Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial.

Abstract

BACKGROUND:

There is a need for new and effective oral asthma therapies. Dexpramipexole, an oral eosinophil-lowering drug, has not previously been studied in asthma.

OBJECTIVE:

We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma.

METHODS:

We performed a randomized, double-blind, placebo-controlled proof-of-concept trial in adults with inadequately controlled moderate to severe asthma and blood absolute eosinophil count (AEC) greater than or equal to 300/μL. Subjects were randomly assigned (1:1:1:1) to dexpramipexole 37.5, 75, or 150 mg BID (twice-daily) or placebo. The primary end point was the relative change in AEC from baseline to week 12. Prebronchodilator FEV1 week-12 change from baseline was a key secondary end point. Nasal eosinophil peroxidase was an exploratory end point.

RESULTS:

A total of 103 subjects were randomly assigned to dexpramipexole 37.5 mg BID (N = 22), 75 mg BID (N = 26), 150 mg BID (N = 28), or placebo (N = 27). Dexpramipexole significantly reduced placebo-corrected AEC week-12 ratio to baseline, in both the 150-mg BID (ratio, 0.23; 95% CI, 0.12-0.43; P < .0001) and the 75-mg BID (ratio, 0.34; 95% CI, 0.18-0.65; P = .0014) dose groups, corresponding to 77% and 66% reductions, respectively. Dexpramipexole reduced the exploratory end point of nasal eosinophil peroxidase week-12 ratio to baseline in the 150-mg BID (median, 0.11; P = .020) and the 75-mg BID (median, 0.17; P = .021) groups. Placebo-corrected FEV1 increases were observed starting at week 4 (nonsignificant). Dexpramipexole displayed a favorable safety profile.

CONCLUSIONS:

Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the clinical efficacy of dexpramipexole in asthma.

• Authors: Salman Siddiqui, Sally E Wenzel, Michael E Bozik, Donald G Archibald, Steven I Dworetzky, James L Mather, Randall Killingsworth, Natasha Ghearing, Justin T Schwartz, Sergei I Ochkur, Elizabeth A Jacobsen, William W Busse, Reynold A Panettieri, Calman Prussin
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 152 Issue 5 Pg. 1121-1130.e10 (11 2023) ISSN: 1097-6825 [Electronic] United States
• PMID: 37277072 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Pramipexole
• Eosinophil Peroxidase
• Anti-Asthmatic Agents

Topics

• Adult
• Humans
• Pramipexole (pharmacology, therapeutic use)
• Eosinophil Peroxidase
• Asthma (drug therapy)
• Pulmonary Eosinophilia (drug therapy)
• Eosinophils
• Treatment Outcome
• Double-Blind Method
• Anti-Asthmatic Agents (therapeutic use)