Asthma and COPD - roflumilast
Childhood asthma accounts for around a third of all sufferers, and is recognised as being the third leading cause of preventable hospitalisations in the US.
Drugs with longer duration and action and higher potency are needed to reduce dosing frequency, and oral availability would mean compliance with dosing regimens should be improved.
A new class of agents that fits the bill and is attracting attention is the phosphodiesterase IV inhibitors, which have a dual bronchodilatory and anti-inflammatory mechanism of action, relaxing the smooth muscles of the respiratory system and thus having a beneficial effect on the lung function of asthmatics. Altana's roflumilast is the furthest down the developmental pipeline.
In a placebo controlled randomised double blind two period crossover study, 16 patients with exercise induced asthma were given placebo or 500µg/day roflumilast for 28 days, randomly the active for 14 days followed by placebo for 14 days, or vice versa.1 Exercise challenge was performed 1 hour after dosing on days 1, 14 and 28.
Those taking the active were less affected by the exercise than those who had taken placebo, and had an improvement in lung function. Roflumilast was found to be well tolerated.
Another study has shown that it has potential for treating allergic rhinitis, or hayfever.2 A total of 25 subjects who suffered from hayfever but were asymptomatic were given placebo or 500µg oral roflumilast once a day and placebo for nine days each with a washout period of at least 14 days between the two. In each treatment period, the subjects were given controlled intranasal allergen provocation with pollen extracts for two hours each day from the third day of treatment. Airflow in the nose improved consistently while the patients were given roflumilast, and by the ninth day was significantly higher compared with placebo.
Roflumilast is now in Phase III trials for the treatment of asthma. Dose-finding studies have been completed for chronic obstructive pulmonary disease, and Phase III studies are now imminent.