Positive Trial Results Released for Alpha-1 Antitrypsin Deficiency-Associated Emphysema Treatment

Mereo BioPharma Group has just announced positive results from their Phase 2 study called ASTRAEUS. This study investigated alvelestat (MPH-966), which is an oral neutrophil elastase inhibitor, as a treatment for alpha-1 antitrypsin deficiency (AATD) patients who have emphysema.


AATD-LD stands for AATD-related lung diseases.

AATD is a condition which is genetic in nature. It causes progressive alveolar destruction which can lead to emphysema. Patients have low levels of a protein called AAT which is responsible for inhibiting neutrophil elastase.

Initial symptoms of AATD-LD, which most frequently presents when patients are between 20-50, are cough, shortness of breath, and a reduced ability to tolerate exercise,

Patients with severe AATD-LD may need chronic oxygen therapy, surgery, or a lung transplant. The condition can be fatal.

Alvelestat is an oral therapy which inhibits neutrophil elastase. This is a primary enzyme which destroys lung tissue. It has been investigated in many lung diseases such as cystic fibrosis (CF), bronchiectasis, and COPD, and demonstrated efficacy.


The ASTRAEUS trial was a Phase 2, double-blind investigation which included 99 patients who had severe AATD related emphysema. The trial was conducted across 26 locations in the United States, UK, and EU. In total, 98 patients were dosed. Patients were randomized to receive either a high dose of alvelestat, a low dose, or placebo. 41 patients were in the high dose group, 22 were in the low dose group, and 36 were in the placebo group. All patients were dosed for 12 weeks and then had a 4 week follow-up.

There were three primary biomarkers in this trial. These were the percent change from baseline in the treatment group compared to the placebo for blood neutrophil elastase activity, desmosine levels, and a Aα-Val360 levels. Secondary endpoints were safety, tolerability, PK, and the proportion of participants lower than the limit of quantitation. There were also exploratory endpoints in this trial with included biomarkers of lung damage, inflammatory biomarkers, pulmonary function tests, rate of exacerbations of COPD, and St. George’s Respiratory Questionnaire.

The results demonstrated that the high dose of the treatment provided statistically significant improvements compared to the placebo for all three biomarkers. The researchers are extremely optimistic about these results not only for AATD but for other lung conditions.

Most of the AEs documented in this trial were mild or moderate.

In the second half of this year, the company plans to examine other studies to better asses the secondary and the exploratory endpoints. They will next meet with regulators in Europe and the US to design a registration trial for the treatment.

You can read more about this trial here.

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