Efficacy of indacaterol in the treatment of patients with COPD

Jones, Paul; Barnes, Neil; Vogelmeier, Claus; Lawrence, David; Krämer, Benjamin

doi:10.4104/pcrj.2011.00066

Cited by 20 publications

(14 citation statements)

References 32 publications

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“…Indacaterol is a newly approved once daily LABA that shows superior bronchodilatory activity compared with salmeterol or formoterol but equivalency to the muscarinic antagonist tiotropium for forced expiratory volume in 1 second (FEV1) (Jones et al, 2011). Recently, the novel anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor roflumilast (Daxas; Daliresp; Takeda Pharmaceuticals Korea Co., Ltd., Seoul, Korea) has been approved in the United States and the European Union for COPD GOLD stage 3 and 4 patients with bronchitis, where it is used as an add-on therapy to LABA treatment (Cazzola, 2010).…”

Section: Introductionmentioning

confidence: 99%

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β₂-Adrenoceptor Agonist

Tannheimer

Sorensen

Cui

et al. 2014

J Pharmacol Exp Ther

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Inhaled long-acting b 2 -adrenoceptor agonists (LABA) that act as bronchodilators and the oral anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor roflumilast are both approved therapies for chronic obstructive pulmonary disease (COPD). Here we describe the activity of a novel, inhaled, bifunctional, small molecule (, which has specific b 2 agonist and PDE4 inhibitory activity. GS-5759 demonstrated potent and full agonist activity at b 2 adrenoceptors (EC 50 5 8 6 4 nM) and is a potent inhibitor of the PDE4 enzyme (IC 50 5 5 6 3 nM). In cell assays, GS-5759 inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor a (TNFa) production in human peripheral mononuclear cells (PBMC) with an IC 50 5 0.3 nM [confidence interval (CI) 0.1-0.6] and in human neutrophils formyl-methionyl-leucyl-phenylalanine (fMLP)-induced super oxide anion production with an IC 50 5 3 nM . The addition of the b 2 antagonist ICI 118551 shifted the IC 50 in these cell assays to 4 and 38 nM, respectively, demonstrating the contribution of both b 2 agonist and PDE4 inhibitory activity to GS-5759. GS-5759 was also a potent inhibitor of profibrotic and proinflammatory mediator release from human lung fibroblasts. GS-5759 relaxed guinea pig airway smooth muscle strips precontracted with carbachol in a concentrationdependent manner with an EC 50 5 0.5 mM (CI 0.2-2) and had slow dissociation kinetics with an Off T 1/2 . 720 minutes at an EC 80 concentration of 3 mM. GS-5759 is a novel bifunctional molecule with both potent b 2 agonist and PDE4 inhibitor activity that could provide inhaled bronchodilator and anti-inflammatory therapy for COPD.

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Section: Introductionmentioning

confidence: 99%

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β₂-Adrenoceptor Agonist

Tannheimer

Sorensen

Cui

et al. 2014

J Pharmacol Exp Ther

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“…Extensive preclinical studies on indacaterol have documented its rapid onset and long duration of action due to its biochemical structure 51–53. The speed of bronchodilation is similar to that of salbutamol (ie, both of five minutes) and longer than that of traditional LABA (ie, 24 hours) such as salmeterol and formoterol, which require twice-daily administration.…”

Section: Indacaterol: An “Ultra-laba”mentioning

confidence: 99%

Indacaterol: a comprehensive review

Rossi¹,

Polese²

2013

COPD

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At present there is no cure for chronic obstructive pulmonary disease (COPD). However, some nonpharmacologic treatments, such as rehabilitation and lung volume reduction surgery, as well as pharmacologic intervention, can relieve some of the patient’s symptoms and improve quality of life, while also reducing the rate of exacerbations and hospitalizations. There needs to be a paradigm shift away from the unjustified nihilistic approach to COPD towards considering it a preventable and treatable disease. After patients quit smoking and start to lead healthier lifestyles, long-acting bronchodilators, such as long-acting beta-adrenergic agents (LABA) and long-acting antimuscarinic agents (LAMA), are recommended as the cornerstone of treatment for COPD, either as monotherapy or in combination. COPD is characterized by a reduced maximum expiratory flow and slow forced emptying of the lungs, which progress over time and are not completely reversible. In this condition, gas gets trapped in the lungs and pulmonary hyperinflation occurs. LABA and LAMA improve airway patency and deflate the lungs. Indacaterol is the first once-daily LABA approved for treatment of COPD, and is administered by inhalation through the Breezhaler® device. The speed of bronchodilation is similar to that with salbutamol (ie, about five minutes) and longer (ie, 24 hours) than that with traditional LABA, with the same 12-hour effect as salmeterol and formoterol, both of which require twice-daily administration. This is why indacaterol has been called the “ultra-LABA”. On the one hand, the fast onset of action provides immediate relief of symptoms, and on the other, its constant 24-hour bronchodilation provides “pharmacologic stenting” which facilitates lung emptying, thereby decreasing trapped gas and pulmonary hyperinflation. Once-daily administration of a fast and long-acting bronchodilator can improve patient adherence with therapy, which is known to be a major problem for many medical treatments. Dose-finding trials have shown that 75 μg is the minimum dose needed to achieve clinically important improvement. However, indacaterol 150 μg and 300 μg achieve an even greater improvement in lung function and patient-oriented outcomes. Further, these two doses of indacaterol significantly reduce pulmonary hyperinflation, thereby improving exercise tolerance and ability to perform day-to-day activities. It is more effective on lung volumes at the 300 μg dose than formoterol, and better than salmeterol and tiotropium at the 150 μg dose, at least in the acute setting. It is noteworthy that few studies document these results in patients with COPD and moderate airflow obstruction. These are exactly the kind of patients our research should be concentrating on, in view of the accelerated decay in forced expiratory volume in one second at this stage of the disease. Finally, all the relevant studies show that indacaterol is consistently well tolerated by patients with COPD at every stage, and that it has a high safety profile.

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“…In the treatment of COPD, once-daily administration is particularly attractive for patient drug compliance 26. In COPD, as for other chronic diseases, poor compliance is common and associated with increased rates of morbidity, health care expenditure, diminished quality of life, hospitalizations, and mortality 27…”

Section: Issue Of Adherencementioning

confidence: 99%

Role of indacaterol and the newer very long-acting β2-agonists in patients with stable COPD: a review

Ridolo¹,

Montagni²,

Olivieri³

et al. 2013

COPD

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Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting β2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting β2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting β2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting β2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far.

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Efficacy of indacaterol in the treatment of patients with COPD

Cited by 20 publications

References 32 publications

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β₂-Adrenoceptor Agonist

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β₂-Adrenoceptor Agonist

Indacaterol: a comprehensive review

Role of indacaterol and the newer very long-acting β2-agonists in patients with stable COPD: a review

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Efficacy of indacaterol in the treatment of patients with COPD

Cited by 20 publications

References 32 publications

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β2-Adrenoceptor Agonist

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β2-Adrenoceptor Agonist

Indacaterol: a comprehensive review

Role of indacaterol and the newer very long-acting &beta;2-agonists in patients with stable COPD: a review

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About

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β₂-Adrenoceptor Agonist

The In Vitro Pharmacology of GS-5759, A Novel Bifunctional Phosphodiesterase 4 Inhibitor and Long Acting β₂-Adrenoceptor Agonist

Role of indacaterol and the newer very long-acting β2-agonists in patients with stable COPD: a review