Fazirsiran
An investigational treatment for Alpha-1 Antitrypsin Deficiency.
The same compound appears under different names depending on the context. Here is how to identify Fazirsiran wherever you encounter it, plus the key facts at a glance.
- Generic name
- Fazirsiran
- Development codes
- ARO-AAT, TAK-999
- Drug class
- siRNA (small interfering RNA)
- Manufacturer
- Takeda / Arrowhead
- How it's taken
- In its Phase 3 trials, fazirsiran 200 mg is given as an injection under the skin on day 1 and at week 4, then every 12 weeks.
An investigational injection given under the skin that uses RNA interference to stop the liver from making the misfolded Z-AAT protein that builds up and causes liver damage.
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How Fazirsiran works
Fazirsiran breaks down the messenger RNA that liver cells use to make alpha-1 antitrypsin, so they make far less of the misfolded Z-AAT protein that gets stuck inside them[1]. In trials, the Z-AAT already stored in the liver also went down over time, which suggests the liver can clear it once new production slows.
Mechanism: RNA interference therapy that reduces mutant AAT protein production in liver
Side effects and safety
In the placebo-controlled Phase 2 SEQUOIA trial of 40 adults, no side effects led anyone to stop treatment, and lung function tests stayed stable[1].
In an earlier open-label Phase 2 study of 16 adults, no one stopped treatment because of a side effect. Researchers reported 4 serious adverse events (viral myocarditis, diverticulitis, shortness of breath and vestibular neuronitis, an inflammation of the inner-ear nerve), and all resolved[2].
Because fazirsiran also lowers the Z-AAT circulating in the blood, which is most of the little AAT people with the ZZ type have, researchers track lung function. The 2 Phase 3 trials are still collecting safety data.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Fazirsiran
In its Phase 3 trials, fazirsiran 200 mg is given as an injection under the skin on day 1 and at week 4, then every 12 weeks[3]. It is investigational and only available through clinical trials.
Clinical trial results
In the placebo-controlled Phase 2 SEQUOIA trial of 40 adults, serum Z-AAT fell by 61%, 83% and 94% at week 16 with the 25, 100 and 200 mg doses. In patients who had a follow-up liver biopsy, liver Z-AAT fell by a median of 93%, compared with a 26% increase on placebo[1]. An earlier open-label study of 16 adults reported an 83% median drop in liver Z-AAT, with fibrosis improving in 7 of 15 patients and worsening in 2[2].
Takeda is running 2 placebo-controlled Phase 3 trials: REDWOOD (NCT05677971), in about 160 adults with moderate to advanced liver scarring (METAVIR stage F2 to F4), with primary completion listed for January 2029, and NCT06165341, in about 50 adults with early scarring (stage F1)[3].
Main registered trial: NCT05677971 on ClinicalTrials.gov. Check it for the current status, sites and contacts before asking about enrollment.
Development history
Fazirsiran (formerly ARO-AAT and TAK-999) was developed by Arrowhead Pharmaceuticals. Under an October 2020 agreement, Arrowhead and Takeda co-develop it in the U.S. and would split U.S. profits 50/50 if it is approved, while Takeda leads development and sales elsewhere. Takeda started the Phase 3 REDWOOD trial in March 2023[4].
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Common questions about Fazirsiran
▸What is Fazirsiran?
An investigational injection given under the skin that uses RNA interference to stop the liver from making the misfolded Z-AAT protein that builds up and causes liver damage.
▸How does Fazirsiran work?
Fazirsiran breaks down the messenger RNA that liver cells use to make alpha-1 antitrypsin, so they make far less of the misfolded Z-AAT protein that gets stuck inside them[1]. In trials, the Z-AAT already stored in the liver also went down over time, which suggests the liver can clear it once new production slows.
▸What are the side effects of Fazirsiran?
In the placebo-controlled Phase 2 SEQUOIA trial of 40 adults, no side effects led anyone to stop treatment, and lung function tests stayed stable[1].
In an earlier open-label Phase 2 study of 16 adults, no one stopped treatment because of a side effect. Researchers reported 4 serious adverse events (viral myocarditis, diverticulitis, shortness of breath and vestibular neuronitis, an inflammation of the inner-ear nerve), and all resolved[2].
Because fazirsiran also lowers the Z-AAT circulating in the blood, which is most of the little AAT people with the ZZ type have, researchers track lung function. The 2 Phase 3 trials are still collecting safety data.
▸How is Fazirsiran taken?
In its Phase 3 trials, fazirsiran 200 mg is given as an injection under the skin on day 1 and at week 4, then every 12 weeks[3]. It is investigational and only available through clinical trials.
▸Is Fazirsiran FDA approved?
Fazirsiran is currently in phase 3 clinical trials for Alpha-1 Antitrypsin Deficiency. It has not yet received FDA approval.
▸How does fazirsiran work for Alpha-1 AT deficiency?
Fazirsiran is an RNA interference (RNAi) drug that breaks down the messenger RNA liver cells use to make alpha-1 antitrypsin, so they make much less of the misfolded Z-AAT protein that builds up and damages the liver. It targets the liver disease of AATD, not the lung disease.
▸What is the current development status?
Fazirsiran is in Phase 3. Takeda is running 2 placebo-controlled Phase 3 trials in adults with the PiZZ type and liver scarring, REDWOOD (NCT05677971) and NCT06165341. It is co-developed by Takeda and Arrowhead Pharmaceuticals and is not approved.
▸Does fazirsiran address both liver and lung disease?
No. Fazirsiran targets the liver disease by reducing toxic Z-AAT. It does not raise AAT in the blood; it lowers circulating Z-AAT, so it is not a treatment for AATD lung disease, and people with lung disease may still need augmentation therapy.
▸How is fazirsiran administered?
Fazirsiran is given as an injection under the skin. In its Phase 3 trials, patients get a 200 mg dose on day 1 and at week 4, then every 12 weeks.
▸What are the side effects of fazirsiran?
In the placebo-controlled Phase 2 SEQUOIA trial published in Gastroenterology in 2024, no adverse events led patients to stop fazirsiran and lung function tests stayed stable. Larger Phase 3 trials are still collecting safety data.
▸How does fazirsiran differ from augmentation therapy?
Augmentation therapy replaces the missing AAT protein to protect the lungs, while fazirsiran reduces the toxic misfolded protein accumulating in the liver. They address different aspects of the disease and could potentially be used together.
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Gastroenterology (PubMed 38964420) · 2024-10-01. Fazirsiran for Adults With Alpha-1 Antitrypsin Deficiency Liver Disease: A Phase 2 Placebo Controlled Trial (SEQUOIA). https://pubmed.ncbi.nlm.nih.gov/38964420/
- New England Journal of Medicine (PubMed 35748699) · 2022-08-11. Fazirsiran for Liver Disease Associated with Alpha1-Antitrypsin Deficiency. https://pubmed.ncbi.nlm.nih.gov/35748699/
- ClinicalTrials.gov. Phase 3 study of fazirsiran in AATD-associated liver disease with METAVIR stage F2 to F4 fibrosis (REDWOOD). https://clinicaltrials.gov/study/NCT05677971
- Arrowhead Pharmaceuticals · 2026-06-30. Arrowhead Pharmaceuticals Form 10-Q for the quarter ended June 30, 2026. https://ir.arrowheadpharma.com/sec-filings/sec-filing/10-q/0000879407-26-000057
- Arrowhead Pharmaceuticals · 2020-10-08. Takeda and Arrowhead Collaborate to Co-Develop and Co-Commercialize ARO-AAT for Alpha-1 Antitrypsin-Associated Liver Disease. https://www.takeda.com/newsroom/newsreleases/2020/takeda-and-arrowhead-collaborate-to-co-develop-and-co-commercialize-aro-aat-foralpha-1-antitrypsin-associated-liver-disease/