BCT-197 (acumapimod) is an oral p38 MAP kinase inhibitor that has completed Phase 2 development as first-line therapy for severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Acumapimod is given during a severe exacerbation to reduce the risk of further exacerbations.

AECOPD is characterized by a sudden worsening in the COPD patient’s symptoms of dyspnoea, cough and sputum production. These episodes typically last for several days and often require hospitalization of the patient and an increase in medication. Severe exacerbations are where the patient is hospitalised or visits the emergency room. The number of acute exacerbations a patient experiences on an annual basis is directly related to mortality. AECOPDs occur in the natural course of the disease but are commonly triggered by infections and air pollution. BCT-197 aims to address the airway and systemic inflammation that are characteristic drivers of the disease and to reduce the frequency of subsequent severe AECOPDs.

Clinical Status

We have completed a Phase 2, double-blind, randomized, placebo-controlled clinical trial in 282 patients under a US IND investigating the use of BCT-197, on top of SoC, for the treatment of patients with AECOPD. The study met the primary endpoint of change in forced expiratory volume in 1 second (FEV1) at day 7 versus baseline in both the low and high dose regimens.

Importantly there was a statistically significant reduction (>50%) in hospital readmissions for re exacerbations of COPD at 90 to 150 days for the high dose regimen, with a trend observed as early as 30 days. This long-term clinical effect is supported by the statistically significant reductions in both the key inflammatory biomarkers, hsCRP and fibrinogen, following treatment with BCT-197, with hsCRP remaining suppressed through the 26-week observation period.

Further analysis of the most severe patients, (patients who experienced ≥2 exacerbations in the previous year), showed a 46% reduction in the number of patients who suffered a subsequent moderate or severe re-exacerbation. Consistent with the results from this trial, there was a reduction in the percentage of patients receiving antibiotic and systemic steroid use in the high-dose group versus placebo of 46% observed in the long-term follow-up portion of the trial.

A total of 514 subjects have received BCT-197 to date in Phase 1/2 clinical studies and the therapy has been safe and well tolerated.

Following the Phase 2 trial Mereo announced a successful End of Phase 2 Meeting with FDA.

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Scientific publications and public presentations

Wedzicha JA , MacKinnon A and Parkin J. Effectiveness of Acumapimod Oral P38 Inhibitor in the Treatment of Acute Severe Exacerbations of COPD: Results of the AETHER Phase II Trial. American Journal of Respiratory and Critical Care Medicine (conference supplement) 2018; Vol 197: A7710.

Treatment of acute exacerbations in COPD: an exploratory Phase II study of single and repeated doses of acumapimod (BCT197), an oral p38 inhibitor: American Thoracic Society meeting, 2017

Strambu et al (2019). Phase II Study of Single/Repeated Doses of Acumapimod (BCT197) to Treat Acute Exacerbations of COPD.  COPD Nov 4:1-10.

 

 

View Acumapimod Abstract and Poster

REFERENCES

  1. National Heart, Lung and Blood Institute (accessed in Dec 2017) 
  2. COPD Coalition
  3. Mannino et al (2002) MMWR Survell Summ 51: p1-6 
  4. Wier et al (2011) AHRQ, HCUP, Statistical Brief #106 p1-11
  5. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019
  6. De Buck et al (2015) Population PK-PD Model for Tolerance Evaluation to the p38 MAP Kinase Inhibitor BCT197. CPT Pharmacometrics Syst. Pharmacol. 4, 691–700


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