title: The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma.
abstract: There is an unmet medical need for allergic asthma patients who are uncontrolled on conventional therapies. The aim of this study was to collect efficacy and safety data for QAW039, an oral chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist, for the treatment of asthma.
  
  
  
  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 inhaled corticosteroids (ICS) and long-acting β-agonists (LABA) and randomized (1:1) to QAW039 (500 mg once daily) or to placebo for 28 days.
  
  
  
  Overall, 157 patients completed the study. There were no significant differences between QAW039 and placebo for trough forced expiratory volume in 1 s (FEV1) or Asthma control questionnaire (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 (QAW039- Placebo [Δ] = 207 mL; 90% confidence interval [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 h (range 0.5-4 h). Most adverse events (AEs) were mild/moderate and balanced between both groups, with no serious AEs.
  
  
  
  In the general study population, no improvement in lung function was observed with QAW039. However, a subgroup 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.
  
  
  
  ClinicalTrials.govNCT01253603.
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. Electronic address: veit.erpenbeck@novartis.com.
authors.forename: Veit J
authors.initials: VJ
authors.lastname: Erpenbeck
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria. Electronic address: ted.popov@gmail.com.
authors.forename: Todor A
authors.initials: TA
authors.lastname: Popov
authors.affiliation: NEMRA, North Dartmouth, MA, United States. Electronic address: dmiller@nemra-us.com.
authors.forename: David
authors.initials: D
authors.lastname: Miller
authors.affiliation: Allergy & Immunology, Allergy and Asthma Specialists Medical Group and Research Center, CA, United States. Electronic address: sfw@ocallergy.com.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Weinstein
authors.affiliation: Allergy & Asthma, California Allergy and Asthma Medical Group Inc, CA, United States. Electronic address: calallergy@gmail.com.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Spector
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. Electronic address: baldur.magnusson@novartis.com.
authors.forename: Baldur
authors.initials: B
authors.lastname: Magnusson
authors.affiliation: Novartis Pharmaceuticals, Horsham, United Kingdom. Electronic address: wande.osuntokun@takeda.com.
authors.forename: Wande
authors.initials: W
authors.lastname: Osuntokun
authors.affiliation: Novartis Pharmaceuticals, Horsham, United Kingdom. Electronic address: pgoldsmith0@gmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Goldsmith
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. Electronic address: markus.weiss@novartis.com.
authors.forename: Markus
authors.initials: M
authors.lastname: Weiss
authors.affiliation: INSAF, Respiratory Research Institute GmbH, Wiesbaden, Germany. Electronic address: j.beier@insaf-wi.de.
authors.forename: Jutta
authors.initials: J
authors.lastname: Beier
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007210:Indoleacetic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D007210:Indoleacetic Acids; D011725:Pyridines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C000604875:fevipiprant; C036293:prostaglandin D2 receptor
keywords: Asthma; Chemoattractant receptor-homologous molecule expressed on Th2 cells; Clinical trial