Acumapimod Significantly Reduces Key Inflammatory Biomarkers in Severe COPD Exacerbations and Reduces the Rate of Re-Hospitalization

Abstract RATIONALE: Acumapimod is a potent, oral inhibitor of p38 MAPK being studied in acute severe exacerbations of COPD (AECOPD). Acumapimod has demonstrated a significant reduction in the rate of re-hospitalization following treatment for an index severe AECOPD. Here we review the biomarker data observed with acumapimod treatment. METHODS: In the Phase 2 AETHER study (NCT02700919), 2 dose regimens of acumapimod were compared to placebo in the treatment of severe AECOPD. Patients were treated with acumapimod on days 1, 3 and 5 with either 75mg/40mg/40mg or 40mg/20mg/20mg. 282 patients were randomized 1:1:1 (high/low/plb) on top of standard care (including systemic corticosteroids and antibiotics). Biomarkers assessed included hsCRP and fibrinogen. RESULTS: Both doses of acumapimod significantly increased FEV1 from baseline at Day 7 (primary endpoint) by (mean [SE]): 84mL (0.03, p=0.012) on high dose acumapimod and 115mL (0.03, p<0.001) on low dose acumapimod. Further, high dose acumapimod significantly reduced the rate of re-hospitalisations for AECOPD compared to placebo by 50.3% (per protocol population, p=0.043). Both doses of acumapimod reduced fibrinogen and hsCRP compared to placebo, with the largest reductions observed on high dose acumapimod. At Day 7, change from baseline for fibrinogen was (mean [SD]): -1.49 (1.09) g/L for the high dose, -1.22 (0.93) g/L for the low dose and -0.65 (1.05) g/L for placebo. At Day 7, change from baseline for CRP was (mean [SD]): -16.70 (41.22) mg/L for the high dose, -10.42 (40.75) mg/L for the low dose and -5.34 (22.22) mg/L for placebo. Similar effects on biomarkers were noted in populations at baseline with either <2% eosinophils or ≥2%; the effect on reducing re-hospitalizations in the high dose arm was also observed similarly regardless of eosinophil status at baseline. CONCLUSIONS: Acumapimod at a dose of 75mg/40mg/40mg showed significant reductions in hsCRP and fibrinogen in AECOPD. More effective control of inflammation during an exacerbation may reduce treatment failure and exacerbation recurrence. Acumapimod has been shown to significantly reduce the rate of subsequent severe AECOPD; confirmatory studies are planned to substantiate these effects in this area of significant unmet need.