Breztri Aerosphere is a triple combination drug of budesonide, glycopyrronium and formoterol fumarate.
AstraZeneca’s Phase III ETHOS clinical trial for Breztri Aerosphere, formerly PT010, showed statistically significant improvements in moderate to very severe chronic obstructive pulmonary disease (COPD).
Breztri Aerosphere is a triple combination drug of budesonide, glycopyrronium and formoterol fumarate (BGF). Glycopyrronium is a long-acting muscarinic antagonist (LAMA). Formoterol fumarate is a long-acting beta2-agonist (LABA). Budesonide is an inhaled corticosteroid.
The ETHOS trial compared Breztri Aerosphere in several doses in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous years. The trial looked at more than 8,500 patients. It was compared to what the company dubbed Bevespi Aerosphere, a fixed-dose dual bronchodilator containing glycopyrronium and formoterol, which was used as a comparator for Breztri Aerosphere clinical trials.
The triple-combo drug hit the mark at the standard dose. Even at half the budesonide dose, Breztri Aerosphere showed a statistically significant decrease in the rate of moderate or severe exacerbations compared with Bevespi Aerosphere and PT009. PT009 is the Symbicort Turbuhaler, which is budesonide and formoterol fumarate.
“Exacerbations are devastating events for patients and can lead to a permanent loss of lung function,” stated Mene Pangalos, executive vice president, BioPharmaceuticals R&D for AstraZeneca. “The Phase III ETHOS trial builds on the Phase III KRONOS data which together show Breztri Aerosphere’s ability to reduce exacerbation risk in a broad range of patients with COPD, irrespective of whether they have had an exacerbation in the previous twelve months. We look forward to sharing these results with health authorities as soon as possible.”
The safety and tolerability of Breztri Aerosphere were consistent with what is known about the dual comparators. During the trial, the various combination therapies were administered by way of a pressurized metered-dose inhaler using the Aerosphere delivery technology.
Trial details were published in the journal Respiratory Medicine. The trial looked at two doses of single inhaler triple therapy, budesonide, glycopyrrolate and formoterol fumarate (BGF), and compared it to a combination of glycopyrrolate and formoterol fumarate (GFF) and to a formulation of budesonide and formoterol fumarate (BFF).
Outcomes included the rate of moderate/severe COPD exacerbations, which was the primary endpoint, severe COPD exacerbations, symptoms, quality of life, and all-cause mortality. Sub-studies are being conducted to assess lung function and cardiovascular safety.
Between June 2015 and July 2018, 16,044 patients were screened and 8,572 were randomized.
Breztri Aerosphere is currently approved in Japan. Marketing applications are being reviewed in China, the U.S. and European Union.
“The Phase III ETHOS trial results are exciting and demonstrate that Breztri Aerosphere significantly reduces the rate of exacerbations,” stated Klaus Rabe, professor of Pulmonary Medicine at the University of Kiel, director of the Department of Pneumology at Clinic Grosshansdorf, Germany, and lead investigator of the ETHOS trial. “This is also the first time we have seen the benefit of fixed-dose triple-combination therapy at two inhaled corticosteroid doses, which could transform treatment practice by allowing physicians to select the optimal dose for individual patients.”
ETHOS is part of AstraZeneca’s ATHENA clinical trial program for Breztri Aerosphere, which has more than 15,500 patients around the world in 11 clinical trials. The four primary trials are ETHOS, KRONOS, TELOS and SOPHOS.
