Talecris Biotherapeutics (Nasdaq: TLCR) announced today the publication of combined data from two studies demonstrating that augmentation therapy with Alpha(1)-Proteinase Inhibitor (Human) (A1PI) significantly reduces lung tissue loss in patients with emphysema related to Alpha(1)-antitrypsin (AAT) deficiency. Results of the studies, published as an integrated analysis of the raw data from two similar pilot trials, were published in the journal Respiratory Research. (http://respiratory-research.com/content/11/1/136)
AAT deficiency is a rare, genetic disease in which low levels of the AAT protein circulating in the lungs can increase an individual's risk of developing emphysema. Treatment with A1PI therapy augments or increases the levels of this protein in the lungs.
Two randomized, double-blind, placebo-controlled clinical trials investigated the effect of A1PI therapy on emphysema progression using change in lung density as a measure. Lung density is a validated and specific measure of tissue loss in emphysema that relates well to physiological and clinical features of the disease.
Although the two studies used different intravenous dosing regimens, they were comparable in treatment duration, patient characteristics and the use of computed tomography (CT) to study lung density. The similar characteristics of the studies allowed the pooling of the individual patient data, which increased the robustness of the analysis. An analysis of the data from both studies was conducted by Professor Robert A. Stockley, Birmingham, UK, and Professor Asger Dirksen, Hellerup, Denmark.
The results of the integrated analysis demonstrated a mean change in lung density from baseline to the final CT scan of -4.082 g/L for the AAT treatment group and -6.379g/L for the placebo group, a statistically significant difference of 2.297 (95% CI, 0.669 to 3.926; p = 0.006).
"The mean data from the integrated analysis demonstrate a deceleration of lung tissue loss with AAT augmentation therapy versus placebo with statistical significance," said Stockley.
The effect of augmentation therapy with any Alpha(1)-proteinase inhibitor (A1PI) on pulmonary exacerbations and on the progression of emphysema in Alpha(1)-antitrypsin deficiency has not been demonstrated in a single, prospective, randomized, controlled clinical trial.
The two clinical trials included in the integrated analysis were a three-year Danish-Dutch study of 56 patients (http://ajrccm.atsjournals.org/cgi/content/full/160/5/1468) and the EXAcerbations and CT scan as Lung Endpoints (EXACTLE) trial of 77 patients over 24 to 30 months (http://erj.ersjournals.com/content/33/6/1345.full). In both trials, patients were randomized to receive infusions of A1PI or a placebo. The results suggested a trend toward reduction in emphysema progression with A1PI therapy, as measured by CT densitometry. The trials were not powered to show efficacy; thus neither trial reached statistical significance on its own. Pooling the data increased the number of patients and the statistical power of the analysis.
Talecris Biotherapeutics, manufacturer of PROLASTIN®-C (Alpha(1)-Proteinase Inhibitor [Human]), funded the integrated analysis and the EXACTLE trial included in the analysis.