RT Journal Article
SR Electronic
T1 QAW039 (fevipiprant) improves lung function and control of asthma symptoms in patients with more severe air flow limitation: A proof-of-concept study
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2125
DO 10.1183/13993003.congress-2015.PA2125
VO 46
IS suppl 59
A1 Veit J. Erpenbeck
A1 Todor A. Popov
A1 S. David Miller
A1 Steven F. Weinstein
A1 Sheldon Spector
A1 Baldur Magnusson
A1 Wande Osuntokun
A1 Paul Goldsmith
A1 Markus Weiss
A1 Jutta Beier
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/PA2125.abstract
AB Aim: To collect clinical and pharmacokinetic (PK) data for QAW039 (fevipiprant), a novel oral CRTh2 receptor antagonist, for asthma treatment.Methods: We assessed efficacy (change in trough FEV1 from baseline to day 29), ACQ scores, PK of QAW039 and safety vs placebo (PBO). Atopic patients (pts) with mild-to-moderate persistent asthma (ACQ scores ≥1.5) and predicted FEV1 between 60-85% at baseline were randomised to QAW039 500mg or PBO once-daily for 28 days after a run-in period of up to 28 days where ICS or combinations ICS and LABAs were withdrawn.Results: A total of 170 pts were randomised to QAW039 (n=82) and PBO (n=88). There were no significant differences between QAW039 and PBO groups for trough FEV1 or ACQ in the whole population. Amongst the various subgroup analyses conducted, positive results were seen in the subgroup of pts (QAW039, n=28; PBO, n=37) with airflow limitation of <70% of predicted at baseline FEV1 with significant improvement for both FEV1 (Δ[QAW-PBO]=+207mL; 90%CI: 96, 319; p=0.002) and ACQ7 (Δ[QAW-PBO]=-0.41; 90%CI: -0.69, -0.13; p=0. 009). QAW039 (n=82) reached a mean maximum concentration (Cmax) of 3440ng/mL on day 28 at a median Tmax of 1h (range 0.5–4h). The AUCtau ratio (day 28 AUC0-24h–day 1 AUC0-24h) of 1.2 indicated modest accumulation of QAW039 upon repeat dosing. Most AEs were mild/moderate and balanced between both groups with no SAEs.Conclusion: QAW039 may improve lung function and asthma control in pts with greater severity of airflow limitation and had a favourable safety profile in all treated pts. Positive results were seen in a post-hoc subgroup analysis and are thus interpreted with caution.