Areteia Reports Positive Phase III Results for Oral Dexpramipexole in Eosinophilic Asthma
Areteia Therapeutics, Inc. announced today that its Phase III EXHALE-4 clinical trial has met key efficacy and safety endpoints for dexpramipexole, an investigational oral therapy being developed as an add-on treatment for eosinophilic asthma. These topline results mark a significant milestone in the company’s effort to bring forward a new, more convenient treatment option for patients with this challenging subtype of asthma.
Asthma affects millions worldwide, and more than half of those living with the condition are believed to have the eosinophilic subtype. This form of asthma is characterized by elevated eosinophils, a type of white blood cell that drives airway inflammation. Despite the availability of inhaled corticosteroids and biologic therapies, there remains a critical need for effective, easy-to-administer oral treatments that can help control symptoms and improve lung function.
Commenting on the findings, Professor Ian Pavord, MA, DM, of the University of Oxford and a member of Areteia’s Scientific Advisory Board, highlighted the significance of the results. “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,” he said. “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. These outcomes show the potential for dexpramipexole to become the first oral treatment approved for eosinophilic asthma.”
Jorge Bartolome, President and Chief Executive Officer of Areteia, also emphasized the importance of this milestone for patients. “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,” Bartolome stated. “Dexpramipexole has the potential to be the first oral treatment for this indication. We look forward to presenting the full EXHALE-4 results at an upcoming medical meeting as we continue to advance the EXHALE-2 and EXHALE-3 studies. Our goal is to transform the patient journey in eosinophilic asthma.”
The EXHALE-4 trial evaluated dexpramipexole at two different dose levels. Patients receiving dexpramipexole 150 mg twice daily (BID) demonstrated statistically significant improvements in lung function compared to those receiving placebo, as measured by changes in pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1). Notably, these improvements were observed as early as Week 4 of treatment and were sustained through Weeks 20 and 24.
In addition to lung function, the study also measured reductions in absolute eosinophil counts (AEC), an important biomarker of disease activity in eosinophilic asthma. Both the 150 mg BID and 75 mg BID doses of dexpramipexole achieved statistically significant reductions in blood eosinophil levels compared with placebo. These findings suggest that dexpramipexole not only improves breathing capacity but also addresses the underlying inflammatory process that drives eosinophilic asthma.
Safety results from EXHALE-4 were consistent with earlier clinical trials of dexpramipexole. The drug was generally well tolerated, and no new safety signals were observed. This safety profile further supports its potential as a practical oral therapy that could complement or provide an alternative to injectable biologics currently used in severe cases.
Full results from the EXHALE-4 trial will be presented at an upcoming medical meeting. Areteia also continues to evaluate dexpramipexole in two additional Phase III studies, EXHALE-2 and EXHALE-3, which are expected to provide further insights into the therapy’s efficacy and safety profile across diverse patient populations.
Dexpramipexole remains an investigational medicine and is not yet approved for use in eosinophilic asthma. However, the positive findings from EXHALE-4 represent an important step forward in the company’s mission to expand treatment options and improve outcomes for patients with this difficult-to-treat condition.
About the EXHALE-4 Study (NCT05748600)
EXHALE-4 is a randomized, double-blind, placebo-controlled Phase III study in participants (N=600) aged ≥12 years with inadequately controlled moderate-to-severe asthma and blood AEC ≥300 cells/μL. Participants continued their usual asthma medications and added either dexpramipexole or placebo. Participants were randomly assignedto placebo BID, 150 mg BID, or 75 mg BID dexpramipexole groups in a 5:5:1 ratio respectively. The primary endpoint of the study is pre-BD FEV1, absolute change from baseline, averaged over Weeks 20 and 24. The primary comparison was conducted on the dexpramipexole 150 mg BID dose and placebo. Dexpramipexole 75mg BID was also included to assess eosinophil lowering effects in blood as well as pharmacokinetic/pharmacodynamic relationship.
About Dexpramipexole
Dexpramipexole, an investigational drug, is an oral small molecule that has been shown to lower eosinophil levels in blood and tissue and is currently in Phase III development for treatment of adults with moderate-to-severe eosinophilic asthma. The proposed mechanism of action is that dexpramipexole 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.
In a Phase II study in participants with moderate-to-severe eosinophilic asthma, treatment with dexpramipexole resulted 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 addition, dose-dependent improvements in lung function were observed (Siddiqui et al. JACI. 2023). Oral dexpramipexole was well tolerated, with adverse events balanced across treatment and placebo groups.
Dexpramipexole is formulated as dexpramipexole dihydrochloride (75 mg and 150 mg dexpramipexole dihydrochloride are equivalent to 56 mg and 112 mg dexpramipexole, respectively). The doses administered in the dexpramipexole treatment groups mentioned throughout this document refer to dexpramipexole dihydrochloride.
About Eosinophilic Asthma
Asthma disrupts the lives of more than a quarter of a billion people worldwide. More than half of people with asthma have eosinophilic asthma which is driven by an elevated number of white blood cells called eosinophils, in the blood, tissue, and sputum. By inhibiting the maturation of eosinophils, we believe that oral administration of the investigational drug dexpramipexole acts to lower eosinophils. Currently approved injectable anti-IL-5/5R biologic therapies provide clinical benefit through eosinophil lowering.
The global asthma biologic market is experiencing robust growth, having doubled in the last three years, and is valued today at approximately $10 billion USD. If approved as a first-to-market oral therapy, dexpramipexole could provide an alternative to injectable biologics.
About Areteia
Areteia is a clinical-stage biotechnology company engaged in the development and delivery of a potential first-in-class oral therapy for inflammatory airway diseases, with an initial focus on severe eosinophilic asthma and eosinophilic chronic obstructive pulmonary disease. Areteia has advanced its investigational drug, dexpramipexole, into three separate Phase III clinical trials in eosinophilic asthma, including two 52-week global exacerbation trials (EXHALE-2 and EXHALE-3) and one 24-week lung function trial (EXHALE-4).
Areteia was created by Population Health Partners and Knopp Biosciences. A syndicate of leading life sciences and strategic investors has committed to invest up to $425 million USD in Series A financing to establish Areteia and advance dexpramipexole. To learn more, please visit www.areteiatx.com.
