Regulatory Decision Summary for Prolastin-C Liquid / Prolastin-C

Authorization was based on the results from a single pharmacokinetics clinical trial in patients with Alpha1-Antitrypsin Deficiency. The study (GT11402) was a Multi-center, Randomized, Double-blind, Crossover Study enrolled 32 subjects to assess the safety and pharmacokinetics of Liquid Alpha1-Proteinase Inhibitor (Human) compared to Prolastin-C in Subjects with Alpha1-Antitrypsin Deficiency (AATD). Clinical safety, immunogenicity, and pharmacokinetics (PK) of weekly infusions of 60 mg/kg Liquid Alpha1-PI were compared to 60 mg/kg of Prolastin-C.

The primary PK endpoint for bioequivalence was based on the antigenic assay, the functional anti-neutrophil elastase capacity (ANEC) assay, and functional A1-PI assay results. The primary endpoint was met in this study. The study demonstrated similarity of pharmacokinetic profiles between Prolastin-C Liquid and the approved lyophilized dosage form of Prolastin-C at steady-state.

The safety objective of this study was to evaluate Liquid Alpha1-PI 60 mg/kg, given in weekly infusions over 8 weeks, vs Prolastin-C 60 mg/kg, given in weekly infusions over 8 weeks, in subjects with AATD.

A safety assessment of alanine as an excipient showed that the safety margins are sufficient to conclude that administration of 60 mg/kg Prolastin-C Liquid does not pose a toxicity risk for humans.

The safety profile of Prolastin-C Liquid administered weekly at 60 mg/kg is consistent with that of the approved Prolastin-C in lyophilized dosage form.

Prolastin-C Liquid does not require reconstitution during its preparation for use, unlike lyophilized formulations of alpha1-PI which must be reconstituted with sterile water in the clinic or hospital. Thus, the potential for reconstitution errors are eliminated, and preparation time is shortened.

The benefit/risk profile of Prolastin-C Liquid was therefore deemed favourable.