In the EXHALE-1 study, dexpramipexole significantly reduced blood absolute eosinophil count (AEC) at week 12 versus placebo
All three active doses achieved significance (150-mg, 75-mg, and 37.5-mg BID)
Dexpramipexole displayed a favorable safety profile and was well tolerated, with 97% of treated subjects completing the primary assessment phase.
CHAPEL HILL, N.C.–(BUSINESS WIRE)–Areteia Therapeutics, Inc. (“Areteia”) today announced that results from the Phase II EXHALE-1 study of dexpramipexole have been published online in the Journal of Allergy and Clinical Immunology (JACI). The study sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma.
Dexpramipexole significantly reduced AEC at week 12 across all doses tested, with 77% and 66% reductions relative to placebo in the 150-mg and 75-mg twice daily (BID) dose groups, respectively. Dexpramipexole reduced the exploratory end point of nasal eosinophil peroxidase, a biomarker of tissue eosinophilic inflammation, in both the 150-mg BID and the 75-mg BID groups. Clinically meaningful improvements in lung function as measured by forced expiratory volume (FEV1) were observed starting at week 4. Dexpramipexole displayed a favorable safety profile.
About the EXHALE-1 STUDY
Methods
The study was a randomized, double-blind, placebo-controlled proof-of-concept trial in adults with inadequately controlled moderate to severe asthma and AEC greater than or equal to 300/μL. Subjects were randomly assigned (1:1:1:1) to dexpramipexole 37.5-mg BID, 75-mg BID or 150-mg BID 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).
Overall, dexpramipexole was found to be safe and well tolerated. Rates of adverse events were balanced across treatment arms, with no serious adverse events or discontinuations due to adverse events reported. Of 76 dexpramipexole-treated subjects, 74 (97%) completed the primary assessment phase on the study drug.
For more information on the study publication and results: https://www.jacionline.org/action/showPdf?pii=S0091-6749%2823%2900709-1
About Areteia Therapeutics
Areteia Therapeutics, Inc. (areteiatx.com) is a clinical stage biotechnology company whose purpose is to develop and deliver novel Inflammation and Immunology (I&I) therapies that put respiratory patients in better control of their disease – and back in control of their lives. Our initial focus is developing the first potential oral drug for eosinophilic asthma. Areteia’s lead drug candidate is dexpramipexole, a first-in-class oral eosinophil maturation inhibitor.
Areteia was created by Population Health Partners and Knopp Biosciences. A syndicate of leading life sciences and strategic investors led by Bain Capital Life Sciences with participation from Access Biotechnology, GV, ARCH Venture Partners, Saturn Partners, Sanofi, Maverick Capital, and Population Health Partners, has committed to invest up to $350 million in Series A financing to establish Areteia and advance dexpramipexole through Phase III clinical trials, secure commercial supply, and pursue potential next-generation medicines.
Areteia has initiated late-stage development of dexpramipexole in eosinophilic asthma, including three Phase III clinical trials in partnership with Population Health Partners’ development unit, Validae Health.
About Dexpramipexole
Dexpramipexole is an oral small molecule eosinophil lowering drug currently in Phase III development for eosinophilic asthma. Dexpramipexole inhibits the maturation of eosinophils in the bone marrow, based on evidence from cell cultures and human biopsies, thereby lowering peripheral blood eosinophil levels. Most recently in a Phase II study in patients with moderate-to-severe eosinophilic asthma, treatment with dexpramipexole resulted in a significant, dose-dependent reduction in blood absolute eosinophil count at all doses tested (twice daily dexpramipexole doses of 37.5-mg, 75-mg, or 150-mg) compared to placebo. Dexpramipexole was well tolerated in the trial, with adverse events balanced across treatment and placebo groups, no serious adverse events, and no adverse events leading to discontinuation.
About Eosinophilic Asthma
Asthma disrupts the lives of more than a quarter of a billion people worldwide. More than half of asthma patients have eosinophilic asthma, which is driven by an oversupply of eosinophils, a type of white blood cell, in blood and tissue. By inhibiting the maturation of eosinophils, oral dexpramipexole acts in a way similar to injectable anti-IL-5 biologic therapies. The asthma biologic market is experiencing growth of 10% per year and is valued at around $8 billion, with IL-5 biologic therapies representing approximately $3 billion of that figure. If approved as a first-to-market oral, dexpramipexole could provide a compelling alternative to injectable biologics, and could potentially be used earlier in the asthma treatment paradigm to prevent progression of disease.
Contacts
Tamsin Berry
Tamsin.Berry@areteiatx.com
Mark Kreston
Mark.Kreston@areteiatx.com