Phase 3 trial of Breztri in easing cardiopulmonary problems opens

THARROS study enrolling up to 5,000 at-risk patients at sites worldwide

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by Andrea Lobo |

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A Phase 3 clinical trial assessing the potential of triple-combination Breztri Aerosphere (budesonide/glycopyrronium/formoterol fumarate) to improve cardiopulmonary outcomes in people with chronic obstructive pulmonary disease (COPD) is opening at sites worldwide, AstraZeneca, which markets the inhaled therapy, announced.

The THARROS study (NCT06283966) is expected to enroll up to 5,000 COPD patients, ages 40 to 80, with a risk of cardiopulmonary complications at more than 650 centers in the U.S., Canada, and countries in Europe, South America, and Asia.

Participants will be randomly assigned to receive either Breztri Aerosphere or to AstraZeneca’s dual-combination Bevespi Aerosphere (glycopyrronium/formoterol fumarate) for up to three years.

“Even moderate COPD exacerbations are associated with increased risks of further lung events, severe cardiovascular complications and have been shown to contribute to patients dying,” Sharon Barr, PhD, AstraZeneca’s executive vice president and head of BioPharmaceuticals R&D, said in a company press release.

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Fernando Martinez, MD, the trial’s international coordinating investigator, said that “if positive, the THARROS trial will provide critical evidence about the potential of single inhaler, triple combination therapy to reduce severe cardiopulmonary events and further advance treatment goals in COPD.

Eligible study patients include those considered at risk but “with no history of exacerbations,” Martinez said.

COPD is a chronic inflammatory disease affecting the lungs, in which the airways become blocked, causing such disease symptoms such as cough with mucus, wheezing, and shortness of breath. Some patients also experience exacerbations, or sudden episodes of symptom worsening, that may persist for several days.

Breztri Aerosphere, formerly known as PT010, is a triple-combination inhaled therapy designed to alleviate symptoms and reduce exacerbation frequency. It contains glycopyrronium and formoterol fumarate, both working to help to widen the airways, as well as the anti-inflammatory corticosteroid budesonide.

Breztri Aerosphere was approved in the U.S. as a maintenance treatment for people with COPD in 2020. It is also approved for COPD in the European Union, China, and Japan.

These regulatory decisions were based on data from two Phase 3 clinical trials: ETHOS (NCT02465567) and KRONOS (NCT02497001).

The ETHOS study showed that Breztri Aerosphere significantly reduced the frequency of moderate or severe COPD exacerbations, compared with the dual-combination therapies Bevespi Aerosphere and Symbicort (budesonide/formoterol fumarate).

The earlier KRONOS trial showed that about six months of treatment with Breztri Aerosphere reduced exacerbation frequency and improved lung function relative to the dual-combination maintenance therapies.

In both trials, the triple combination treatment’s safety profile was similar to that of the dual-combination therapies used for comparison.

Trial will assess cardiopulmonary outcomes in patients given Breztri Aerosphere

AstraZeneca last year presented data from a real-world registry study, called EROS, showing that treatment with Breztri Aerosphere shortly after a moderate or severe COPD exacerbation can lower the risk of further such flares.

In THARROS, the potential of Breztri Aerosphere to reduce severe cardiopulmonary events in COPD patients considered at cardiopulmonary risk will be evaluated using a novel combination measure of respiratory and heart-related, or cardiac, outcomes.

Its primary goal is assessing the time to a first severe cardiac or COPD event over up to three years of treatment. Secondary coals include time to a first severe COPD exacerbation, severe cardiac event, or death from respiratory and cardiac causes, and the rate of moderate or severe COPD exacerbations. The study is expected to be completed in 2028.

“The 2024 GOLD Report highlights the treatment effect of non-pharmacologic interventions and inhaled triple combination therapies on mortality. The Report calls for a more proactive therapeutic approach to improve outcomes in COPD,” said Martinez, who is the chief of pulmonary and critical care medicine at New York-Presbyterian/Weill Cornell Medical Center.

“Now THARROS is seeking to provide first-of-its-kind evidence to support a strategy of comprehensive cardiopulmonary risk reduction with a triple therapy,” said David Berg, MD, a physician in cardiovascular and critical care medicine at Brigham and Women’s Hospital in Massachusetts.

Separate trial into Breztri Aerosphere and exercise endurance also enrolling

The company also announced the start of dosing in the Phase 3 ATHLOS trial (NCT06067828), which is enrolling up to 180 COPD patients, ages 40-80, with shortness of breath during exercise despite treatment with an inhaled monotherapy or dual-combination maintenance therapy.

Patients randomly are being assigned to either Breztri Aerosphere, Symbicort, or a placebo. The trial is assessing the treatment’s effect on integrated cardiopulmonary parameters, including lung hyperinflation (overinflated lungs) and exercise endurance, which are associated with health status and survival in people with COPD.

The FDA issued a warning letter to AstraZeneca last year for making claims about Breztri Aerosphere’s effectiveness that it considered false or misleading, because they were not supported by clinical evidence. These include the therapy’s ability to reduce the risk of severe exacerbations as well as the risk of death from any cause.