Mereo BioPharma released positive results from its phase 2 clinical trial of alvelestat, an investigational oral neutrophil elastase (NE) inhibitor being developed to treat patients with severe alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD).

“These positive top-line results demonstrate the clear impact of alvelestat on key known biomarkers along the pathogenic pathway of AATD-LD,” Denise Scots-Knight, PhD, chief executive officer of Mereo, said in a news release. “Alvelestat has the potential to be the first-in-class oral neutrophil elastase inhibitor for the treatment of AATD-LD.”

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The double-blind, placebo-controlled trial, called ASTRAEUS, included 99 patients with severe AATD-LD from North America and Europe. It assessed high and low doses of alvelestat vs placebo over a 12-week study period, and at weeks 4, 8, and 12, 3 primary endpoints were evaluated: blood NE activity, Aα-val360, and desmosine, which is the breakdown product of elastin. Secondary endpoints included pharmacokinetics, safety, tolerability, and the percentage of patients with NE below the limit of quantitation.

The results revealed that the high dose of alvelestat led to significant changes in all 3 biomarkers, demonstrating specific inhibition of NE in patients with severe AATD-related emphysema.

The company expects to build on its success by developing a broader patient group for further investigations, in particular among patients already on alpha-1 antitrypsin augmentation therapy. In the current trial, only 11% of patients had already received augmentation therapy, and the washout period for those patients was more than 2 years.

“We look forward to analyzing the additional data on the secondary and exploratory endpoints and to engaging with the regulators on the design of a pivotal study,” Dr. Scots-Knight said.


Mereo BioPharma announces positive top-line efficacy and safety data from “ASTRAEUS” phase 2 trial of alvelestat in alpha-1 antitrypsin deficiency-associated emphysema. News Release. Mereo BioPharma; May 9, 2022.