AstraZeneca's Triple-Combination COPD Inhaler Breztri Aerosphere Approved in China Ahead of US and EU

December 23, 2019, Shanghai, China— AstraZeneca announced today that the China National Medical Products Administration has officially approved budesonide/glycopyrronium/formoterol pressurized metered-dose inhaler for maintenance treatment in patients with chronic obstructive pulmonary disease (COPD). As an innovative triple-combination inhaled therapy for COPD, this approval in China precedes those in Europe and the United States, making China the second country globally to approve this medication.

Budesonide/Glycopyrronium/Formoterol Fumarate Inhalation Aerosol utilizes innovative co-suspension delivery technology to jointly deliver three active ingredients: budesonide (an inhaled corticosteroid, ICS), glycopyrronium bromide (a long-acting muscarinic antagonist, LAMA), and formoterol fumarate (a long-acting β2-agonist, LABA), providing an important therapeutic option for patients with stable chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases in China. The latest epidemiological survey data from 2018 show that the total number of COPD patients in China is nearly 100 million, with one in every seven people aged 40 and above affected by the disease. The "Opinions of the State Council on Implementing the Healthy China Action" also pointed out that China will implement actions for the prevention and control of chronic respiratory diseases, including COPD. Budesonide/Glycopyrronium/Formoterol fumarate dihydrate metered-dose inhaler entered the priority review channel of the National Medical Products Administration in January 2019. Its approval in China prior to Europe and the United States reflects the severe situation faced in the treatment of COPD in China and serves as another example of China’s pharmaceutical regulatory review prioritizing patient needs.

Patients with chronic obstructive pulmonary disease (COPD) often experience sudden worsening of symptoms, leading to hospital visits or even hospitalization, known as acute exacerbations of COPD (AECOPD). According to statistics, the median number of acute exacerbations per year among COPD patients in China is as high as three. Acute exacerbations can lead to rapid disease progression, cause irreversible damage to lung function, and significantly increase the risk of mortality. Data shows that within 3.6 years after discharge following a patient’s first acute exacerbation, the all-cause mortality rate rises to 50%, reaching as high as 75% within 7.7 years.

Compared with dual therapy, budesonide/glycopyrronium/formoterol fumarate triple inhalation therapy delivers multiple benefits for patients with chronic obstructive pulmonary disease (COPD). Results from the KRONOS study, published in The Lancet Respiratory Medicine, demonstrated that, compared with dual bronchodilator therapy, the triple therapy regimen significantly reduced the rate of moderate-to-severe exacerbations by 52% and prolonged the time to first moderate-to-severe exacerbation. Furthermore, the medication exhibited a rapid onset of action, provided sustained and significant improvements in lung function, and demonstrated a favorable safety profile.

In China, the majority of patients with chronic obstructive pulmonary disease (COPD) are elderly¹. The use of inhaled medications by these patients is often limited by certain factors, such as reduced inspiratory flow rate, thereby affecting therapeutic efficacy. Budesonide/Glycopyrronium/Formoterol pressurized metered-dose inhaler (pMDI) is currently the only triple therapy available in China that utilizes a pMDI device. Its innovative Aerosphere® device is an active aerosol-generating system, ensuring that the patient’s inspiratory flow rate does not affect aerosol characteristics. Furthermore, the Aerosphere® device employs innovative co-suspension delivery technology, utilizing lightweight porous phospholipid carriers that can adsorb drug crystals of three different densities. This ensures consistent active pharmaceutical ingredient content and enables uniform delivery of the medication to both large and small airways. In COPD patients, the pulmonary deposition rate of drugs carried by these phospholipid particles can reach 48%*.

Academician Wang Chen, Director of the National Clinical Research Center for Respiratory Diseases, Director of the Department of Respiratory Medicine at China-Japan Friendship Hospital, and Lead Investigator for the KRONOS Phase III Study in China, stated: “Reducing the disease burden of chronic obstructive pulmonary disease (COPD) is a priority issue in China’s public health sector. The KRONOS study demonstrated that, compared with dual therapy, budesonide/glycopyrronium/formoterol pressurized metered-dose inhaler can rapidly and sustainably improve lung function and reduce the risk of exacerbations in patients with moderate to severe COPD. Triple therapy will play a very important role in addressing the challenges of COPD in China, particularly acute exacerbations.”

Mr. Wang Lei, Global Vice President and President of International Business and China at AstraZeneca, stated, “In China, chronic obstructive pulmonary disease (COPD) is one of the leading chronic diseases causing mortality and is a key respiratory chronic condition highlighted in the Healthy China 2030 Planning Outline. The budesonide/glycopyrronium/formoterol triple therapy inhalation regimen provides an important treatment option for patients with COPD. We look forward to innovative medicines and devices delivering effective disease control for COPD patients and reducing the threats posed by acute exacerbations. The earlier launch of budesonide/glycopyrronium/formoterol pressurized metered-dose inhaler in China compared to Europe and the United States underscores AstraZeneca’s persistent patient-centric approach and its commitment to accelerating the availability of innovative medicines in China, reflecting the company’s determination to support the Healthy China 2030 initiative.”

About Budesonide/Glycopyrronium/Formoterol Inhalation Aerosol

Budesonide/Glycopyrronium/Formoterol Fumarate Inhalation Aerosol is a fixed-dose triple-combination inhalation product that utilizes an innovative device to co-deliver three active ingredients: budesonide (an inhaled corticosteroid, ICS), glycopyrronium (a long-acting muscarinic antagonist, LAMA), and formoterol fumarate (a long-acting β2-agonist, LABA). It provides an important therapeutic option for appropriate patients with chronic obstructive pulmonary disease (COPD) and offers a convenient and innovative mode of administration. In January 2019, Budesonide/Glycopyrronium/Formoterol Fumarate Inhalation Aerosol was granted priority review status. In December 2019, the National Medical Products Administration of China formally approved it for the maintenance treatment of patients with COPD.

Budesonide/Glycopyrronium/Formoterol Inhalation Aerosol, featuring the innovative Lichang device and utilizing co-suspension drug delivery technology, enables the medication to reach both large and small airways of the lungs, achieving high pulmonary deposition rates. Meanwhile, each actuation delivers a uniform and stable dose, ensuring accurate dosing from the first to the last inhalation.

About KRONOS

KRONOS was a randomized, double-blind, parallel-group, 24-week, multiple-dose, international, multicenter clinical trial designed to evaluate the efficacy and safety of triple therapy with budesonide/glycopyrronium/formoterol fumarate in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD). The study results were published in *The Lancet Respiratory Medicine* in 2018⁵.

On COPD and Acute Exacerbations of COPD

Chronic obstructive pulmonary disease (COPD) in China is characterized by the “four highs”: high prevalence, high disability rate, high mortality rate, and high disease burden. The latest epidemiological survey data show that the prevalence of COPD among individuals aged 40 years and older in China is 13.7%, with the number of patients approaching 100 million. According to World Health Organization statistics, China’s COPD mortality rate ranks highest globally, making it the third leading cause of death among residents. The overall disease burden of COPD has risen to the second highest among all diseases in China, exceeding the global average. Acute exacerbations of COPD are a manifestation of rapid disease deterioration; these episodes are highly detrimental to patients, causing irreversible lung function decline and significantly increasing the risk of mortality.

About AstraZeneca China

Since entering China in 1993, AstraZeneca has adhered to a science-led approach and prioritized innovation to meet the country’s growing health needs, fulfilling its ambitious vision of “pioneering innovation, benefiting patients, and becoming China’s most trusted healthcare partner.” Headquartered in Shanghai, AstraZeneca employs approximately 13,000 people across China. The company has established manufacturing bases in Wuxi and Taizhou, Jiangsu Province, and set up its China logistics center in Wuxi. In China, AstraZeneca focuses primarily on therapeutic areas with the most urgent patient needs, including respiratory, cardiovascular, metabolic, oncology, gastrointestinal, and renal diseases. In 2017, the China Health IoT Innovation Center was launched in Wuxi to explore innovative Internet of Things (IoT)-enabled integrated solutions for whole-disease-course management. In the same year, AstraZeneca formed a joint venture with SDIC Innovation to establish Dizal (Jiangsu) Pharmaceutical Co., Ltd., accelerating the local research and development of new drugs. In 2019, AstraZeneca announced a collaboration with the Wuxi Municipal Government and Wuxi High-Tech District to co-establish the Wuxi International Life Science Innovation Park, pooling global expertise to benefit patients in China.

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