Tuesday, May 17, 2016

The discovery of roflumilast for the treatment of chronic obstructive pulmonary disease (2016 Expert Opinion on Drug Discovery)

Dear Respiratory friends, we are happy to present you exciting story of  discovery of roflumilast for the treatment of COPD by great Italian team: Mario Cazzola, Luigino Calzetta, Paola Rogliani & Maria Gabriella Matera.
Introduction: Cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE)4 is an intracellular target that can be exploited to the treat chronic obstructive pulmonary disease (COPD), given that it is expressed in all inflammatory cells implicated in this inflammatory airways disease. At the present time, roflumilast is the only PDE4 inhibitor that has received regulatory approval for use in patients with COPD.
Areas covered: The preclinical, clinical and post-marketing development of roflumilast is described. Furthermore, a critical analysis of the clinical data and positioning of this drug is undertaken in this review
http://www.tandfonline.com/doi/abs/10.1080/17460441.2016.1184642
 
Expert opinion: The identification of a subset of COPD patients, namely those suffering from severe airflow obstruction with symptoms of chronic cough and sputum and a history of previous exacerbations, as a specific target for roflumilast with the goal of reducing exacerbations, was entirely casual because the delineation of a “chronic bronchitis” responder group was clearly a post-hoc finding. However, it was useful to design prospective clinical trials that demonstrated reduced exacerbations in this specific subset of patients towards whom roflumilast therapy is now targeted. However, these pivotal trials still do not provide more accurate identification of the type of exacerbation to be treated by roflumilast. The identification of the right biological COPD exacerbation phenotype and/or the right clinical COPD phenotype are the only means that could justify the use of roflumilast as a first line anti-inflammatory therapeutic approach.
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2 comments:

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