Areteia Therapeutics announced positive topline results from its Phase III EXHALE-4 study of dexpramipexole, an investigational oral therapy for eosinophilic asthma. The drug met its primary endpoint with statistically significant improvement in lung function compared to placebo, marking a potential breakthrough for patients with this challenging asthma subtype.
Study Results and Clinical Impact
In the EXHALE-4 trial, dexpramipexole 150 mg twice daily significantly improved lung function averaged over Weeks 20 and 24, as measured by the change from baseline in pre-bronchodilator forced expiratory volume (pre-BD FEV1) compared with placebo. Notably, significant improvements in lung function were observed as early as Week 4, suggesting rapid therapeutic benefit.
The study also demonstrated that both dexpramipexole 150 mg and 75 mg twice daily significantly reduced blood absolute eosinophil count (AEC) averaged over Weeks 20 and 24, measured by the change from baseline in geometric mean AEC values compared with placebo.
"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," said Ian Pavord, Professor of Respiratory Medicine at the University of Oxford and member of Areteia's Scientific Advisory Board.
Trial Design and Patient Population
EXHALE-4 is a randomized, double-blind, placebo-controlled Phase III study involving 600 participants aged 12 years and older with inadequately controlled moderate-to-severe asthma and blood AEC ≥300 cells/μL. Participants continued their usual asthma medications while adding either dexpramipexole or placebo in a 5:5:1 ratio for placebo, 150 mg twice daily, and 75 mg twice daily groups, respectively.
The primary endpoint focused on pre-BD FEV1 absolute change from baseline, with the primary comparison conducted between the dexpramipexole 150 mg twice daily dose and placebo. The 75 mg twice daily dose was included to assess eosinophil lowering effects and pharmacokinetic/pharmacodynamic relationships.
Mechanism and Market Potential
Dexpramipexole is an oral small molecule that inhibits 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. This mechanism addresses the underlying pathophysiology of eosinophilic asthma, which affects more than half of all asthma patients.
"Dexpramipexole has the potential to be the first oral treatment for this indication," said Jorge Bartolome, President and Chief Executive Officer of Areteia. Currently, injectable anti-IL-5/5R biologic therapies are the only approved treatments that provide clinical benefit through eosinophil lowering, representing a global asthma biologic market valued at approximately $10 billion USD.
Safety Profile and Development Program
In the EXHALE-4 study, dexpramipexole was well tolerated with a safety profile similar to previous studies. The drug's tolerability profile builds on earlier Phase II results where oral dexpramipexole was well tolerated with adverse events balanced across treatment and placebo groups.
Areteia continues to enroll patients in two additional Phase III studies: EXHALE-2 and EXHALE-3, which are 52-week global exacerbation trials designed to evaluate dexpramipexole's impact on asthma exacerbations in eosinophilic asthma patients.
The company plans to present full EXHALE-4 results at an upcoming medical meeting. Dexpramipexole remains an investigational drug and is not licensed for use in eosinophilic asthma.
