AstraZeneca has announced positive top-line results of the phase IV ASCENT trial for Tudorza Pressair (aclidinium bromide 400 µg, twice-daily), a long-acting muscarinic antagonist (LAMA), in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), with a history of cardiovascular disease and/or significant cardiovascular risk factors.
When added to background therapy, Tudorza met the primary efficacy endpoint, demonstrating a statistically significant reduction in the annual rate of moderate or severe COPD exacerbations compared to placebo. Tudorza also met the primary safety endpoint, demonstrating time to first major adverse cardiovascular event (MACE) comparable to placebo. In the trial patients were randomised to receive Tudorza or placebo.
Tudorza, also marketed as Eklira and Bretaris, is available in more than 50 countries. Aclidinium bromide is also the LAMA in Duaklir (aclidinium bromide/formoterol fumarate), which is marketed in more than 30 countries and under development for the US and China.
Steve Lewington, Global Medicine Leader, Respiratory, AstraZeneca, said: “The ASCENT data demonstrate that Tudorza, when added to background therapy, reduces exacerbation rates in patients with cardiovascular disease or risk factors and adds to the established efficacy and safety profile of aclidinium bromide. Based on these results, AstraZeneca plans to submit an sNDA for an expanded label for Tudorza in the US.”
Dr. Kenneth Chapman, Professor of Medicine in the Faculty of Medicine University of Toronto, said: “Cardiovascular disease is the most common comorbidity for patients living with COPD. It is therefore very encouraging to see that aclidinium is effective in reducing exacerbation rates with no increase in cardiovascular events in this at-risk patient population.”
ASCENT is a post-marketing requirement (PMR) trial requested by the US Food and Drug Administration (FDA) to evaluate MACE for up to three years with aclidinium bromide. The trial included more than 3,600 patients from Canada and the US. The safety and tolerability profile of Tudorza was consistent with its label.
A full analysis of the data is ongoing. Full results will be provided to the US FDA and presented at a forthcoming medical meeting. AstraZeneca plans to submit an sNDA for an expanded Tudorza label.
In April 2017, AstraZeneca entered a strategic collaboration with Circassia Pharmaceuticals for the development and commercialisation of Tudorza and Duaklir (aclidinium bromide/formoterol) in the US.