Argenta Discovery Publishes Positive Data From a Phase II Proof of Concept Trial with Co-Administration of Inhaled ADC4022 Plus Budesonide Study in COPD
Harlow, UK, 15 Sept 2009 - Argenta Discovery Limited, the respiratory drug development company, presented promising data from a Phase II chronic obstructive pulmonary disease (COPD) trial at the European Respiratory Society meeting in Vienna. The trial investigated the effect of ADC4022 (low-dose inhaled theophylline) in a co-administration study with inhaled budesonide.
Pre-clinical studies undertaken by Argenta have indicated that ADC4022 and inhaled corticosteroids have little effect on lung inflammation when given separately, but are synergistic when given together. The aim of the four week Phase II study with ADC4022 was to assess whether the activity of inhaled corticosteroids in COPD, which are relatively ineffective when given alone, can be enhanced by the addition of ADC4022 and bring a meaningful improvement in the treatment of this condition.
The study showed that there was a significant beneficial treatment effect on lung function over the four week treatment period in COPD patients treated with ADC4022 and budesonide compared to those patients treated with placebo and budesonide. In addition, changes in markers of inflammation in both sputum and biopsy were observed after co-administration of ADC4022 and budesonide by the inhaled route.
“These data are very encouraging, given the short treatment period and the relatively small number of subjects studied, and are supportive of an enhanced pharmacological effect for the inhaled combination therapy. If these findings can be confirmed in longer term trials, they would also be expected to result in significant benefit for patients including reduction in the incidence and severity of exacerbations and improvement in quality of life”, said Professor Neil Barnes, Principal Investigator for the study.
Commenting on the results, Dr. Christopher Ashton, Argenta’s CEO, said, “The development of a safe, well tolerated and effective anti-inflammatory drug for COPD is one of the key goals for the pharmaceutical industry. This study emphasises the significant potential of an inhaled combination of low-dose theophylline with an inhaled corticosteroid to provide an effective therapy for COPD and steroid-resistant asthma. As part of our further development of this exciting approach, we are currently planning a follow-on three month dose-ranging study”.
About the Study
The study was conducted in patients with moderate to severe COPD. Following a four week pre-treatment period with nebulised budesonide (1mg twice daily), patients then received either nebulised ADC4022 (12.5mg) or placebo twice daily in addition to budesonide for a further four weeks (n=91). Data from the study demonstrated that, in the absence of long-acting bronchodilator therapy, there was a favourable treatment effect on pulmonary function in patients who received nebulised ADC4022 co-administered with budesonide, compared to patients who received placebo plus budesonide (treatment differences at four weeks for FEV1 and FVC were 142 and 281 mL respectively, p<0.05). Consistent with this effect on lung function, 20% fewer subjects required rescue medication (ipratropium) on ADC4022 treatment compared to placebo.
In addition, there were changes in inflammatory cell populations that were also indicative of a pharmacological effect of ADC4022 + budesonide in the lung. In the sputum, an increase in % sputum neutrophils (p=0.089) was observed that was associated with a concordant decrease in % macrophages in the ADC4022 + budesonide group compared to the placebo + budesonide group. In bronchial biopsies from a small cohort of patients (n=30), CD8+ T cells and CD68+ macrophages were reduced (p=0.141 and p=0.181, respectively); supporting the anti-inflammatory effect of ADC4022 when co-administered with budesonide.
There were no serious adverse events attributable to the co-administration of ADC4022 and budesonide. The excellent tolerability for inhaled ADC4022 was reflected in the low systemic exposure of theophylline at concentrations that were at least 20-fold lower than those required for oral activity as a bronchodilator.
Clinical trial identifier: NCT00634413
Oral communication presented at the ERS in Vienna: Monday, 14
September 2009. Room
Session: New drugs for airways disease
Notes to Editors
Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow obstruction that is progressive and current therapies, including inhaled corticosteroids, fail to treat disease progression. COPD is a leading cause of morbidity and mortality worldwide with an overall prevalence in adults over 40 years currently estimated at between 9 and 10%. Unlike many other major diseases, deaths due to COPD are increasing and the World Health Organisation (WHO) estimates by 2030 that COPD will be the third leading cause of mortality and fifth leading cause of morbidity in the world. Thus there is a high level of unmet medical need for this progressive and debilitating disease.
About Argenta Discovery
Argenta Discovery Limited, founded in August 2000, is focused on developing therapies for chronic respiratory diseases, including COPD, severe asthma and cystic fibrosis. The company is developing a portfolio of anti-inflammatory programmes with the goal of demonstrating clinical proof-of-concept. Argenta also has a contract research division that provides integrated drug discovery services to a range of leading pharmaceutical and biotechnology companies worldwide. Argenta is headquartered in Harlow, UK. For more information about Argenta Discovery, please visit www.argentadiscovery.com
Argenta Discovery Limited
Dr Christopher Ashton, CEO
Dr Mary Fitzgerald, EVP Respiratory
+ 44 (0) 1279 645 645
Posted: September 2009