Alvelestat
An investigational treatment for Alpha-1 Antitrypsin Deficiency.
The same compound appears under different names depending on the context. Here is how to identify Alvelestat wherever you encounter it, plus the key facts at a glance.
- Generic name
- Alvelestat
- Development codes
- MPH966, AZD9668
- Drug class
- Small molecule enzyme inhibitor
- Manufacturer
- Mereo BioPharma
- How it's taken
- Alvelestat is taken by mouth twice a day.
An oral tablet that directly blocks the neutrophil elastase enzyme from destroying lung tissue. Instead of replacing the missing AAT protein, it blocks the damage at the source.
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How Alvelestat works
Alvelestat blocks an enzyme called neutrophil elastase that damages lung tissue in alpha-1 antitrypsin deficiency. In this disease, there's an imbalance between this damaging enzyme and the body's natural protection. Alvelestat tips the balance back by reducing elastase activity, protecting the lungs from further damage.
Mechanism: Neutrophil elastase inhibitor protecting lung tissue
Side effects and safety
In 2 placebo-controlled Phase 2 trials of 161 adults, the most common side effect was headache, especially at the higher 240 mg dose, followed by nausea (usually with the headache) and dizziness. Headache led 8 people to stop (1 on 120 mg and 7 on 240 mg); in those who kept taking it, headaches became about as common as on placebo[1].
In the ASTRAEUS trial, 1 person met the stopping rule for raised liver enzymes and 1 for a heart-rhythm (QTc) change, both on 240 mg, and both resolved. There were 6 serious adverse events in 4 people, and all resolved. The researchers reported no safety signals of concern[1].
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 Alvelestat
Alvelestat is taken by mouth twice a day. In Phase 2 trials, only the 240 mg twice-daily dose improved disease-activity markers, and the researchers recommended that dose for further study[1]. It is still in clinical development and not approved.
Clinical trial results
Two 12-week, placebo-controlled Phase 2 trials enrolled 161 adults with severe AATD: ATALANTa (63 people, 120 mg twice daily) and ASTRAEUS (98 people, 120 or 240 mg twice daily). Both doses suppressed neutrophil elastase in the blood, but only 240 mg significantly lowered A-alpha-Val360, a marker of elastase activity, and desmosine, a marker of elastin (lung tissue) breakdown[1]. These trials measured markers, not lung function or emphysema progression.
Main registered trial: NCT03679598 on ClinicalTrials.gov. Check it for the current status, sites and contacts before asking about enrollment.
Development history
Alvelestat was first developed by AstraZeneca as AZD9668 and is now developed by Mereo BioPharma, which also calls it MPH966. It has FDA orphan drug and Fast Track designations for AATD lung disease. In August 2026, Mereo signed an option and license agreement giving Sentynl Therapeutics, a Zydus company, a path to U.S. commercial rights, and said the Phase 3 program could begin in early 2027[2].
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Common questions about Alvelestat
▸What is Alvelestat?
An oral tablet that directly blocks the neutrophil elastase enzyme from destroying lung tissue. Instead of replacing the missing AAT protein, it blocks the damage at the source.
▸How does Alvelestat work?
Alvelestat blocks an enzyme called neutrophil elastase that damages lung tissue in alpha-1 antitrypsin deficiency. In this disease, there's an imbalance between this damaging enzyme and the body's natural protection. Alvelestat tips the balance back by reducing elastase activity, protecting the lungs from further damage.
▸What are the side effects of Alvelestat?
In 2 placebo-controlled Phase 2 trials of 161 adults, the most common side effect was headache, especially at the higher 240 mg dose, followed by nausea (usually with the headache) and dizziness. Headache led 8 people to stop (1 on 120 mg and 7 on 240 mg); in those who kept taking it, headaches became about as common as on placebo[1].
In the ASTRAEUS trial, 1 person met the stopping rule for raised liver enzymes and 1 for a heart-rhythm (QTc) change, both on 240 mg, and both resolved. There were 6 serious adverse events in 4 people, and all resolved. The researchers reported no safety signals of concern[1].
▸How is Alvelestat taken?
Alvelestat is taken by mouth twice a day. In Phase 2 trials, only the 240 mg twice-daily dose improved disease-activity markers, and the researchers recommended that dose for further study[1]. It is still in clinical development and not approved.
▸Is Alvelestat FDA approved?
Alvelestat is currently in phase 2 clinical trials for Alpha-1 Antitrypsin Deficiency. It has not yet received FDA approval.
▸What is alvelestat's mechanism of action?
Alvelestat is a neutrophil elastase inhibitor. In Alpha-1 AT deficiency, the lung lacks sufficient AAT to neutralize neutrophil elastase, an enzyme that destroys lung tissue. Alvelestat directly inhibits this destructive enzyme.
▸What is the current development status?
Alvelestat has completed Phase 2 testing for Alpha-1 AT deficiency-related lung disease. Mereo BioPharma leads development and has said a global Phase 3 trial could begin in early 2027. In August 2026, Mereo gave Sentynl Therapeutics, a Zydus company, an option on U.S. commercial rights.
▸How does alvelestat differ from augmentation therapy?
Augmentation therapy replaces the missing AAT protein, while alvelestat directly blocks neutrophil elastase, the destructive enzyme that AAT normally controls. Both approaches aim to protect the lungs but through different mechanisms.
▸How is alvelestat taken?
Alvelestat is a pill taken by mouth twice a day, which would be a convenience advantage over weekly IV augmentation therapy if approved. The dose carried forward from Phase 2 is 240 mg twice daily.
▸What are the side effects of alvelestat?
In 2 Phase 2 trials of 161 adults published in the European Respiratory Journal in 2025, headache was the most common side effect, especially at 240 mg, followed by nausea and dizziness. Headache led 8 people to stop the drug, and the researchers reported no safety signals of concern.
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.
- European Respiratory Journal (PubMed 40967767) · 2025-12-18. Two randomised controlled phase 2 studies of the oral neutrophil elastase inhibitor alvelestat in alpha-1 antitrypsin deficiency. https://pubmed.ncbi.nlm.nih.gov/40967767/
- Mereo BioPharma · 2026-08-11. Mereo BioPharma and Sentynl Therapeutics Announce Option and License Agreement for alvelestat in AATD-LD. https://www.mereobiopharma.com/news/option-and-license-agreement/