Erpenbeck, Veit, Popov, Todor A, Miller, David, Weinstein, Steven F, Spector, Sheldon, Magnusson, Baldur, Osuntokun, Wande, Goldsmith, Paul, Weiss, Markus and Beier, Jutta (2016) The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma. Pulmonary pharmacology & therapeutics, 39. pp. 54-63. ISSN 1522-9629; 1094-5539

Abstract

Abstract
Rationale
There is an unmet medical need for allergic asthma patients who are uncontrolled on conventional therapies.
Objectives
To collect efficacy and safety data for QAW039, an oral CRTh2 receptor antagonist, for the treatment of asthma.
Methods
This was an exploratory phase II, double-blind, randomized, placebo-controlled multi-center study. Patients with mild-to-moderate uncontrolled allergic asthma (N=170) were either without or weaned off ICS and LABA and randomized (1:1) to QAW039A (500 mg once daily) or to placebo for 28 days.
Measurements and Main Results
Overall, 157 patients completed the study. There were no significant differences between QAW039 and placebo for trough FEV1 or ACQ in the total population. Subgroup analyses demonstrated that patients with a FEV1 <70% of predicted at baseline treated with QAW039 had significant improvement compared with placebo in trough FEV1 (QAW- Placebo [Δ]= 207mL; 90%CI: 96, 319; P=0.002) and ACQ7 (Δ= -0.41; 90%CI: -0.69, -0.13; P=0.009). QAW039 reached a mean maximum concentration (Cmax) of 3440 ng/mL on day 28 at a median Tmax of 1 hour (range 0.5–4 hour). Most AEs were mild/moderate and balanced between both groups, with no SAEs.
Conclusion
In the general study population, no improvement in lung function was observed with QAW039. However, an interim analysis revealed that patients with greater severity of airflow limitation (FEV1 < 70%), had improved lung function and asthma control when treated with QAW039. QAW039 also demonstrated a favorable safety profile.

Item Type:	Article
Date Deposited:	19 Oct 2017 00:45
Last Modified:	19 Oct 2017 00:45
URI:	https://oak.novartis.com/id/eprint/26942