Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2)

Mario Castro; Edward Kerwin; David Miller; Andrew Pedinoff; Lawrence Sher; Pamela Cardenas; Barbara Knorr; David Lawrence; Diego Ossa; Wei Wang; Jorge F Maspero

doi:10.1016/j.eclinm.2021.100847

Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2)

EClinicalMedicine. 2021 Apr 25:35:100847. doi: 10.1016/j.eclinm.2021.100847. eCollection 2021 May.

Authors

Mario Castro¹, Edward Kerwin², David Miller³, Andrew Pedinoff⁴, Lawrence Sher⁵, Pamela Cardenas⁶, Barbara Knorr⁶, David Lawrence⁷, Diego Ossa⁷, Wei Wang⁸, Jorge F Maspero⁹

Affiliations

¹ Division of Pulmonary, Critical Care Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
² Clinical Research Institute of Southern Oregon, Medford, OR, USA.
³ Northeast Medical Research Associates, Inc., North Dartmouth, MA, USA.
⁴ Princeton Allergy & Asthma Associates, Skillman, NJ, USA.
⁵ Peninsula Research Associates, Rolling Hills Estates, CA, USA.
⁶ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
⁷ Novartis Pharma AG, Basel, Switzerland.
⁸ Novartis Institutes for Biomedical Research Co., Ltd, Shanghai, China.
⁹ Allergy and Respiratory Research Unit, Fundación CIDEA, Buenos Aires, Argentina.

Abstract

Background: These studies assessed the efficacy and safety of fevipiprant, an oral antagonist of the prostaglandin D₂ (PGD₂) receptor (DP₂), compared with placebo when added to standard-of-care (SoC) asthma therapy in patients with uncontrolled asthma.

Methods: ZEAL-1 (NCT03215758) and ZEAL-2 (NCT03226392) are two replicate, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies in which fevipiprant 150 mg once daily (o.d.) or placebo was added to SoC asthma therapy in patients aged ≥12 years with uncontrolled asthma. Primary endpoint: change from baseline in pre-dose forced expiratory volume in 1 s (FEV₁) after 12 weeks' treatment. Key secondary endpoints: daytime asthma symptom score, short-acting β-agonist (SABA) use and Asthma Quality-of-Life Questionnaire (AQLQ+12) score after 12-weeks treatment.

Findings: 662 patients in ZEAL-1 and 685 patients in ZEAL-2 completed the treatment period. In ZEAL-1, the least squares (LS) mean change from baseline in pre-dose FEV₁ was 112 mL in fevipiprant vs 71 mL in placebo group (difference [∆]:41 mL; 95% CI: -6, 88; adjusted p-value 0·088). In ZEAL-2, the LS mean change in pre-dose FEV₁ was 126 mL and 157 mL in the fevipiprant and placebo groups, respectively (∆:-31 mL; 95% CI: -80, 18; adjusted p-value 0·214). For both studies, there were no statistically significant differences in the key secondary objectives between the treatment groups.

Interpretation: The ZEAL studies did not demonstrate significant improvement in lung function or other clinical outcomes. These results suggest that DP₂ receptor inhibition with fevipiprant is not effective in the studied patient population.