Dexpramipexole Oral Add-On for Asthma Significantly Improves Lung Function Over Placebo

Dexpramipexole significantly improved lung function compared to placebo as an add-on oral therapy in people with eosinophilic asthma, according to the latest findings from the phase 3 EXHALE-4 study announced by Areteia Therapeutics.1

“More than half of people with asthma have the eosinophilic subtype, yet there remains a profound need for easily administered oral treatment options that can help address their symptoms, which are often severe,” Ian Pavord, MA, DM, Professor of Respiratory Medicine at the University of Oxford, United Kingdom, and member of Areteia’s Scientific Advisory Board, said in a statement.1 “Initial results from the Phase III EXHALE-4 study are extremely promising, particularly the statistically significant improvement in lung function and the reduction in eosinophils observed with dexpramipexole versus placebo, which show the potential for dexpramipexole to become the first oral treatment approved for eosinophilic asthma.”

EXHALE-4 is a randomized, double-blind, placebo-controlled Phase 3 study evaluating dexpramipexole, an investigational oral small molecule. It is formulated as dexpramipexole dihydrochloride and 75 mg and 150 mg dexpramipexole dihydrochloride are equivalent to 56 mg and 112 mg dexpramipexole, respectively (doses mentioned refer to dexpramipexole dihydrochloride).

The therapy is proposed to inhibit the maturation of eosinophils in the bone marrow, based on evidence from cell cultures and human biopsies, thereby lowering peripheral blood and tissue eosinophil levels.

The study is evaluating dexpramipexole in 600 participants aged ≥12 years with inadequately controlled moderate-to-severe asthma and blood Absolute Eosinophil Count ≥300 cells/μL. They continued their usual asthma medications and were randomized to add either dexpramipexole (150 mg or 75 mg) or placebo in a 5:5:1 ratio, respectively. Participants were randomly assigned to placebo BID, 150 mg BID, or 75 mg BID dexpramipexole groups in a 5:5:1 ratio respectively.

The study is primarily evaluating the absolute change from baseline in pre-bronchodilator forced expiratory volume (pre-BD FEV1) averaged over Weeks 20 and 24 between 150 mg twice daily (BID) dexpramipexole dose and placebo. Dexpramipexole 75mg BID was included to assess eosinophil lowering effects in blood and pharmacokinetic/pharmacodynamic relationship.

Investigators found that dexpramipexole significantly improved lung function and met the study’s primary endpoint, with a statistically significant improvement in pre-BD FEV1in the dexpramipexole 150 mg BID group compared with placebo. Significant improvements in lung function were observed as early as Week 4. Dexpramipexole 150 mg BID and 75mg BID also significantly reduced blood AEC averaged over Weeks 20 and 24 compared with placebo. The therapy was well tolerated, with a safety profile similar to previous studies. More detailed data will be presented at an upcoming medical meeting.

“We are pleased to report positive topline results for the EXHALE-4 Phase III study, which demonstrate dexpramipexole’s ability to address the unmet needs of people with eosinophilic asthma by improving their lung function. Dexpramipexole has the potential to be the first oral treatment for this indication,” Jorge Bartolome, President and Chief Executive Officer of Areteia, added.1 “We look forward to presenting the full EXHALE-4 results at an upcoming medical meeting as we also advance the EXHALE-2 and EXHALE-3 studies and work to transform the patient journey in eosinophilic asthma.”

Dexpramipexole previously demonstrated in a significant, dose-dependent reduction in blood AEC at all doses tested (37.5 mg, 75 mg, or 150 mg BID) compared with placebo in a Phase II study in participants with moderate-to-severe eosinophilic asthma with dose-dependent improvements in lung function and a well-tolerated safety profile in other EXHALE studies.2

References

1. Areteia Therapeutics Announces Positive Topline Results from the First Phase III Study of Oral Dexpramipexole in Eosinophilic Asthma. News release. September 16, 2025. News release. Areteia Therapeutics. https://www.businesswire.com/news/home/20250916566261/en/Areteia-Therapeutics-Announces-Positive-Topline-Results-from-the-First-Phase-III-Study-of-Oral-Dexpramipexole-in-Eosinophilic-Asthma

2. Siddiqui S, Wenzel SE, Bozik ME, et al. Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial. J Allergy Clin Immunol. 2023;152(5):1121-1130.e10. doi:10.1016/j.jaci.2023.05.014