Background:

Metalloproteinase MMP-12 plays a role in asthma pathophysiology and is associated with disease severity

Adermastat-(FP-025), a small MMP-12 inhibitor molecule, showed sustained anti-inflammatory effects and attenuated allergen-induced histopathology in a mouse model of house dust-mite (HDM) allergic asthma and was deemed safe in healthy volunteers

Aim:

To assess the efficacy of multiple oral doses of Adermastat (FP-025) in HDM-allergic asthma

Methods:

19 HDM-allergic asthmatics (stable; FEV1?70% pred; blood eosinophils ?150 cells/mcL; demonstrated HDM-induced late response (LAR)) participated in a randomized, double-blind, 2-way cross-over study (3-7 weeks washout between Study Periods). Subjects took FP-025 (400 mg) or Placebo (P) BID for 12 days; a HDM challenge was performed on Day-11. Airway responses to HDM were recorded 0-8hours post-allergen and expressed as %change in FEV1 from baseline. Differences in areas under the response-time curves (AUC) were analyzed using paired t-test and ANOVA

Results:

Overall, Adermastat-(FP-025) was safe and well-tolerated. A carry-over effect of FP-025 was found on LAR (AUC3-8h) comparing the sequences: FP-025-P vs. P-FP-025 (p=0.0340). In the P-FP-025 sequence, FP-025 significantly reduced LAR vs. P (mean+/-SD: AUC3-8h 84.01 (54.41) and 113.43 (48.6), respectively; p=0.0161, with similar outcomes when P (Period 1) was compared with FP-025 (Period 1+2): (mean+/-SD AUC3-8h 80.83 (47.33)); p=0.0149. LAR was not statistically different between randomization sequences FP-025 (mean+/-SD: 78.51 (44.12) and 84.01 (54.41), resp, p=0.8109)

Conclusion:

Adermastat-(FP-025) was safe and demonstrated promising results in allergic asthma patients.