The company has announced the top-line results from the Phase III KRONOS trial, which showed PT010 (budesonide/glycopyrronium/formoterol fumarate 320/14.4/9.6µg, using Aerosphere Delivery Technology, in a pressurised metered-dose inhaler or pMDI) demonstrated a statistically significant improvement compared with dual combination therapies in six out of seven lung function primary endpoints based on forced expiratory volume in one second (FEV1) assessments in patients with moderate to very severe COPD.
In total, eight of the nine primary endpoints in the KRONOS trial were met, including two non-inferiority endpoints to qualify PT009, one of the comparators.
KRONOS is a randomised, double-blind, parallel-group, 24-week, chronic-dosing, multi-centre trial to assess the efficacy and safety of PT010. The trial compared PT010 to Bevespi Aerosphere (glycopyrronium/formoterol fumarate 14.4/9.6µg pMDI), Symbicort Turbuhaler (budesonide/formoterol fumarate 400/12µg) and PT009 (budesonide/formoterol fumarate 320/9.6µg using Aerosphere Delivery Technology in a pMDI, being characterised to qualify as a relevant comparator in clinical trials for PT010).1 Patients were given two inhalations twice a day of PT010, PT009, Bevespi Aerosphere or Symbicort Turbuhaler.
Dr. Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: “We are encouraged by the results of the KRONOS trial that has demonstrated PT010’s efficacy in improving lung function and look forward to the ETHOS exacerbation trial results in 2019 that will further characterise the role of this potential treatment for patients with COPD.”
KRONOS trial national co-ordinating investigator Klaus Rabe said: “With the KRONOS trial, we are seeing the potential of PT010 as a triple combination therapy for COPD.
“I expect the triple class of medicines to play an increasingly important role in addressing the needs of the many COPD patients who are currently undertreated or are receiving triple combination therapy as separate medicines in multiple devices.”
The KRONOS trial results will be presented at a forthcoming medical meeting. AstraZeneca anticipates making regulatory submissions in Japan and China in the second half of 2018, followed by potential submissions in the US and Europe in 2019.
PT010 is a single inhaler, fixed-dose triple combination therapy of budesonide, an ICS with glycopyrronium, a LAMA, and formoterol fumarate, a LABA. It is being developed using AstraZeneca’s Aerosphere Delivery Technology. Aerosphere Delivery Technology is also the platform for the approved medicine Bevespi Aerosphere.
ATHENA is AstraZeneca’s Phase III clinical trial programme for PT010, which includes more than 15,500 patients globally across 11 trials.1,6,7,8 The four key trials are ETHOS, KRONOS, TELOS and SOPHOS. ETHOS and TELOS include low and high doses of ICS and stratification of patients by eosinophil levels as part of randomisation, for PT010 and PT009 respectively.6,7
Symbicort is a combination formulation containing budesonide, an ICS, and formoterol, a LABA, in a single inhaler. Symbicort is approved in approximately 120 countries to treat COPD either as Symbicort Turbuhaler or Symbicort pMDI.