion protein linking activated factor VIIa to human albumin (rVIIa-FP) is a therapeutic option designed to prevent and treat bleeding events in patients with congenital FVII deficiency with reduced infusion frequency compared to current FVII treatments. This study characterized the pharmacokinetics (PK) and pharmacodynamics (PD) of rVIIa-FP. A phase I multicenter, randomized, open-label, parallel-arm, single-dose study (NCT02470871) was conducted in nine patients with severe congenital FVII deficiency.

Population pharmacokinetics of subcutaneous C1-inhibitor for prevention of attacks in patients with hereditary angioedema.

Background: Long-term prophylaxis with subcutaneous (SC) administration of a highly concentrated plasma-derived C1-esterase inhibitor (C1-INH) formulation was recently approved by the Food and Drug Administration for hereditary angioedema (HAE) attack prevention.

Objective: To characterize the population pharmacokinetics of C1-INH (SC) (HAEGARDA ; CSL Behring) in healthy volunteers and HAE patients, and assess the variability and influence of covariates on pharmacokinetics.

Methods: C1-INH functional activity data obtained after administration of various C1-INH (intravenous; IV) and C1-INH (SC) doses from 1 study in healthy volunteers (n = 16) and 2 studies in subjects with HAE (n = 108) were pooled to develop a population pharmacokinetic model (NONMEM v7.