FDA Approves Triple Combination Therapy for Maintenance Treatment of COPD

July 28, 2020

Approval was based on trials that reported significantly reduced exacerbation rates compared with dual-combination therapies.

The FDA has approved budesonide/glycopyrrolate/formoterol fumarate (BGD MDI) (Breztri Aerosphere, AstraZeneca), for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). 1

The approval of the triple combination therapy cited favorable results produced by the phase 3 ETHOS trial, published in The New England Journal of Medicine, as well as the phase 3 KRONOS trial, which was published in The Lancet Respiratory Medicine. 1

According to investigators, though triple fixed-dose therapies of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting 2 -agonist (LABA) for COPD have been researched at single dose levels, studies focused on 2 dose levels have been missing from the reservoir of COPD research. 2

COPD causes airflow obstruction in the lungs that causes significant breathing difficulty for patients, affecting approximately 384 million individuals, and is the third leading cause of death around the world. Even isolated flares in COPD often lead to substantial declines in lung function, as well as reduced life expectancy and increase mortality risk. Reducing COPD exacerbations remain critical treatment goals.2

The phase 3, 52-week, randomized controlled trial (RCT) ETHOS trial, funded by AstraZeneca, included 8509 patients with COPD and monitored rates of moderate or severe exacerbations. 2

Investigators reported annual rates to be 1.08 in the 320-g-budensonide triple-therapy group (2137 patients); 1.07 in the 160--budesonide triple-therapy group (2121 patients); 1.42 in the glycopyrrolate-formoterol group (2120 patients); and 1.24 in the budesonide-formoterol group (2131 patients). 2 The rate was 25% lower with 320-g-budesonide triple therapy than with glycopyrrolate-formoterol or budesonide-formoterol, which expressed a rate that was 13% lower. Similarly, the rate was 25% lower with 160-g-budesonide triple therapy than with glycopyrrolate-formoterol, which decreased rates by 14%.2

Adverse events (AEs) were similar across treatment groups, according to investigators, and included confirmed pneumonia, which was present in between 3.5% to 4.5% of patients that were administered inhaled glucocorticoid; pneumonia was present in 2.3% of patients in the glycopyrrolate-formoterol group. 2

The double-blind, parallel-group, multicenter phase 3 RCT KRONOS incorporated 3057 patients from 215 sites who were randomized to receive either BGF MDI, glycopyrrolate/formoterol fumarate metered-dose inhaler (GFF MDI), or open-label budesonide/formoterol fumarate dry-powder inhaler (BUD/FORM DPI).3

The KRONOS study found BGF to be effective and well tolerated by patients with COPD in the trial, and demonstrated that the triple combination therapy could be more appropriate than the mentioned dual therapies for patients with moderate to very severe COPD. 3

Mene Pangalos, executive vice president, BioPharmaceuticals R&D, said, “BREZTRI AEROSPHERE has demonstrated a strong clinical profile compared with dual-combination therapies and offers a meaningful new treatment option for patients. Chronic obstructive pulmonary disease is a debilitating progressive condition and the fourth leading cause of death in the US. We look forward to discussing all-cause mortality data from the BREZTRI AEROSPHERE ETHOS trial with health authorities.”

References:

  1. BREZTRI AEROSPHERE approved in the US for the maintenance treatment of COPD. News Release. AstraZeneca; July 24, 2020. Accessed July 28, 2020. https://www.astrazeneca-us.com/media/press-releases/2020/breztri-aerosphere-approved-in-the-us-for-the-maintenance-treatment-of-copd-07242020.html.
  2. Rabe KF, Martinez FJ, Ferguson GT, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. The New England Journal of Medicine; 2020. doi: 10.1056/NEJMoa1916046.
  3. Ferguson GT, Rabe KF, Martinez FJ, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. The Lancet; 2018. doi: https://doi.org/10.1016/S2213-2600(18)30327-8.