'Breztri' reimb adds long-term prognostic management option for COPD

The diagnosis rate of COPD in South Korea is 2.8%…disease burden among elderly population remains

Improvements in lung function and quality of life…has provided clinical evidence for triple therapy

In the treatment of chronic obstructive pulmonary disease (COPD), the importance of long-term prognostic management, focusing on reducing the risk of acute exacerbations and death beyond simple management, is growing.

In particular, it is pointed out that early diagnosis and active prevention of exacerbations are necessary for COPD, given the low diagnostic rate and the high prevalence of comorbidities such as cardiovascular disease among elderly patients in South Korea. Related to this, the single-inhaler triple therapy 'Breztri Aerosphere' has entered the National Health Insurance reimbursement sphere and is expected to be used as a treatment option.

AstraZeneca Korea held a press conference at the President Hotel in Seoul on the 1st to commemorate the reimbursement listing of Breztri Aerosphere, introducing the domestic COPD disease burden, treatment landscape, and key clinical results.

Breztri is a high-dose inhaled corticosteroid (ICS) / long-acting muscarinic antagonist (LAMA) / long-acting beta2-agonist (LABA) triple therapy that combines budesonide, glycopyrronium, and formoterol in a single inhaler. It is used as a maintenance treatment in adults with moderate to severe COPD that is not adequately controlled by existing ICS/LABA or LABA/LAMA dual therapies.

The therapy was added to the reimbursement list this past September, approximately five years after receiving domestic approval in November 2021.

Low diagnostic rates and recurrent exacerbations... COPD management gaps remain

Professor Yong Il Hwang of the Division of Pulmonary, Allergy and Critical Care Medicine at Hallym University Sacred Heart Hospital

The biggest challenge for domestic COPD is the failure to identify patients promptly. Because lung function decline often manifests as symptoms only after a considerable period of progression, there is a significant gap between the actual prevalence and the number of patients diagnosed and treated at medical institutions.

Professor Yong Il Hwang of the Division of Pulmonary, Allergy and Critical Care Medicine at Hallym University Sacred Heart Hospital emphasized that COPD should not be viewed merely as a simple respiratory disease, especially in the domestic environment where the population is aging rapidly.

This is because comorbidities such as cardiovascular disease are common, and recurrent acute exacerbations can impact the subsequent prognosis.

COPD is a chronic disease characterized by persistent airflow limitation and respiratory symptoms due to structural abnormalities in the airways and alveoli. While smoking is known as a primary risk factor, the importance of non-smoking factors, such as various environmental and occupational exposures, is also being emphasized recently.

As the disease progresses, lung function declines, symptoms such as dyspnea and coughing worsen, and acute exacerbations can recur. Particularly in the elderly population, multiple comorbidities, including cardiovascular disease, often present simultaneously, further increasing the disease burden.

Professor Hwang stated, "COPD is a common disease, but many patients remain undiagnosed," adding, "In the National Health and Nutrition Examination Survey, among those who met the criteria for COPD through pulmonary function tests, the proportion who were aware they had actually been diagnosed with COPD was a mere 2.8%."

The fact that COPD predominantly affects the elderly was also cited as a factor that will increase the future disease burden. As the domestic population ages rapidly, the burden of COPD patients and associated healthcare costs is likely to persist.

In reality, the socioeconomic burden of domestic COPD is at a substantial level. In a Korean study, Professor Hwang reported that the socioeconomic costs of COPD and its comorbidities amount to approximately 1.4 trillion won annually.

A particularly important metric in treatment is 'acute exacerbations.' When an acute exacerbation occurs, lung function, physical activity, and quality of life deteriorate, and the likelihood of subsequent exacerbations also increases. It can also impact the risk of cardiovascular events and death.

Professor Hwang emphasized, "Patients who have experienced an exacerbation once are at a higher risk of exacerbating again," and "Ultimately, in COPD treatment, it is important to prevent the first exacerbation as much as possible."

Recent global guidelines also reflect this direction. The GOLD guidelines include not only symptom improvement but also reduced acute exacerbation and mortality risks as treatment goals in COPD, and suggest triple therapy with an ICS, taking into account the patient's history of exacerbations and blood eosinophil counts.

Professor Hwang noted, "In the past, there was a tendency to delay the use of triple therapy due to concerns about ICS side effects, but this can lead to patients experiencing recurrent exacerbations while being delayed from necessary treatments," adding, "It is crucial to screen patients in need and treat them at the appropriate time."

Triple therapy, evidence accumulated for reducing exacerbation and mortality risks

Professor Sang Hyuk Kim of the Division of Pulmonary, Allergy and Critical Care Medicine at Korea University Guro Hospital

Professor Sang Hyuk Kim of the Division of Pulmonary, Allergy and Critical Care Medicine at Korea University Guro Hospital introduced the clinical evidence for Breztri.

Representative studies include the phase 3 clinical trials ETHOS and KRONOS.

In the ETHOS study, conducted over 52 weeks and involving approximately 8,500 patients with moderate-to-severe COPD, Breztri reduced the annual rate of moderate or severe COPD acute exacerbations by 24% compared with LAMA/LABA dual therapy. It also demonstrated a 13% reduction compared to ICS/LABA.

In a pre-specified ETHOS analysis, Breztri was also associated with a reduced risk of all-cause mortality compared with LAMA/LABA. In a post-hoc analysis, the risk of severe cardiopulmonary events was also lower than with LAMA/LABA.

Professor Kim explained, "While COPD patients often die from respiratory causes as the disease progresses to severe stages, cardiovascular disease can be a significant cause of death in relatively milder stages," adding, "This is why cardiopulmonary events must be managed together in COPD."

The KRONOS study included over 74% of patients with no history of exacerbations in the previous year. In this study, Breztri also lowered the annual rate of moderate or severe COPD exacerbations by 52% compared with LAMA/LABA.

Differences were also confirmed in lung function. In KRONOS, Breztri improved the 24-week FEV1 AUC0-4 by 104 mL compared to ICS/LABA.

Professor Kim stated, "Breztri has confirmed its efficacy across multiple metrics, from improving lung function to enhancing symptoms and quality of life, and reducing exacerbations," noting, "Rather than escalating treatment after exacerbations worsen, it is important to initiate appropriate treatment in patients who need it."

pMDI delivery method tailored for patients with low inspiratory flow

Breztri's inhaler delivery method was also presented as a key feature.

Breztri uses a pressurized metered-dose inhaler (pMDI) rather than a dry powder inhaler (DPI), which draws powder-form medication using the patient's inspiratory effort. The explanation is that because the medication is sprayed at a consistent pressure, patients with reduced inspiratory flow can still use it.

Professor Kim introduced findings from a study on domestic COPD patients showing that about one-fifth of patients using DPIs failed to generate sufficient inspiratory flow rates. This suggests that inspiratory effort may be inadequate in certain patients, such as the elderly or women.

However, because pMDIs also require coordinating actuation timing with inhalation, patients with impaired hand dexterity or cognitive function may have difficulty using them.

Breztri uses 'Aerosphere' technology for drug delivery. This technology uniformly disperses the three active ingredients by binding the medication to porous, low-density phospholipid particles.

Professor Kim also introduced a CT-based computational fluid dynamics simulation study. He explained that comparing the lung deposition patterns of Breztri with other triple-therapy inhalers showed Breztri had relatively lower oropharyngeal deposition and higher overall lung deposition.

Professor Kim clarified that this study did not directly compare actual patient clinical outcomes.

Professor Kim stated, "In the patient breathing patterns used in the simulation, Breztri demonstrated high deposition across the entire lung due to various engineering characteristics," adding, "Further research is needed in the future to understand how these deposition properties translate into actual clinical improvements for patients."