Dexpramipexole improves lung function in severe asthma: Study

Delhi: Dexpramipexole therapy reduced blood and tissue eosinophils in individuals with moderate to severe eosinophilic asthma, which is associated with improved lung function, seen from phase 2 of EXHALE trial. This study was carried out by Dr. Salman Siddiqui, MD, and his team, and the findings were first presented at the European Respiratory Society International Congress; Sept. 5-8, 2021 (virtual meeting).

Dexpramipexole is a medication that was first designed to treat amyotrophic lateral sclerosis. The medication did not fulfill its primary objective in the pivotal phase 2 and 3 study of amyotrophic lateral sclerosis, although it was shown to significantly reduce blood eosinophil counts with the degree of peripheral blood eosinophilia. With the results tipping towards a different direction, the team the researchers carried on to work towards the development in eosinophil-mediated immune diseases.

EXHALE is a multicentre, parallel-group, randomized, double-blind phase 2 experiment with 100 participants from 28 different locations around the United States. Following a 2-week open-label run-in period, participants were randomly allocated to daily dexpramipexole doses of 300 mg (n = 28), 150 mg (n = 26), 75 mg (n = 22), or placebo (n = 27). Two-thirds of patients were on moderate- to high-dose inhaled corticosteroid and long-acting beta-agonist treatment, and 20% to 30% fulfilled severe asthma criteria.

Key Findings:

 Over an 8- to 12-week period, the medication reduced eosinophils, supporting its influence on bone marrow and eosinophil maturation across all three tracing strata, as well as subsequent recovery on drug withdrawal over a further 12 weeks.

 In a predetermined analysis, nasal eosinophil peroxidase was decreased by 89 percent with 300 mg per day, 82.6 percent with 150 mg per day, and 35.5 percent with 75 mg per day, compared to 16.7 percent in the placebo group, at week 12.

 The researchers found a trend toward improved lung function compared to placebo with the 300 mg dexpramipexole dosage, although this trend was not statistically significant. This increase, however, attained statistical significance at week 8 and throughout the eosinophil recovery phase between weeks 16 and 18.

 There was no statistically significant or clinically meaningful difference in exhaled nitric oxide or Asthma Control Questionnaire-6 scores when any of the dexpramipexole dosages were compared to placebo.

 According to the announcement, dexpramipexole was well tolerated and there were no adverse effects that necessitated cessation.

In conclusion, the author said, "Our study supports the notion that dexpramipexole is a potent oral anti-eosinophilic agent in moderate to severe eosinophilic asthma, these data support further development of dexpramipexole in moderate to severe eosinophilic asthma."

References:

Siddiqui S, et al. ALERT: Asthma in adults, in children and ILDs. Presented at: European Respiratory Society International Congress; Sept. 5-8, 2021 (virtual meeting).