To evaluate the biochemical efficacy and safety of a new source of highly purified, plasma derived alpha1-proteinase inhibitor (A1-PI) in individuals with alpha1-antitrypsin (AAT) deficiency.
A randomized, double-blind study compared Zemaira® (ZLB Behring LLC) [Z] with Prolastin® (Bayer Corporation) [P]. Patients received either Z or P (randomized 2:1) for 10 weeks by intravenous infusion (60 mg/kg functionally active A1-PI weekly). The P group was then crossed over to an open-label phase where all subjects received Z for 14 weeks. A subset of 15 patients with forced expiratory volume in 1 second ≥50% predicted underwent bronchoalveolar lavage. Antigenic AAT levels and AAT:neutrophil elastase (AAT:NE) complexes in the epithelial lining fluid (ELF) between baseline and Week 11 were measured by ELISA.
Increases in ELF AAT levels were statistically significant in both treatment groups. Subjects receiving Z A1-PI had ELF values of 197.1 nM at baseline, increasing to 1125.5 nM after 10 weeks of treatment (p<0.0001), and those receiving P increased from 261.5 nM to 1192.5 nM (p=0.0121). Z A1-PI remained functionally active when delivered to the lung from the systemic circulation, as indicated by significant increases in ELF AAT:NE complexes from baseline to 11 weeks [2.8 nM to 66.8 nM (p=0.0012)]. Both Z and P were safely tolerated.
The results indicate that both protein preparations are delivered to the lung in an equivalent manner after intravenous administration and that the exogenous protein is in a functional state capable of forming complexes with NE in the lung.
Z intravenous augmentation therapy is associated with reconstitution of lower respiratory protease-anti-protease homeostasis similar to P.
AUC variable (μM*day)Median (range)Ratio of Z(A1-PI): P(A1-PI)90% CIZ(A1-PI)P(A1-PI)AUD0-21129 (93 –171)140 (101 –194)92.4%88.5% - 96.5%AUD0-∞134 (96 –190)147 (104 - 214)92.0%84.9% - 99.7%
L Spencer, Consultant fee, speaker bureau, advisory committee, etc. LTS and MB have been scientific advisors to Aventis Berhing and Bayer Healthcare.; Other DPP and JMS have no financial disclosures.