Alvelestat for AATD meets primary endpoints in phase 2 trial

In patients with alpha-1 antitrypsin deficiency associated lung disease (AATD-LD), treatment with the neutrophil elastase inhibitor alvelestat resulted in a reduction in blood neutrophil elastase activity, Aα-Val360, and desmosine, which were the 3 primary endpoints of the phase 2 ASTRAEUS study. 

“Alvelestat is an oral, selective neutrophil elastase inhibitor, which may have some advantages over plasma-derived AAT, the current standard-of-care for patients with AATD-LD,” mentioned Prof. Robert Stockley (University Hospital Birmingham, UK) at the start of his presentation. “It results in effective lung penetration and is resistant to oxidative inactivation,” he clarified. The phase 2 ASTRAEUS study (NCT03636347) aimed to evaluate the effect of alvelestat on biomarkers of AATD-LD over 12 weeks [1]. The included patients were randomised to 1 of 2 doses of alvelestat, 120 mg, twice daily (n=22); 240 mg, twice daily (n=40), or to a placebo (n=36). 

After 12 weeks of treatment, the change from baseline blood neutrophil elastase activity was significantly larger in the experimental groups than in the placebo group, displayed as the percentage change in the least squared means (LSM):  

• Placebo: -18.1% 


• Alvelestat 120 mg: -83.5%; P=0.001 


• Alvelestat 240 mg: -93.3%; P<0.001 

Also, a significant decrease in Aα-Val360 was observed for the 240 mg group compared with placebo: % change from baseline LSM: placebo +11.7%; alvelestat 240 mg -22.7% (P=0.001). Similarly, a significant decrease in desmosine was reported for the 240 mg dose group: placebo +18.1%; alvelestat 240 mg -13.2% (P=0.041). 

1. Stockley RA, et al. Alvelestat, an Oral Neutrophil Elastase Inhibitor in Alpha-1 Antitrypsin Deficiency (AATD): Results of a Phase II Trial. C15, ATS International Conference 2023, 19–24 May, Washington DC, USA.  

 

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Posted on 12 June 202313 June 2023