The pharmacokinetics (PKs) and biochemical efficacy are comparable for 3 alpha-1 proteinase inhibitor (A1PI) augmentation therapies for the treatment of alpha-1 antitrypsin deficiency (AATD).
The results of retrospective analyses of 3 previous clinical trials published in Pulmonary Therapy showed that the 3 A1PI augmentation therapies, Aralast® NP, Aralast™, and Prolastin®, have comparable biochemical efficacies and PKs.
“These retrospective analyses provide robust evidence that Aralast NP has biochemical efficacy and PK comparable to that of Aralast and Prolastin, supporting the use of any of these A1PI products for the treatment of patients with AATD,” the authors said.
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The first study analyzed (study 1) was a phase 3, multicenter, randomized, double-blind, controlled study that compared Aralast (formerly known as Respitin) to Prolastin in adult patients with congenital AATD.
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During the study, Aralast was given to 14 patients and Prolastin was given to another 13. No significant difference was observed after a single treatment infusion between the 2 treatments for baseline-corrected and uncorrected PK parameters including the maximum observed drug concentration (Cmax), the area under the concentration-time curve (AUC) from time 0 to the last measurable concentration (AUC0–t), and the terminal elimination phase half-life (t½).
Trough serum concentrations were also collected in 13 Aralast and 13 Prolastin patients from study 1 over multiple intravenous infusions. Both sets of patients demonstrated an increase in trough concentrations with repeated infusions before reaching a steady state. No significant difference was observed in the baseline-corrected or uncorrected values of antigenic or functional A1PI over 12 weeks.
The second study (study 2; NCT00242385) was a phase 1 trial that compared the PK values of adult patients with severe congenital AATD after a single dose of Aralast or Aralast NP. The mean Cmax, AUC0–t, and the AUC from time 0 to infinity (AUC0–inf) were all found to be comparable between the 2 treatments.
Study 3 (NCT00396006) was a phase 4 study designed to assess the safety and efficacy of Aralast NP in adult AATD patients with severe congenital AATD.
Using mean single-dose plasma concentrations and 90% confidence intervals of the means from study 2 along with nonparametric superpositioning, steady-state plasma concentration-time profile predictions were created for 10 consecutive weeks of Aralast NP infusions. These values were compared to the actual observed A1PI concentrations from studies 1 and 3 and were found to be comparable.
Reference
Li Z, Franke RM, Morris DN, Yel L. Pharmacokinetics and biochemical efficacy of an α1-proteinase inhibitor (Aralast NP) in α1-antitrypsin deficiency: A cross-product retrospective comparability analysis. Pulm Ther. Published online August 24, 2022. doi:10.1007/s41030-022-00199-4
