Alpha-1 Antitrypsin Deficiency Treatment Has Meant a Weekly Infusion Since 1987, and a One-Time Gene Edit Is Now Testing That

Alpha-1 antitrypsin deficiency is usually found late. The person is often in middle age, short of breath on stairs, and has been told for years that it is asthma or ordinary COPD. MedlinePlus notes that many people with the condition are undiagnosed and some are misdiagnosed with asthma, and Beam Therapeutics estimates that only about 10% of the more than 100,000 Americans with the most severe form have been diagnosed. The ones who do get the diagnosis are then offered a treatment that has barely changed in almost 40 years.

Alpha-1 antitrypsin (AAT) is a protein the liver makes to protect the lungs. It neutralizes an enzyme called neutrophil elastase that white blood cells release to fight infection, which would otherwise digest the elastic tissue of the lung. In alpha-1 antitrypsin deficiency (AATD), variants in both copies of the SERPINA1 gene, most often 2 copies of the one called Z, make the protein misfold. Too little reaches the lungs, so they wear out early into emphysema, and the misfolded protein piles up in the liver, where it can cause scarring. Normal blood levels are 20 to 53 micromolar (GeneReviews); people with the PiZZ genotype typically run around 5 (Zemaira label; Beam Therapeutics, 2026).

Prolastin-C, Aralast NP, Zemaira and Glassia Compared, and Why the Choice Is Mostly Practical

All 4 augmentation products are purified human alpha-1 proteinase inhibitor, all use the same 60 mg per kilogram weekly dose, and all carry the same core warnings in their FDA labels: they are not for people with IgA deficiency who have antibodies against IgA, they can cause allergic reactions including anaphylaxis, and because they are made from human plasma they may carry a risk of transmitting infectious agents such as viruses. The differences are about handling, which matters when you do this 52 times a year.

Prolastin-C Liquid (Grifols)

The original product line, first approved in 1987. A ready-to-use liquid in 500 mg, 1,000 mg and 4,000 mg vials, stored in the refrigerator and good for up to 1 month at room temperature. The label gives an infusion rate that delivers a 60 mg per kilogram dose in about 15 minutes. Drug page.

Aralast NP (Takeda)

Approved in 2002. A freeze-dried powder in 0.5 g and 1 g vials that is mixed before use and given within 3 hours of mixing. Stored at room temperature up to 25 C.

Zemaira (CSL Behring)

Approved in 2003. A freeze-dried powder in 1,000, 4,000 and 5,000 mg vials, stored up to 25 C; the label gives an infusion time of about 15 minutes for a 60 mg per kilogram dose.

Glassia (Takeda, licensed from Kamada)

Approved in 2010. A ready-to-use liquid given through an in-line filter. Its label is the only one of the 4 that explicitly allows self-administration by the patient or a caregiver at home after training.

Every one of the 4 labels says, in slightly different words, that the effect of augmentation on lung flare-ups and on the progression of emphysema has not been demonstrated in randomized, controlled clinical trials. The products were approved because they raise AAT blood levels, not because a study proved they protect the lungs. Whether they do is the obvious question for anyone facing a lifetime of weekly infusions, and the next section covers the 2 finished studies that tested it.

The best evidence comes from a study called RAPID, which enrolled patients from 2006 to 2010 and was published in The Lancet in 2015. It is not a current trial and it did not test a new drug. It tested the existing treatment: 180 adults with severe AATD at 28 hospitals in 13 countries were randomly given either weekly Zemaira or a dummy infusion (placebo) for 2 years, without anyone knowing which, and CT scans tracked how fast their lungs lost tissue to emphysema (Chapman et al., Lancet 2015). A smaller, earlier study of the same kind, EXACTLE (77 patients, published in 2009), had found a trend in the same direction.

RAPID measured lung loss 2 ways: with the lungs full after a deep breath, and at the end of a normal breath out. With the lungs full, the treated group lost about a third less lung tissue per year than the placebo group, a difference unlikely to be chance (p=0.03). Measured at the end of a normal breath, and with both measurements combined, the treated group again did better, but by a smaller margin that could have been chance (p=0.18 and p=0.06).

What that means for a patient: weekly augmentation probably slows emphysema, and every measure in RAPID pointed that way, but the study did not settle it, and the FDA labels still say a lung benefit has not been demonstrated. That is why augmentation remains standard care for many people with severe AATD and emphysema, and why several companies are working on lung treatments that raise AAT levels with fewer than 52 infusions a year.

AATD Blood Levels Compared, From Untreated to Augmentation to the BEAM-302 Gene Edit

The number doctors track is serum AAT in micromolar. The historical target is 11 micromolar: the FDA labels for augmentation say emphysema risk is increased below it, while noting that keeping levels above it has been proposed as protective but not proven. Beam reports its gene-editing results against it. The chart puts the key figures on one scale. They come from different studies and moments (a trough just before the next weekly dose versus a steady state after a one-time edit), so read them as orders of magnitude, not a head-to-head comparison.

A Year of Each AATD Treatment, Drawn to Scale

AATD Liver Disease Is a Different Problem, and Augmentation Does Not Treat It

That gap is what fazirsiran is aimed at. It is an RNA interference drug from Takeda and Arrowhead that shuts down the liver's production of the misfolded Z-AAT, so less of it accumulates. Its lead Phase 3 trial, REDWOOD (NCT05677971), is recruiting about 160 adults with AATD liver fibrosis and measures whether liver scarring improves on biopsy after about 2 years; ClinicalTrials.gov lists primary completion in January 2029. Gene-editing approaches such as BEAM-302 aim to fix both problems at once, by making normal AAT and less Z-AAT.

AATD Clinical Trials Enrolling Now, and New Treatments in Development

The studies above tested the treatment people already get. The trials in this section test new ones, and several are enrolling patients now. Statuses are from ClinicalTrials.gov, checked September 27, 2026; they change, so confirm on the AATD trials page or the near-you page before contacting a site.

AATD trials enrolling now

Fazirsiran (Takeda), for AATD liver disease

Enrolling, Phase 3, with US sites. An injected RNA drug that cuts the liver's production of misfolded Z-AAT. Takeda runs 2 Phase 3 trials: REDWOOD (NCT05677971), in about 160 adults with liver fibrosis, and a second study (NCT06165341). Drug page.

BEAM-302 (Beam Therapeutics), one-time gene edit

Enrolling, Phase 1/2, with US sites (NCT06389877). A single infusion that corrects the Z mutation in the liver. By August 17, 2026, 38 patients had been dosed; at 60 mg, 93% of circulating AAT was the corrected normal form and Z-AAT fell 84%. Infusion reactions occurred in 41%, all mild to moderate (Beam, September 2026). Drug page.

TSRA-196 (Tessera Therapeutics), gene writing

Enrolling, Phase 1/2, with US sites (NCT07227207), for adults with PiZZ AATD. Recruiting began in April 2026.

AAV gene therapy (Weill Cornell Medicine)

Enrolling, Phase 1, with a US site (NCT06996756). An academic study of an AAV-delivered AAT gene (AAV8hAAT).

KB408 (Krystal Biotech), inhaled

Enrolling, Phase 1, with US sites (NCT06049082). Given by nebulizer rather than infusion.

Alpha-1 15% (Grifols), a more concentrated augmentation

Enrolling, Phase 3, with US sites (NCT07555483). Compares a more concentrated liquid form of Grifols' plasma-derived AAT with the current liquid product.

AIR-001 (AIRNA)

Enrolling, Phase 1, with sites outside the United States (NCT07431112).

In development but not enrolling new patients

Efdoralprin alfa (SAR447537, formerly INBRX-101), Sanofi

A lab-made AAT fused to an antibody fragment and dosed every 3 or 4 weeks. The Phase 2 ElevAATe trial met all primary and key secondary endpoints (Sanofi, October 2025), and its extension study is no longer enrolling. No Phase 3 trial is registered yet. It has FDA fast track and orphan drug designation. Drug page.

WVE-006, Wave Life Sciences

An RNA-editing drug designed to correct the Z-AAT message. Its Phase 1b/2a trial (NCT06405633) is active but no longer recruiting.

Alvelestat, Mereo BioPharma

An oral pill that blocks neutrophil elastase directly instead of replacing AAT. Its Phase 2 trials are complete, and no Phase 3 trial is registered yet. Drug page.

Several programs have stopped: Kamada's inhaled AAT (Phase 3 ended for futility in December 2025), Vertex's VX-814 (Phase 2 terminated) and a later VX-864 study (terminated), Dicerna's belcesiran (Phase 2 terminated; Dicerna is now part of Novo Nordisk), Korro Bio's KRRO-110 (terminated) and Intellia's NTLA-3001 trial (withdrawn before enrolling).

Paying for Alpha-1 Augmentation Therapy

Augmentation is a lifelong weekly infusion of a plasma-derived biologic, so cost and coverage are constant concerns. Each manufacturer runs a support program: PROLASTIN DIRECT (Grifols), Takeda Patient Support for Aralast NP and Glassia, and ZEMAIRA Connect (CSL Behring), with copay help for commercially insured patients on Prolastin-C, Aralast NP and Glassia. NORD's RareCare program has an AATD premium and copay fund, open as of September 2026. The patient assistance finder lists them with the date each was checked and filters by insurance type. Because augmentation is an infusion, how Medicare covers it depends on where and how it is given, which matters when choosing a plan; our Medicare open enrollment checklist explains the difference, and the appeal guide covers what to do if coverage is denied.