No infection risk with alvelestat in patients with AATD in two phase 2 trials.

<bold>Background:</bold> Alvelestat a potent, reversible, selective, oral inhibitor of neutrophil elastase (NE) has been studied in two Phase 2 studies of AATD-(alpha-1 antitrypsin deficiency). The effect of NE suppression on host defence was monitored by reporting of infection requiring antimicrobial therapy as an adverse event of special interest (AESI). <bold>Objectives:</bold> To analyse the effects on NE suppression on frequency of AESIs of infection in AATD patients receiving alvelestat compared to placebo. <bold>Methods:</bold> Two multicentre, double-blind, randomised, placebo-controlled trials completed. Two dose regimes of alvelestat, 120 mg bid and 240 mg bid were tested against placebo in ASTRAEUS and one dose regime of alvelestat 120 mg bid was tested against placebo in ATALANTa. Both studies dosed for 12 weeks. <bold>Results:</bold> 161 Patients across both studies. AESIs of infection demonstrated similar frequency in the alvelestat groups and placebo with no difference in severity. <bold>Conclusions:</bold> Consistent with studies in COPD, bronchiectasis and cystic fibrosis, selective inhibition of NE in patients with AATD with alvelestat was not associated with increased frequency or severity of infection over the course of 12 weeks, including at the 240 mg bid proposed clinical dose. <table-wrap><object-id>erj;64/suppl_68/PA1776/TB1</object-id><object-id>T1</object-id><object-id>TB1</object-id><table><colgroup><col></col><col></col><col></col><col></col><col></col></colgroup><tbody><tr><td><bold>AESI</bold></td><td> <bold>ATALANTA</bold> <bold>Alvelestat 120 mg bid</bold> <bold>(N = 32)</bold> <bold>n (%)</bold> </td><td> <bold>ASTRAEUS</bold> <bold>Alvelestat</bold> <bold>120 mg bid (N = 22)</bold> <bold>n (%)</bold> </td><td> <bold>ASTRAEUS</bold> <bold>Alvelestat</bold> <bold>240 mg bid (N = 40)</bold> <bold>n (%)</bold> </td><td> <bold>Placebo</bold> <bold>(N = 67)</bold> <bold>n (%)</bold> </td></tr><tr><td>Infections</td><td>5 (15.6)</td><td>5 (22.7)</td><td>9 (22.5)</td><td>18 (26.9)</td></tr></tbody></table></table-wrap>