Successful KRONOS Phase III trial of triple therapy (PT 010) for COPD. AstraZeneca

AstraZeneca has announced publication of results from the KRONOS Phase III trial which evaluated the efficacy and safety of triple combination therapy PT 010 (budesonide/ glycopyrronium/formoterol fumarate) versus dual combination therapies Bevespi Aerosphere (glycopyrronium/formoterol fumarate), Symbicort Turbuhaler (budesonide/formoterol fumarate) and PT009 (budesonide/formoterol fumarate) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) regardless of whether or not they had an exacerbation in the prior year.

The KRONOS trial met eight of the nine primary lung function endpoints and, in a key secondary endpoint, PT 010 showed a statistically significant 52% reduction in the rate of moderate or severe COPD exacerbations compared with Bevespi Aerosphere in a patient population that was not required to have had an exacerbation in the previous 12 months. PT 010 also demonstrated reductions in the rate of moderate or severe COPD exacerbations versus PT 009 and Symbicort (18% and 17% respectively), which were numerically but not statistically significant improvements. The incidence of adjudicated pneumonia was low and comparable in all treatment arms. The data were presented at the European Respiratory Society (ERS) International Congress 2018 in Paris, France, and published in The Lancet Respiratory Medicine.

Gary Ferguson, Professor of the Pulmonary Research Institute of Southeast Michigan, Livonia, Michigan and lead author of the KRONOS trial publication, said: �Preventing exacerbations is a priority in the management of COPD because they are known to have an impact on lung function and mortality, and patients are at risk even if they haven�t had an exacerbation in the previous 12 months. The KRONOS trial demonstrated that PT 010 reduces the risk of an exacerbation versus LAMA/LABA combination therapy in symptomatic COPD patients regardless of whether or not they�ve had an exacerbation in the previous year.�

There were no new or unexpected safety or tolerability signals for PT 010 in the KRONOS trial, and the adverse events profile was consistent with that observed in previous trials. The most frequently reported adverse events were nasopharyngitis, upper respiratory tract infection, COPD, bronchitis, muscle spasms, dysphonia, hypertension, dyspnoea, back pain and nausea. The incidence of adjudicated pneumonia was low and comparable among PT010 (1.9%), Bevespi Aerosphere (1.6%), PT009 (1.9%) and Symbicort Turbuhaler (1.3%).

Comment:AstraZeneca anticipates making the first regulatory submissions for PT010 in the second half of 2018.

See-Ferguson GT, Rabe KF, Martinez FJ, et al." Triple combination of budesonide/glycopyrrolate /formoterol fumarate using co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, randomised controlled trial"-. Lancet Respir Med 2018; Sep 16. [Epub ahead of print] https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(18)30327-8/fulltext.