Pharmacokinetics and Biochemical Efficacy of an α1-Proteinase Inhibitor (Aralast NP) in α1-Antitrypsin Deficiency: a Cross-Product Retrospective Comparability Analysis.
Zhaoyang Li, Ryan M Franke, Denise N Morris, Leman Yel
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引用次数: 1
Abstract
Introduction: Augmentation therapy with plasma-derived α1-proteinase inhibitor (A1PI) products is currently the only approved disease-specific therapy for α1-antitrypsin deficiency (AATD), a genetic disorder associated with decreased levels of A1PI. Systemic trough levels of A1PI in plasma or serum are widely accepted as a biochemical efficacy endpoint in clinical trials for A1PI products.
Methods: Retrospective analyses utilizing data from three clinical studies in patients with AATD were conducted to evaluate the pharmacokinetic(s) (PK) and biochemical efficacy comparability of Aralast NP and two other A1PI augmentation therapies, Aralast and Prolastin. All three A1PI products were administered as either single or multiple 60 mg/kg intravenous infusions. PK and biochemical efficacy comparability analyses were conducted by evaluating antigenic and functional A1PI serum or plasma concentration data from each of the three studies.
Results: Comparable PK parameters were demonstrated between the three products for antigenic A1PI levels following a single infusion, with baseline-corrected and uncorrected geometric mean ratios for peak and systemic exposure ranging from 89.0% to 99.6%, with 90% confidence intervals within the 80-125% reference interval for bioequivalence. Biochemical efficacy comparability analyses of Aralast and Prolastin after multiple infusions at steady state showed geometric mean ratios for uncorrected and baseline-corrected antigenic and functional A1PI trough concentrations over weeks 8-11, and for individual weeks, that ranged from 75.8% to 106.6%, with the majority of the 90% confidence intervals falling either within the 80-125% interval or in proximity to it. Nonparametric superpositioning at steady state suggested that predicted trough concentrations for Aralast NP were comparable to the observed concentrations for Aralast and Prolastin.
Conclusion: 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.
Trial registration numbers: ClinicalTrials.gov identifiers, NCT00242385 and NCT00396006.
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Aims and Scope
Pulmonary Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the use of pulmonary therapies, devices, and surgical techniques.
Areas of focus include, but are not limited to: asthma; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; pulmonary hypertension; cystic fibrosis; lung cancer; respiratory tract disorders; allergic rhinitis and other respiratory allergies; influenza, pneumococcal infection, respiratory syncytial virus and other respiratory infections; and inhalers and other device therapies.
The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Pulmonary Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals.
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The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of pulmonary therapies.
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