A new approach in a challenging disease
A New Approach
Stopping eosinophils before they can cause damage.
Like other blood cells, eosinophils originate as stem cells in the bone marrow. They differentiate and mature into eosinophils through complex molecular signaling and interactions with surrounding tissues, primarily in the bone marrow. Inflammatory signals—from the asthmatic lung, for example—may increase production of mature eosinophils. This increases eosinophil counts in the blood and ultimately in the lungs, causing tissue
remodeling, mucus secretion, airway trapping, and asthma attacks.
If approved, dexpramipexole will be a first-in-class eosinophil maturation inhibitor that targets eosinophilic inflammation by lowering blood and tissue eosinophils.
Like other blood cells, eosinophils originate as stem
cells in the bone marrow. They differentiate and mature
into eosinophils through complex molecular signaling
and interactions with surrounding tissues, primarily in
the bone marrow. Inflammatory signals—from the
asthmatic lung, for example—may increase production
of mature eosinophils. This increases eosinophil counts
in the blood and ultimately in the lungs, causing tissue remodeling, mucus
secretion, airway trapping, and
asthma attacks.
Dexpramipexole inhibits the maturation of eosinophils at an early stage, preventing their travel through the blood to the lung, according to evidence from cell cultures and human biopsies.
Not treated.
Large epidemiology studies have shown that
eosinophil counts in the bloodstream may predict
the risk of asthma exacerbations.
Treated with dexpramipexole.
Across five clinical trials, dexpramipexole
significantly reduced eosinophils in blood and
inflamed tissue and improved lung function in
patients with eosinophilic asthma.
How Did We Get Here?
The eosinophil-targeting effects of oral dexpramipexole were discovered during its clinical development. Across five clinical trials, dexpramipexole showed a significant reduction in eosinophil counts in both the blood and in inflamed tissue.
The most recently completed dexpramipexole trial was the EXHALE-1 trial, a Phase II study in participants 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 (dexpramipexole doses of 37.5 mg, 75 mg, or 150 mg twice daily) compared to placebo. While the trial was not powered to assess lung function, patients receiving the highest dexpramipexole dose showed clinically relevant increases in FEV1 (the amount of air a subject can forcibly exhale in one second). 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.
Areteia is advancing dexpramipexole through Phase III clinical trials which will potentially support approval of dexpramipexole for the treatment of eosinophilic asthma. To our knowledge, dexpramipexole is the only late-stage oral treatment in development for eosinophilic asthma.
Phase III Development Program - Dexpramipexole
Phase III development is underway.
Following the successful Phase II EXHALE-1 trial of dexpramipexole in moderate-to-severe eosinophilic asthma, Areteia is conducting three Phase III trials in patients with eosinophilic asthma.
- Randomized, double-blind, placebo-controlled study to assess the effects of two different doses of dexpramipexole on exacerbation rates and lung function.
- Inadequately controlled GINA 4/5 patients
- 75 mg, 150 mg, Placebo–BID (twice a day)
- Global study (N = 1,395)
- Randomized, double-blind, placebo-controlled, study to assess the effects of two different doses of dexpramipexole on exacerbation rates and lung function.
- Inadequately controlled GINA 4/5 patients
- 75 mg, 150 mg, Placebo–BID (twice a day)
- Global study (N = 930)
