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Biochemical Efficacy and Safety of a New Pooled Human Plasma ₁-Antitrypsin, Respitin^*

^* From the Department of Pulmonary and Critical Care Medicine (Drs. Stoller and Dweik), Cleveland Clinic Foundation, Cleveland, OH; Pulmonary-Critical Care Branch (Mr. Rouhani), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD; University of Florida College of Medicine (Dr. Brantly), Gainesville, FL; Alpha Therapeutic Corporation (Ms. Shahin and Dr. Norton), Los Angeles, CA; University of Texas Health Center (Dr. Stocks), Tyler, TX; University of California San Diego (Dr. Clausen), San Diego, CA; and University of Utah Health Sciences Center (Dr. Campbell), Salt Lake City, UT.

Correspondence to: James K. Stoller, MS, MD, FCCP, Department of Pulmonary and Critical Care Medicine, A 90, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195; e-mail: stollej{at}ccf.org

Background: Augmentation therapy with pooled human plasma-derived ₁-antitrypsin (AAT) has been shown to have biochemical efficacy in restoring serum AAT levels above the protective threshold. Also, clinical efficacy has been suggested.

Objective: To evaluate the bioequivalence of a new solvent detergent-treated preparation of pooled human plasma-derived AAT (proposed name Respitin; Alpha Therapeutic Corporation; Los Angeles, CA) to the commercially available preparation (Prolastin; Bayer Corporation; West Haven, CT), we conducted a randomized controlled trial.

Methods: Eligible subjects were adults (> 18 years of age) who had never smoked or were ex-smokers, had severe deficiency of AAT, and had fixed airflow obstruction (ie, postbroncholdilator FEV₁ of 30 to 80% of predicted values and/or diffusing capacity of the lung for carbon monoxide [DLCO] of < 70% of predicted values with evidence of emphysema on a CT scan). Of the 28 subjects recruited, 26 completed the 12-week comparison. Participants were randomized to receive Respitin (60 mg/kg once weekly; 14 subjects) or Prolastin (60 mg/kg once weekly; 14 subjects), and recipients of Prolastin then crossed over to receive Respitin thereafter for the 24-week duration of the study.

Results: The primary efficacy criteria were satisfied for equivalence to comparator (ie, the ratio of mean trough serum levels for Respitin/Prolastin at weeks 8 to 11 exceeded the efficacy criterion [0.905; p = 0.0206] as did the slope of the mean trough level over weeks 11 to 23 [-0.003 µmol per week]). In Respitin recipients, the trough serum antineutrophil elastase capacity at week 7 and at weeks 8 to 11 was also equivalent to the comparator, as was the rise in AAT levels in epithelial lining fluid from baseline to week 7. The levels of urinary elastin degradation products showed little appreciable change for > 24 weeks, and no difference between compared groups was shown through week 12. Adverse events were similarly infrequent in compared groups. Finally, neither spirometry measurements nor DLCO showed a significant change through 24 weeks.

Conclusions: We conclude that this new solvent detergent-treated pooled human plasma-derived AAT (Respitin) demonstrates biochemical equivalence to Prolastin and that this new drug is well-tolerated.

Key Words: ₁-antitrypsin deficiency • antiprotease • efficacy • safety

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