Phase III THARROS Trial to Evaluate Impact of Breztri Aerosphere on Cardiopulmonary Outcomes in COPD
THARROS trial investigators seek to provide first-of-its-kind evidence supporting a strategy of comprehensive cardiopulmonary risk reduction with a triple therapy in patients with chronic obstructive pulmonary disease.
Image credit: Crystal light | stock.adobe.com
AstraZeneca has announced plans to launch the Phase III THARROS trial to evaluate Breztri Aerosphere—a single-inhaler, fixed-dose, triple-combination therapy—in patients with chronic obstructive pulmonary disease (COPD) who have an elevated cardiopulmonary risk, regardless of prior exacerbation history.1 In addition, the company announced that the first patients have been dosed in the Phase III ATHLOS trial to compare the efficacy of Breztri Aerosphere with ICS/LABA budesonide/formoterol fumarate (BFF) or placebo on cardiopulmonary measures such as hyperinflation and exercise endurance time. Breztri Aerosphere was initially approved in July 2020 for the maintenance treatment of patients with COPD.2
“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 THARROS trial coordinating investigator Fernando Martinez, MD, MS, chief of the Division of Pulmonary and Critical Care Medicine at Weill Cornell Medicine and New York-Presbyterian Hospital, in a press release. “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, including for patients with no history of exacerbations, for whom no evidence currently exists.”1
Breztri Aerosphere combines budesonide, an inhaled corticosteroid; glycopyrrolate, an anticholinergic; and formoterol fumarate, a long-acting beta2-adrenergic agonist. In addition to the United States, the therapy has been approved to treat COPD in more than 50 countries worldwide and is currently under evaluation in Phase III trials to treat asthma.
Approximately 391 million individuals worldwide are affected by COPD, which increases the risk of adverse pulmonary and cardiovascular outcomes, including severe or fatal COPD exacerbations and cardiopulmonary risk. These risks are elevated following a single COPD exacerbation—which can persist for up to a year following the exacerbation—doubling the risk of a heart attack and increasing the risk of hospitalization and cardiopulmonary-related death.1
“Large outcomes trials have transformed the management of cardiovascular diseases by enhancing our understanding of the potentially broad impact of therapies targeting those diseases. Current evidence already supports a proactive treatment approach in COPD,” said David Berg MD, MPH, associate physician in Cardiovascular and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, in a press release. “Now THARROS is seeking to provide first-of-its-kind evidence to support a strategy of comprehensive cardiopulmonary risk reduction with a triple therapy.”1
The randomized, multi-center, double-blind, parallel-group THARROS trial will enroll approximately 5,000 COPD patients with cardiopulmonary risk, aged between 40 and 80 years. The trial’s novel composite endpoint will combine respiratory and cardiac outcomes, with a primary endpoint of time to first severe cardiac event, severe COPD exacerbation, or cardiopulmonary death.
The randomized, multi-center, double-blind, three-treatment, three-period, crossover ATHLOS trial is comparing the efficacy of Breztri Aerosphere vs. BFF or placebo on isotime inspiratory capacity and exercise endurance time in patients with COPD with exertional breathlessness following treatment with monotherapy or dual COPD maintenance therapy. Investigators will enroll 180 patients between 40 and 80 years of age.
“We have an important and urgent mission to eliminate COPD as a leading cause of death. 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, AstraZeneca executive vice president, BioPharmaceuticals R&D, said in a press release. “With the first-of-its-kind THARROS study, we aim to demonstrate the potential of triple therapy to address cardiopulmonary risk.”1
References
1. AstraZeneca announces initiation of THARROS – a Phase III clinical trial investigating the potential of BREZTRI to improve cardiopulmonary outcomes in people with COPD. AstraZeneca. News release. March 13, 2024. Accessed March 14, 2024. https://finance.yahoo.com/news/astrazeneca-announces-initiation-tharros-phase-110600738.html
2. Breztri Aerosphere approved in the US for the maintenance treatment of COPD. AstraZeneca. News release. July 24, 2020. Accessed March 14, 2024. https://www.astrazeneca-us.com/media/press-releases/2020/breztri-aerosphere-approved-in-the-us-for-the-maintenance-treatment-of-copd-07242020.html.
Merck Launches Phase III Trials of Once-Monthly Oral HIV PrEP Candidate MK-8527
July 14th 2025In the new EXPrESSIVE clinical trial program, Merck will evaluate MK-8527, a once-monthly, oral PrEP therapy, in populations at high risk of HIV-1 infection, including adolescent girls and women in sub-Saharan Africa.
Unifying Industry to Better Understand GCP Guidance
May 7th 2025In this episode of the Applied Clinical Trials Podcast, David Nickerson, head of clinical quality management at EMD Serono; and Arlene Lee, director of product management, data quality & risk management solutions at Medidata, discuss the newest ICH E6(R3) GCP guidelines as well as how TransCelerate and ACRO have partnered to help stakeholders better acclimate to these guidelines.
Baxdrostat Shows Significant Blood Pressure Reduction in Phase III BaxHTN Trial
July 14th 2025In the BaxHTN Phase III study, AstraZeneca’s baxdrostat demonstrated statistically significant and clinically meaningful reductions in systolic blood pressure in patients with uncontrolled or treatment-resistant hypertension.
New FDA Initiative Reveals Common Reasons for Drug Application Rejection
July 11th 2025By publishing more than 200 complete response letters, the FDA is offering new visibility into the issues that most often delay drug approvals, including safety concerns, trial design flaws, and manufacturing gaps.
Arcus’ Quemliclustat Earns Orphan Drug Designation as Phase III Pancreatic Cancer Trial Advances
July 11th 2025The FDA has granted orphan status to Arcus Biosciences’ CD73 inhibitor quemliclustat for metastatic pancreatic cancer, as the global PRISM-1 Phase III trial nears full enrollment following promising survival data from ARC-8.
