C. Prussin, T. Laidlaw, R. Panettieri
Feb 1, 2017
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0
Influential Citations
6
Citations
Quality indicators
Journal
The Journal of Allergy and Clinical Immunology
Abstract
Introduction Conclusions Dexpramipexole is an oral investigational drug serendipitously noted to lower blood eosinophils in prior clinical studies in amyotrophic lateral sclerosis. We sought to examine if dexpramipexole lowered blood and tissue eosinophils in an eosinophil-associated disease: chronic rhinosinusitis with nasal polyps (CRSwNP). Rationale: Dexpramipexole is an oral investigational drug serendipitously noted to lower blood eosinophils in prior clinical studies in amyotrophic lateral sclerosis. Methods: An open label study of dexpramipexole 300 mg/day was undertaken in 16 subjects with chronic rhinosinusitis with nasal polyps (CRSwNP) with a baseline blood absolute eosinophil count (AEC) ≥0.30x109/L and polyp eosinophilia. Co-primary endpoints examined were change in AEC and change in total polyp score (TPS), from baseline to end of study. Change in nasal polyp eosinophils was an exploratory endpoint. Data are shown from this ongoing study. Results: Baseline AEC was 0.525x109/L in the 16 subjects studied to date. AEC at month 6 was 0.031x109/L, a 94% reduction (p<0.001). Ten of the 16 subjects had eosinophil counts reduced to 0.020x109/L or less at month 6. There was no significant reduction in TPS. In the 12 subjects who had biopsies, polyp tissue eosinophilia was reduced from a mean of 233 to 5 eosinophils per high-powered field, a 97% reduction from baseline (p=0.001). Dexpramipexole was well tolerated with no drug related serious adverse events. Five subjects elected to continue on a long-term extension study. Conclusions: In sum, dexpramipexole is a well tolerated orally available drug with robust blood and tissue eosinophil lowering activity. Despite profound tissue eosinophil depletion, TPS was not significantly reduced. Given that eosinophil lowering by dexpramipexole is greater than or equal to that of current biologics, its clinical activity in asthma, where eosinophil lowering has been demonstrated to reduce exacerbations, and other eosinophil associated diseases is of great interest. Based on its oral administration, safety profile, and convenience, dexpramipexole has the potential for use by a broader segment of asthma patients than is currently indicated with approved biologics, including both moderate and severe asthmatics. Results 1. Dexpramipexole eosinophil-lowering activity was as great or greater than seen with current biologicals. 2. This suggests that dexpramipexole may have utility in eosinophilic asthma and other eosinophil-associated diseases. 3. Two subjects were noted to have substantial polyp tissue eosinophil lowering but minimal lowering in blood. This suggests the possibility that dexpramipexole may have direct activity on tissue eosinophil poiesis. Study Demographics, n= 16 subjects Characteristic Value Age (y) 43.9 (7.5)* Gender 9M/7F Race 13 white 3 African American Weight (kg) 90.3 (23.8)* Body Mass Index (kg/m2) 29.1 (5.4) Previous Sinonasal surgery, n (%) 14 (87.5%) Number of Sinus Infections (past 12 months) 1.9 (1.75)* Duration of Symptoms (y) 10.2 (12.1)* Asthma History, n (%) 13 (81.3) FEV1 (% predicted) 88 (20) Serum IgE (KIU/L) 219 (371)* History of aspirin sensitivity 7 subjects (44%) Dexpramipexole effectively lowers blood eosinophils B lo od a bs ol ut e eo si no ph il co un t