Long-acting bronchodilators in COPD: where are we now and where are we going?

Cazzola, Mario; Page, Clive

doi:10.1183/20734735.014813

Cited by 44 publications

(30 citation statements)

References 63 publications

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“…Bronchodilators, particularly long-acting muscarinic antagonists (LAMAs) and long-acting b 2 -agonists (LABAs), have become the mainstay of pharmacological therapy for chronic obstructive pulmonary disease (COPD) [1][2][3]. Despite the well-demonstrated utility of LABAs [4][5][6][7] and LAMAs [8][9][10][11] as maintenance therapy, a high number of patients with moderate or severe COPD receiving LABA or LAMA monotherapy can fail to achieve adequate control of symptoms [12].…”

Section: Introductionmentioning

confidence: 99%

A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

Sion

Huisman²,

Punekar

et al. 2017

Pulm Ther

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Section: Introductionmentioning

confidence: 99%

A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

Sion

Huisman²,

Punekar

et al. 2017

Pulm Ther

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“…Inhaled long-acting bronchodilators are used for the treatment of patients with moderate and more severe COPD (14), and now, agents are available for once-daily administration. Indacaterol is an inhaled, once-daily, ultra-long-acting β2-agonist (15).…”

Section: Introductionmentioning

confidence: 99%

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

et al. 2017

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Abstract.Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

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“…However, although this minimizes the risk of clinical failure and losing financial investments from a clinical trial risk perspective, the launch of these ‘me too' products based on well-known mechanisms may in turn encounter significant commercial challenges in the marketplace. Overall, COPD has traditionally been an area where manufacturers have looked to improve on drugs with well-known mechanisms of action and where new therapies may only be slight improvements over their predecessors [31,32]. Thus, products not first to market in their respective drug classes may encounter significant commercial hurdles in differentiating from competitors or changing clinical practice in an already crowded marketplace.…”

Section: Discussionmentioning

confidence: 99%

Clinical Trial Risk in Chronic Obstructive Pulmonary Disease: The Effects of Drug Class and Inclusion Criteria

Tam¹,

Parker²,

Anastasopulos³

et al. 2015

Respiration

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Background: This study analyzed the risk of clinical trial failure in chronic obstructive pulmonary disease (COPD) drug development between 1998 and 2015. We investigated elements that influenced clinical trial risk and factors that could improve outcomes during development. Objectives: This study aims to quantify clinical trial risk for drug development in COPD and factors that affect clinical trial risk. Methods: Drugs that commenced their phase I testing in this indication from 1998 onwards were retrieved from http://www.clinicaltrials.gov. Compounds investigated had to have an endpoint relevant to the treatment of COPD and be sponsored by the pharmaceutical industry. These compounds were then analyzed based on their mechanism of action and trial inclusion criteria. Results: A total of 766 trials met our screening criteria representing 116 drugs. Of these, 9 gained approval by the US FDA during our study period. The cumulative success rate for clinical development in COPD was 13.4%. Combination therapies of long-acting β-adrenoceptor agonists (LABA)/long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)/LABA had the highest success rates at 80 and 50%, respectively. The risk-adjusted cost for drug development in COPD was USD 532.4 million. Conclusions: A 13.4% success rate in COPD implies that less than 1 in 7 compounds enrolled into clinical testing would gain FDA approval. LABA/LAMA and ICS/LABA therapies had multiple fold increases in the success rate compared to other drug classes and sizably decreased the risk-adjusted cost of drug development. Moving forward, combination therapies may offer the lowest risk of clinical failure in COPD drug development.

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Long-acting bronchodilators in COPD: where are we now and where are we going?

Cited by 44 publications

References 63 publications

A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

Clinical Trial Risk in Chronic Obstructive Pulmonary Disease: The Effects of Drug Class and Inclusion Criteria

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