The oral asthma therapy dexpramipexole significantly reduced blood eosinophil counts and was well tolerated in patients with inadequately controlled moderate to severe eosinophilic asthma, investigators reported in the Journal of Allergy and Clinical Immunology.

Dexpramipexole, an oral therapy initially developed to treat amyotrophic lateral sclerosis (ALS), was unexpectedly found to decrease blood eosinophil counts and has since been tested for the treatment of respiratory conditions. The EXHALE trial ( Identifier: NCT05763121), a randomized, double-blind, parallel-group, placebo-controlled, phase 2 proof-of-concept study, evaluated the efficacy of dexpramipexole in moderate to severe eosinophilic asthma that was inadequately controlled (ie, uncontrolled on Global Initiative for Asthma [GINA] 3-5 therapy). The study was conducted at 35 US sites.

Participants were aged 18 to 74 years, diagnosed with moderate-to-severe asthma based on GINA 2018 guidelines of at least 12 months, and required daily treatment with a minimum of low-dose inhaled corticosteroid combined with a long-acting β2 agonist on a stable dose for at least 1 month before screening. Trial participants received twice-daily dosing of study drug or placebo for 12 weeks, followed by a 12-week washout. The trial’s primary endpoint was the relative change in blood absolute eosinophil count (AEC) at week 12.

A total of 103 patients were randomly assigned into 1 of 4 treatment groups from August 15, 2019, to August 28, 2020: dexpramipexole 37.5 mg (n=22), 75 mg (n=26), or 150 mg twice-daily (n=28), or placebo (n=27). The primary assessment phase on study drug was completed by 96% of participants overall and 97% of dexpramipexole-treated patients. Participants’ overall median age was 44.0 years, 52.4% were female, and 73.8% were White.

As a well-tolerated oral drug, dexpramipexole may provide an alternative to current injected biologic therapies.

Eosinophil lowering occurred beginning at weeks 4 to 6. The week 12 placebo-corrected AEC ratio to baseline was 0.23 (95% CI, 0.12-0.43, P <.0001) in the 150 mg group, 0.34 (95% CI, 0.18-0.65; P =.0014) in the 75 mg group, and 0.45 (95% CI, 0.23-0.87, P =.019) in the 37.5 mg group, for decreases of 77%, 66%, and 55%, respectively. The study drug was stopped at week 12, and AEC gradually returned to pretreatment levels by week 20.

Nasal eosinophil peroxidase (EPX), which is highly correlated to sputum eosinophil count, also decreased significantly during the trial. The highest decrease in EPX was for the 150 mg group (median ratio, 0.11; interquartile range [IQR], 0.00-0.94; P =.020) and 75 mg group (median ratio, 0.15; IQR, 0.00-0.71; P =.021), for reductions of 89% and 85%, respectively. Nasal EPX ratio to baseline was highly correlated with blood AEC lowering at week 12.

The pre-bronchodilator forced expiratory volume in 1 second (FEV1) in the pooled 75 mg and 150 mg groups did not achieve statistical significance at week 12, at which point formal statistical testing was stopped.

In a post-hoc analysis of pre-bronchodilator FEV1 in each dexpramipexole group averaged across all study visits, the 150 mg group resulted in a placebo-corrected change from baseline of 183 mL (20.3 to 350, P =.029, nominal value).

Treatment-emergent adverse events (AEs) in the primary assessment phase and 30 days afterward occurred in 31.8%, 46.2%, and 42.9% of participants in the 37.5 mg, 75 mg, and 150 mg dexpramipexole groups, respectively, vs 33.3% in the placebo group. No serious AEs or deaths occurred, and a majority of AEs in the dexpramipexole groups were mild to moderate in severity.

Study limitations include the sample size and duration.

“As a well-tolerated oral drug, dexpramipexole may provide an alternative to current injected biologic therapies,” stated the investigators.

Disclosure: This work was funded by Knopp Biosciences, LLC. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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