Investigational beta-2 adrenergic agonists for the treatment of chronic obstructive pulmonary disease

Expert Opin Investig Drugs. 2017 Mar;26(3):319-329. doi: 10.1080/13543784.2017.1287172. Epub 2017 Feb 6.

Abstract

Long-acting bronchodilators are pivotal in the therapeutic management of COPD patients with moderate-to-severe airflow obstruction. New ultra-long-acting β2-agnoists (ultra-LABAs) have been developed, some of which have been licensed for use as monotherapy and/or in combination with other bronchodilators or inhaled corticosteroids, for use in COPD patients with persistent symptoms and worsening airflow limitation. These new agents are faster in onset and have a prolonged duration of action, with a similar safety profile to the traditional twice-daily bronchodilators which may have an impact on patient concordance. Areas covered: A number of these ultra-LABAs are still under development and bi-functional hybrid molecules containing regions functioning as β2-agonists, and as muscarinic agonists (MABAs) has been developed. This review summarizes these (excluding the licensed ultra-LABAs) with attention on phase II studies data available to-date on their pharmacological profiles, clinical efficacy and safety, and future perspectives. Expert opinion: Despite all the new agents' available, the challenges that persist include any differences in efficacy and safety between the various possible LAMA/LABA combinations, relative advantages of MABAs over fixed-dose LAMA/LABAs, and the impact of these new molecules in terms of long term safety, especially in certain populations in co-morbidities frequently associated with COPD.

Keywords: Bronchodilators; COPD; COPD treatment; long acting beta agonists.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / pharmacology
  • Bronchodilator Agents / therapeutic use*
  • Delayed-Action Preparations
  • Drug Design
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Humans
  • Muscarinic Antagonists / adverse effects
  • Muscarinic Antagonists / pharmacology
  • Muscarinic Antagonists / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Delayed-Action Preparations
  • Drugs, Investigational
  • Muscarinic Antagonists