An update and appraisal of the cilomilast Phase III clinical development programme for chronic obstructive pulmonary disease

Br J Clin Pharmacol. 2006 Aug;62(2):138-52. doi: 10.1111/j.1365-2125.2006.02640.x.


Cilomilast (Ariflo, SB 207499) is an orally active, second-generation phosphodiesterase (PDE) 4 inhibitor that is being developed by GlaxoSmithkline for the treatment of chronic obstructive pulmonary disease (COPD). The results of Phase I and Phase II studies have demonstrated that cilomilast significantly improves lung function and quality of life to a clinically meaningful extent, which has led to a comprehensive Phase III programme of research evaluating efficacy, safety and mechanism of action. However, the results of those Phase III studies are unremarkable and disappointing, raising doubt over the future of cilomilast as a novel therapy for COPD. This review summarizes data obtained from the Phase III clinical development programme, highlights some of the potential concerns both specific to cilomilast and to PDE4 inhibitors in general and assesses the likelihood that cilomilast will reach the market.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • Adult
  • Aged
  • Aged, 80 and over
  • Carboxylic Acids / adverse effects
  • Carboxylic Acids / therapeutic use
  • Clinical Trials, Phase III as Topic
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclohexanecarboxylic Acids
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Phosphodiesterase Inhibitors / adverse effects
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Research Design
  • Respiratory Function Tests / methods
  • Treatment Outcome


  • Carboxylic Acids
  • Cyclohexanecarboxylic Acids
  • Nitriles
  • Phosphodiesterase Inhibitors
  • Cilomilast
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4