*3.15. Synthetic Amino-Benzothiazoles*

The synthetic amino-benzothiazole dexpramipexole was first developed as a treatment for amyotrophic lateral sclerosis (ALS) and during the development program, a marked targeted depletion of BEC was observed in ALS patients; therefore, dexpramipexole holds promise for asthma and eosinophil-associated diseases [98].

In the EXHALE Phase II RCT [28,29], dexpramipexole (KNS-760704) orally administered at 37.5 mg, 75 mg, and 150 mg BID for 12 weeks was investigated in patients with poorly controlled moderate to severe eosinophilic asthma with an absolute BEC of ≥300 cells/μL. No differences were observed between dexpramipexole 37.5 mg and 75 mg and PCB in trough FEV1 and post-bronchodilator FEV1, while dexpramipexole 150 mg showed a numerical improvement in both outcomes vs. PCB at the end of the treatment period, and a significant increase in trough FEV1 at weeks 16/18 vs. PCB. The effect of treatment on the ACQ6 score was similar to that observed in the PCB group [28,29].

Dexpramipexole 37.5 mg, 75 mg, and 150 mg significantly (*p* < 0.05) reduced BEC vs. PCB (ratio to PCB of 0.45 (95%CI 0.23–0.87), 0.34 (95%CI 0.18–0.65), and 0.23 (95%CI 0.120.43), respectively). The FENO level numerically reduced upon treatment with dexpramipexole vs. PCB across all doses. No differences were observed between the treatment and PCB groups in terms of a change in AQLQ score [28,29]
