QAW039 (fevipiprant) improves lung function and control of asthma symptoms in patients with more severe air flow limitation: A proof-of-concept study

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 FEV 1 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 FEV 1 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or PBO once-daily for 28 days after a run-in period of up to 28 days where ICS or combinations ICS and LABAs were withdrawn.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 FEV 1 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 1 with significant improvement for both FEV 1 (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 (C max ) of 3440ng/mL on day 28 at a median T max of 1h (range 0.5–4h). The AUC tau ratio (day 28 AUC 0-24h –day 1 AUC 0-24h ) 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.