"Recombinant Alpha 1-Antitrypsin Shows Promise in Treating AAT Deficiency: Presented at ERS"
 

COPENHAGEN, DENMARK -- September 26, 2005 -- Treatment with recombinant alpha 1-antitrypsin (AAT) results in increased levels of AAT in the epithelial lining fluid (ELF) of the lungs of individuals with congenital AAT deficiency, according to investigators who presented their findings here September 19[^th at the European Respiratory Society 15^th Annual Congress (ERS).

"We noted a dose response in AAT in patients' ELF," said David Gelmont, MD, medical director of global research and development, Baxter BioScience, Westlake Village, California. However, he cautioned that the findings are preliminary, because the study size was small and the study design did not include a control arm.

According to Dr. Gelmont, the current treatment, intravenous administration of plasma AAT, is expensive and tedious, while recombinant AAT is delivered by inhalation in an aerosolized format.

Dr. Gelmont and co-investigators wanted to see if 15 subjects with severe congenital AAT deficiency, defined as less than 15% of normal, would respond to recombinant AAT.

They conducted a randomized, open-label, dose-ranging study, in which they sought to determine the effects of different doses and regimens of aerosolized recombinant AAT on lower respiratory ELF analytes and cytokines.

Subjects received 7 days of treatment consisting of 1 of 3 dosing regimens: 100 mg daily, 100 mg twice daily, or 200 mg daily. The investigators obtained bronchoalveolar lavage samples at baseline and on day 8. The final sample was collected 12 to 24 hours after the last treatment.

The investigators detected a dose response for AAT, for AAT-human neutrophil elastase (HNE) complexes, and antineutrophil elastase capacity (ANEC) levels in the bronchoalveolar lavage fluid. The mean change in the AAT levels was 2,130 nM for the 100-mg daily group, 3,429 nM for the 100-mg twice-daily group, and 4,036 for the 200-mg daily group.

The investigators noted 18 cases of treatment-related adverse events, typically fever, chills, and nausea. They also noted non-dose-related decreases in pulmonary function tests and changes in the bronchoalveolar cytology. In 4 patients there was an increase in the eosinophil concentration and 6 patients had an increase in the polymorphonuclear concentrations.

The study was funded by Baxter Pharmaceuticals.

[Presentation title: A Phase 1B/2A Study to Evaluate the Effect of Aerosolized, Recombinant Alpha 1-Antitrypsin (rAAT) on Epithelial Lining Fluid (ELF) Analytes in Subjects With AAT Deficiency. Abstract 1919]
 

Source
"Recombinant Alpha 1-Antitrypsin Shows Promise in Treating AAT Deficiency: Presented at ERS" The Doctor's Guide 1995-2005, 26 September 2005, <http://www.docguide.com/news/content.nsf/news/8525697700573E18852570880067003B>