Dexpramipexole reduces blood, nasal eosinophils in patients with asthma

Key takeaways:

• Reductions in eosinophil counts were observed as early as weeks 4 to 6.
• Absolute eosinophil counts returned to normal within 8 weeks of the end of treatment.
• No serious adverse events occurred.

Treatment with dexpramipexole decreased eosinophil levels and improved FEV₁ among adults with asthma with no serious adverse events, according to a study published in The Journal of Allergy and Clinical Immunology.

As an oral drug, dexpramipexole (Areteia Therapeutics) may be an alternative for other treatments that rely on injections, Salman Siddiqui, BM, FRCP, PhD, professor, National Heart and Lung Institute, Imperial College, and colleagues wrote.

In previous studies, dexpramipexole reduced blood and tissue eosinophils with indications that it inhibits eosinophil maturation with a profile that resembles anti-IL-5 and IL-5 receptor biologics used to treat asthma, the researchers said.

The EXHALE study comprised 103 patients (median age, 44 years; 73.8% white; 52.4% women) aged 18 to 74 years with moderate to severe eosinophilic and uncontrolled asthma on steps 3 through 5 of Global Initiative for Asthma therapy.

Groups included 22 patients on 37.5 mg of dexpramipexole, 24 patients on 75 mg, 28 on 150 mg, and 25 on placebo, all twice a day, who finished 12 weeks of treatment and the primary assessment phase.

The researchers reported reductions in eosinophil levels beginning between weeks 4 and 6. Placebo-corrected absolute eosinophil counts (AEC) ratios to baseline at week 12 included:

1. 0.23 (95% CI, 0.12-0.43) for a 77% reduction in the 150 mg group;
2. 0.34 (95% CI, 0.18-0.65) for a 66% reduction in the 75 mg group; and
3. 0.45 (95% CI, 0.23-0.87) for a 55% reduction in the 37.5 mg group.

A log-linear dose-response analysis indicated a statistically significant dose response as well, the researchers said. AEC gradually returned to pretreatment levels by week 20 after treatment stopped.

Additionally, in the 150 mg group, basophils fell by 44% (P = .029) based on flow cytometry and by 29% (P = .048) based on automated differential.

Nasal eosinophil peroxidase (EPX) fell in the treatment groups as well, with a median ratio of 0.11 (interquartile range [IQR], 0-0.94; P = .02) and an 89% reduction for the 150 mg group and a median ratio of 0.15 (IQR = 0-0.71; P = .021) and an 85% reduction for the 75 mg group.

There were high correlations between nasal EPX ratio to baseline and reductions in blood AEC at week 12 as well, the researchers said.

Although totals in the pooled 75 mg and 150 mg groups did not achieve statistical significance at week 12, the researchers said that they did observe increases of varying magnitudes and significances in prebronchodilator FEV₁ across study groups and visits. Improvements in FEV₁ persisted after treatment through weeks 16 and 18 as well.

There also was a correlation between prebronchodilator FEV₁ change and AEC change, both from baseline at week 12, with a correlation coefficient of 0.58, among the pooled 75 mg and 150 mg groups.

When the researchers classified all the patients into a group with 50% reductions or greater in their eosinophils and a group with less than 50% reductions at week 12, the group with the greater reductions had larger improvements in FEV₁.

Further, the 150 mg group had a 183 mL (95% CI, 20.3-350) placebo-corrected change averaged over all study visits.

This group also had incremental but nonsignificant improvements in its 6-item Asthma Control Questionnaire scores, Asthma Quality of Life Questionnaire scores and fractional exhaled nitric oxide totals.

The researchers called dexpramipexole safe and well tolerated as well, with 74 of 76 treated patients (97%) completing the primary assessment phase. There were no serious adverse events or deaths reported.

Percentages of patients who experienced treatment-emergent adverse events during the primary assessment phase and during the 30 days afterward included 31.8% of the 37.5 mg group, 46.2% of the 75 mg group, 42.9% of the 150 mg group and 33.3% of the placebo group.

Most of the adverse events in the treatment groups were mild to moderate, with three severe events that the researchers did not believe were related to the treatment. Also, the researchers did not believe that the pattern of specific adverse events was dose-related.

Based on these findings, the researchers concluded that dexpramipexole significantly reduced counts of blood eosinophils among patients with moderate to severe eosinophilic asthma in a dose-dependent manner, with significant reductions in nasal EPX as well.

The researchers called these reductions comparable with reductions seen in blood and sputum eosinophils achieved with anti-IL-5 biologics, indicating that dexpramipexole may deliver similar clinical benefits for patients with asthma in an oral format instead of injections, which these other biologics use.