AstraZeneca announced top-line results from the Phase III KRONOS trial that 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 chronic obstructive pulmonary disease (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). Patients were given two inhalations twice a day of PT010, PT009, Bevespi Aerosphere or Symbicort Turbuhaler.
There were no unexpected safety or tolerability signals for PT010 identified in the trial.
Summary of trial results:
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Primary endpoint results assessed by FEV1 |
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PT010 vs Symbicort |
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Over 24 weeks (post-dose*) |
Met |
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PT010 vs Bevespi Aerosphere |
|
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Over 24 weeks (trough) |
Met |
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Over 12-24 weeks (trough) |
Met |
|
At 24 weeks (trough) |
Not met; favourable trend |
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PT010 vs PT009 |
|
|
Over 24 weeks (post-dose*) |
Met |
|
Over 12-24 weeks (trough) |
Met |
|
At 24 weeks (post-dose*) |
Met |
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PT009 vs Symbicort (non-inferiority comparison) |
|
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Over 24 weeks (trough) |
Met |
|
Over 12-24 weeks (trough) |
Met |
* Post-dose assessments FEV1 area under the curve 0-4 hours
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.”
Klaus Rabe, Professor of Pulmonary Medicine at the University of Kiel, Director of the Department of Pneumology at Clinic Grosshansdorf, Germany, and National Co-ordinating Investigator of the KRONOS trial, 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.
Filed Under: Drug Discovery
