The Food and Drug Administration (FDA) has granted Fast Track designation to alvelestat (MPH-966) for the treatment of patients with alpha-1 antitrypsin deficiency (AATD)-associated lung disease.

AATD is a rare, genetic disease caused by mutations in the SERPINA1 gene. The genetic changes result in a deficiency of alpha-1 antitrypsin, a protein produced in the liver that helps protect the lungs from damaging enzymes, specifically neutrophil elastase. The disease begins in early adult life and can lead to pulmonary emphysema.

Alvelestat is an investigational oral neutrophil elastase inhibitor designed to protect AATD patients from further lung damage. The designation is supported by positive topline data from the 12-week phase 2 ASTRAEUS study (ClinicalTrials.gov Identifier: NCT03636347) which compared the mechanistic effect, safety and tolerability of alvelestat (high or low dose) to placebo in patients with severe AATD-associated emphysema. 

Findings showed that treatment with alvelestat high dose achieved statistically significant changes in all 3 primary biomarker endpoints related to AATD-associated lung disease (blood neutrophil elastase activity, blood Aα-Val 360 levels, plasma desmosine/isodesmosine levels). 

The Company expects to provide additional updates on the ASTRAEUS study on October 31, 2022. Additionally, the Company is currently evaluating alvelestat in the phase 2 ATALANTa trial (ClinicalTrials.gov Identifier: NCT03679598) in a broader range of AATD patient populations.

“AATD is a devastating inherited condition which severely affects patients’ quality of life. In the ASTRAEUS study, we demonstrated alvelestat’s ability to inhibit multiple specific biomarkers relevant to the disease pathway based on neutrophil elastase inhibition,” said Dr Denise Scots-Knight, CEO of Mereo. “We are grateful to the FDA for granting us Fast Track designation, and for their recognition of alvelestat as a potentially first-in-class oral neutrophil elastase inhibitor. We look forward to the R&D update on the alvelestat program this month, and to our future interactions with the FDA to review our plans for a pivotal trial.”

References

  1. Mereo BioPharma receives FDA Fast Track designation for alvelestat for treatment of alpha-1 antitrypsin deficiency (AATD)-associated lung disease. News release. Mereo BioPharma Group plc. October 17, 2022. Accessed October 18, 2022. https://www.globenewswire.com/news-release/2022/10/17/2535304/0/en/Mereo-BioPharma-Receives-FDA-Fast-Track-Designation-for-Alvelestat-for-Treatment-of-Alpha-1-Antitrypsin-Deficiency-AATD-associated-Lung-Disease.html
  2. 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 Group plc. May 9, 2022. Accessed October 18, 2022. https://www.mereobiopharma.com/news-and-events/news/2022/may/mereo-biopharma-announces-positive-top-line-efficacy-and-safety-data-from-astraeus-phase-2-trial-of-alvelestat-in-alpha-1-antitrypsin-deficiency-associated-emphysema/