Alpha-1 Antitrypsin Deficiency (AATD)


Aralast NP, also known as alpha1-proteinase inhibitor (A1-PI), is a stable, sterile, lyophilized preparation of purified human alpha1-antitrypsin prepared from large pools of human plasma in a cold ethanol fractionation process. Aralast NP contains the same active components of plasma A1-PI as Aralast, with formulations identical to those of Aralast. The ethanol fractionation process is followed by purification steps that include zinc chloride and polyethylene glycol precipitations and ion exchange chromatography. Aralast NP, which is licensed in the United States, contains A1-PI-derived products with chemical modifications that arise during manufacturing and occur in levels that vary from product to product. Aralast NP contains 2% A1-PI with truncated C-terminal lysine (removal of Lys394), whereas Aralast contains 67% A1-PI with truncated C-terminal lysine. No clinical data showing the effect of these structural modifications on the functional activity and immunogenicity of A1-PI are available. During the manufacturing process of these drugs, enveloped viral agents such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are inactivated by means of treatment with a solvent/detergent (S/D) mixture (tri-n-butyl phosphate and polysorbate 80). In addition, nanofiltration steps are taken to reduce the risk for the transmission of enveloped and non-enveloped viral agents. Studies conducted in vitro have shown that various viruses, such as the bovine viral diarrhea virus (BVDV), a model for hepatitis C virus, and other lipid-enveloped RNA viruses are inactivated during the production of Aralast NP.1

Warnings and Precautions

Aralast NP can cause hypersensitivity reactions because it may contain trace amounts of immunoglobulin A (IgA). Severe anaphylactic and hypersensitivity reactions may develop in patients with known antibodies to IgA. The vital signs of such patients should be monitored throughout the infusion process. Emergency treatment should be administered to patients who have hypersensitivity reactions during the infusion process. For the treatment of acute anaphylactic and anaphylactoid reactions, epinephrine and other supportive therapy should be ready at hand. There is a risk for the transmission of infectious agents with Aralast NP. Some commonly transmitted agents are the virus that causes Creutzfeldt-Jakob disease (vCJD) and other emerging viruses and pathogens. Screening of plasma donors for infectious agents reduces the risk of transmitting certain viruses. However, human pathogenic agents may be transmitted despite the precautions taken. In clinical studies, no HIV, HBV, and HCV seroconversions were reported with the use of Aralast NP.2   

Indications and Dosage

Aralast NP is indicated for chronic augmentation therapy in adults with clinically evident emphysema due to congenital alpha1-antitrypsin deficiency (AATD). It increases antigenic and functional (anti-neutrophil elastase capacity [ANEC]) serum levels and antigenic lung epithelial lining fluid levels of A1-PI. The efficacy of augmentation therapy with A1-PIs, including Aralast NP, on pulmonary exacerbations and the progression of emphysema in AATD has not yet been demonstrated conclusively in randomized controlled clinical trials. Long-term effects of Aralast NP and Aralast during maintenance therapy and chronic augmentation are not yet available. Aralast NP is not recommended for patients who have lung disease without confirmed congenital A1-PI deficiency.3 

The generic name of Aralast NP is alpha1-proteinase inhibitor (human). It is effective for the treatment of lung diseases like emphysema and certain inherited diseases due to A1-PI deficiency. Lung damage in patients is caused by elastase, a naturally occurring substance in the body that is required to eliminate bacteria in the lungs. The A1-PI protein stops elastase activity in the body when it is no longer needed. In individuals with insufficient amounts of A1-PI, excess elastase can cause lung damage. Aralast NP has the potential to replace missing A1-PIs and prevent further lung damage. Side effects of Aralast NP include sore throat, drowsiness, muscle aches, fever, and dizziness. Patients should inform their healthcare provider if they experience unusual fatigue, drowsiness, yellowing of the eyes or skin, dark urine, persistent nausea, or vomiting. Aralast NP is prescribed by doctors after the potential benefits are weighed against risks. The likelihood of parvovirus B19 and hepatitis virus infections is small. Any patient who receives ​​Aralast NP should seek immediate medical attention if a serious allergic reaction develops, with symptoms like difficult breathing, chest tightness, itching or swelling, and hives.4

Clinical Trial: Efficacy of Aralast NP A1-PI Augmentation Therapy

A double-blind, prospective, randomized clinical study is to be conducted to evaluate the efficacy and safety of Aralast NP as A1-PI augmentation therapy at doses of 60 and 120 mg/kg. Enrolled patients have A1-PI deficiency and chronic obstructive pulmonary disease-emphysema (COPD-E). Aralast NP A1-PI augmentation therapy at 60 or 120 mg/kg of body weight per week is compared with placebo. The loss of emphysematous lung tissue in participants with COPD-E and A1PI deficiency is evaluated by measuring change in lung density. Adults 18 to 65 years of age at the time of a diagnosis of A1-PI deficiency are eligible to participate. Diagnostic criteria include an endogenous plasma A1-PI level below 11 micromoles (μM). An interval of at least 4 weeks before the start of treatment is required to remove any previous dose of A1-PI augmentation therapy. Screening of plasma A1-PI levels is to be repeated in participants with inadequate washout of prior augmentation therapy. Participants are also required to have a documented A1-PI genotype. A1-PI genotyping is to be offered at the time of screening. Participants in the clinical trial are screened according to the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). They are required to have a forced expiratory volume in 1 second (FEV1) greater than 35% and less than 70% predicted. If the patients have been treated with any respiratory medications, such as inhaled bronchodilators, inhaled corticosteroids, or systemic corticosteroids, the dose should have remained stable for at least 28 days before screening. The primary outcome of the study is the annual rate of physiologically adjusted lung density change, measured as the 15th percentile of the lung density measurements as assessed for patients with AATD by computed tomography (CT) densitometry at total lung capacity. Changes in the adjusted lung density of patients who received Aralast NP at 60 or 120 mg per kilogram of body weight per week will be compared with those in the placebo group.5    

References

  1. Aralast NP: alpha1-proteinase inhibitor (human). Food and Drug Administration. Accessed August 23, 2021.
  2. Aralast NP: alpha-1-proteinase inhibitor – human kit. DailyMed. Accessed August 23, 2021.
  3. Aralast NP: alpha1-proteinase inhibitor (human) liquid for intravenous infusion. RxList. Accessed August 23, 2021.
  4. Aralast NP vial. WebMD. Accessed August 23, 2021
  5. ARALAST NP Alpha-1 Lung Density Chronic Obstructive Pulmonary Disease-Emphysema (COPD-E) Study. Cochrane Library. Accessed August 23, 2021.

Reviewed by Harshi Dhingra, MD, on 8/30/2021.