Home » Drug Information » FDA Approved Drugs » 2003
Medical Areas: Hematology | Pulmonary/Respiratory Diseases
View By:YearCompanyConditionsTherapeutic AreasDrug Names
Zemaira (alpha1-proteinase inhibitor)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Aventis Behring
Approval Status: Approved July 2003
Treatment Area: Alpha1-proteinase inhibitor deficiency
Zemaira is an intravenous therapy for alpha 1 proteinase
It is indicated for chronic augmentation and maintenance therapy
in individuals with alpha1-proteinase inhibitor (A1-PI) deficiency
and clinical evidence of emphysema. Safety and effectiveness in
pediatric patients have not been established.
FDA approval of Zemaira is based on a several pivotal studies
conducted on a total of 89 subjects with A1-PI deficiency. Subjects
ranged in age from 29 to 68 years with a median age of 49 years. In
one double blind, controlled clinical study, 44 subjects were
randomized to receive 60 mg/kg of either Zemaira or Prolastin once
weekly for 10 weeks. After 10 weeks, all subjects received Zemaira
for an additional 14 weeks. All subjects were followed for a total
of 24 weeks to complete the safety evaluation. The mean trough
serum A1-PI levels at steady state (Weeks 7-11) in the
Zemaira-treated subjects were statistically equivalent to those in
the Prolastin-treated subjects. The difference between the Zemaira
and the Prolastin groups was not considered clinically significant
and may be related to the higher specific activity of Zemaira.
In a subgroup of subjects enrolled in the study, bronchoalveolar
lavage was performed at baseline and at Week 11. Four A1-PI related
analytes in ELF were measured: antigenic A1-PI, A1-PI: NE
complexes, free NE, and functional A1-PI (anti-neutrophil elastase
capacity, ANEC). A blinded retrospective analysis of the study,
which revised the prospectively established acceptance criteria
showed that within each treatment group, ELF levels of antigenic
A1-PI and A1-PI:NE complexes increased from baseline to Week 11. No
clinically significant differences were detected between the two
Adverse events associated with the use of Zemaira may include
(but are not limited to) the following:
- Injection Site Pain
Mechanism of Action
Alpha1-proteinase inhibitor (A1-PI) deficiency is a chronic,
hereditary disorder that can cause severe tissue damage and death.
Pulmonary diseases, such as emphysema, are one of the main results
of A1-PI deficiency. Emphysema is caused by the
protease-antiprotease imbalance in the lungs which causes
inflammation and tissue damage. A1-PI is the primary antiprotease
in the lower respiratory tract, where it inhibits neutrophil
elastase (NE), an enzyme that destroys pulmonary tissue. Those
individuals without A1PI deficiency produce sufficient A1-PI to
control the NE produced by activated neutrophils and are thus able
to prevent inappropriate damage to lung tissue by NE.
Zemaira acts to increase and maintain serum levels and lung
epithelial lining fluid (ELF) levels of A1-PI. Low blood levels of
A1-PI are also associated with liver disease and liver
Dunn M, Stiskal J, O'Brien K, Ito S, Cox DW, Kelly
E, Shennan A et al. Proteinase inhibitor (A1PI) therapy
for the prevention of chronic lung disease of prematurity (CLD) - a
dose ranging study and meta analysis with previous randomized
clinical trial (RCT). Pediatr Res 2000:397A.
Laurell CB, Eriksson S. The electrophoretic
alpha1 globulin pattern of serum in alpha1 antitrypsin deficiency.
Scand J Clin Lab Invest 15:132-140, 1963.
Stoller JK. Alpha1-antitrypsin deficiency and
augmentation therapy in emphysema. Clev Clin J Med 56:
Stone PJ, Morris TA, Franzblau C, et al.
Preliminary evidence that augmentation therapy diminishes
degradation of cross-linked elastin in alpha1 antitrypsin deficient
humans. Respiration 62:76-79, 1995.