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A7710 - Effectiveness of Acumapimod Oral P38 Inhibitor in the Treatment of Acute Severe Exacerbations of COPD: Results of the AETHER Phase II Trial
Author Block: J. A. Wedzicha1, A. MacKinnon2, J. M. Parkin2; 1National Heart and Lung Institute, London, United Kingdom, 2Mereo BioPharma Group plc, London, United Kingdom.
Rationale: Acute exacerbations of COPD (AECOPD) increase morbidity and drive lung function decline. Mitogen-activated protein kinase p38, a key regulator in the inflammation pathway, is activated in COPD and by triggers of exacerbations. Acumapimod, an oral, p38 inhibitor is being investigated for the treatment of acute exacerbations. A more effective anti-inflammatory therapy is expected to improve AECOPD outcomes.
Methods: NCT02700919 was a Phase II, randomised, multinational, double-blind, placebo-controlled study investigating the efficacy and safety of two dose regimens of acumapimod or placebo given over 5 days in addition to standard of care for acute exacerbations of COPD requiring hospitalisation. The primary endpoint was change from baseline in FEV1 to Day 7, with follow up to week 26 to determine efficacy on longer term outcomes, including treatment failures, recurrent exacerbations and safety.
Results: 282 patients were randomized. Acumapimod high and low dose regimens demonstrated a significant increase in FEV1 from baseline to Day 7 (p= 0.012, p ≤ 0.001). No significant change from baseline was shown for placebo (p=0.102). There was no statistical significance across the treatment groups.
In follow up to week 26 there was a significant reduction of > 50% (p ≤ 0.027 to 0.05) in the number of clinical treatment failures, in the high dose group compared to placebo, as measured by the number of re-hospitalisations for COPD at days 90 through 150 with numerical differences as early as day 30.
A trend of 56% to 28% reduction from day 30 through day 150 was also observed in the broader composite Clinical Treatment Failure scale (requirement for additional antibiotics or corticosteroids during either the initial or subsequent re-exacerbation, COPD rehospitalisation or death). This was observed in the high dose group compared to placebo or low dose, consistent with the rehospitalisation data.
Acumapimod was generally safe and well tolerated with the incidence and nature of adverse events as expected for this patient population. There were no drug-induced liver injuries and two cases of mild acneiform rash which fully resolved.
Conclusions: Acumapimod over 5 days of an acute exacerbation was well tolerated and demonstrated significant effects on need for re-hospitalisation for AECOPD. Acumapimod has demonstrated potential to deliver meaningful clinical benefits in the treatment of AECOPD through reduction in the patient and healthcare burden of treatment failures and recurrent exacerbations.