Out-licensing

A New Generation Xanthine Bronchodilator Devoid of Major Cardiovascular Adverse Effects: Doxofylline in Phase III Clinical Trials for the Treatment of COPD and Bronchial Asthma

Introduction/Background

Doxofylline (7-(1.3-dioxalan-2ylmethl theophylline) is a novel xanthine bronchodilator, which differs from theophylline in that it contains a dioxalane group in position 7. Similarly to theophylline, its mechanism of action is related to the inhibition of phophodiesterase activities, but in contrast it appears to have decreased affinities towards adenosine A1 and A2 receptors, which may account for its better safety profile.

Aims/Hypothesis

We hypothesise that doxofylline will prove to be the next generation therapeutic for bronchial diseases, including asthma and chronic obstructive pulmonary disease.

Research

Bronchodilating activities of doxofylline have been demonstrated in clinical trials involving patients with either bronchial asthma or chronic obstructive pulmonary disease (COPD). Doxofylline was found to be particularly effective in both decreasing the daily asthma attack rate as well as the beta-2-agonist consumption. Phase III efficacy and safety testing for doxofylline in chronic reversible bronchial asthma was investigated in a double-blind randomised clinical trial. In this multicentre clinical trial doxofylline was shown to be equally effective when compared to theophylline, but with less adverse effects. Preliminary data have shown that oral doxofylline may induce favourable effects on inflammatory changes and altered cell proliferation of the airway mucosa in patients with chronic obstructive bronchitis. The safety profile shows a better tolerability on cardiovascular, digestive and the central nervous systems. Neither relevant alteration of sleep architecture, nor cardiac pro-arrhythmic actions nor gastric secretion stimulation have been reported in clinical trials. No relationship has been reported between Doxofylline serum levels and the occurrence of adverse events. The tolerability of doxofylline has been shown also in a retrospective open study in paediatric patients with bronchial asthma or airway obstruction complicating acute bronchitis.

Conclusion

In contrast to other xanthine bronchodilators, experimental and clinical studies have shown that the drug is devoid of direct stimulatory effects on systems other than the respiratory tract. This may be of importance because it may overcome limitations that currently prevent the use of xanthines in patients with asthma or COPD.

Relevance/Opportunity

We are currently seeking partners interested in the exclusive licensing of Doxofylline in Europe. Please enquire if you are interested in forming exclusive licensing partnerships regarding this novel drug.

Phase III