AstraZeneca (LON:AZN) today announced that budesonide/glycopyrronium/formoterol fumarate has been approved in China for the maintenance treatment of chronic obstructive pulmonary disease (COPD).
This is the first approval by the National Medical Products Administration for a triple-combination therapy in a pressurised metered-dose inhaler (pMDI), which uses the innovative Aerosphere delivery technology.
The approval follows a priority review and is based on results from the Phase III KRONOS trial in which PT010 demonstrated a statistically significant improvement in trough forced expiratory volume in one second (FEV1), the primary endpoint for China, compared with dual-combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate) and PT009 (budesonide/formoterol fumarate).
The safety and tolerability of PT010 were consistent with the known profiles of the dual comparators. Data from the KRONOS trial were published in The Lancet Respiratory Medicine in October 2018.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Chronic obstructive pulmonary disease affects almost 100 million people in China, and is a leading cause of morbidity and mortality. With this approval, we are now able to provide a powerful new triple-combination therapy to patients for whom new treatments are critically needed. Our triple-combination therapy is administered in a pressurised metered-dose inhaler, an important device option for clinicians and patients in China.”
Professor Wang Chen, Director of China National Clinical Research Centre for Respiratory Diseases, Director of the Centre for Respiratory Disease at China-Japan Friendship Hospital, and China National Lead Investigator of the KRONOS trial, said: “Addressing the burden of chronic obstructive pulmonary disease in China is a public health priority and triple-combination therapy will play an important role in helping patients manage their disease. In the KRONOS trial, budesonide/glycopyrronium/formoterol fumarate provided rapid and sustained lung function improvements in patients with moderate-to-very-severe disease.”
Budesonide/glycopyrronium/formoterol fumarate was approved in Japan in June 2019 as Breztri Aerosphere, a triple-combination therapy to relieve symptoms of COPD. The medicine is also under regulatory review in the US and EU, under the name PT010.
ATHENA is AstraZeneca’s Phase III global clinical trial programme for PT010, including 11 completed trials with more than 15,500 patients.4,5,6,7 The four key trials are ETHOS, KRONOS, TELOS and SOPHOS.4,5,6,7 The ETHOS and KRONOS trials assessed the efficacy and safety of PT010.4,5 The TELOS and SOPHOS trials characterised PT009 and substantiated it as an active comparator in the PT010 clinical trial programme.6,7
In the KRONOS Phase III randomised, double-blinded, parallel-group, 24-week, chronic-dosing, multi-centre trial, PT010 met six of seven lung function primary endpoints versus dual-combination therapies Bevespi Aerosphere, Symbicort Turbuhaler (budesonide/formoterol fumarate) and PT009 in patients with moderate-to-very-severe COPD, in a patient population without a requirement for an exacerbation in the previous year.5 PT009 also met two non-inferiority endpoints to support its qualification as an active comparator. As published in The Lancet Respiratory Medicine, in a key secondary endpoint, PT010 showed a statistically significant 52% reduction in the rate of moderate or severe COPD exacerbations compared with Bevespi Aerosphere.5
In the ETHOS Phase III randomised, double-blinded, multi-centre, parallel-group, 52-week trial, PT010 demonstrated a statistically significant reduction in the rate of moderate or severe exacerbations compared with dual-combination therapies Bevespi Aerosphere and PT009 in patients with moderate-to-very-severe COPD and a history of exacerbation(s) in the previous year.4 Full trial design details are published in Respiratory Medicine.8 AstraZeneca announced results from the Phase III ETHOS trial in August 2019.9
Bevespi Aerosphere is a fixed-dose dual bronchodilator in a pMDI, combining glycopyrronium, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta2-agonist (LABA). Symbicort Turbuhaler is a single inhaler containing budesonide, an inhaled corticosteroid (ICS), and formoterol, a LABA. PT009 is a single inhaler, fixed-dose dual-combination therapy of budesonide, an ICS, and formoterol fumarate, a LABA.