Phase IV ASCENT trial meets primary endpoints in COPD patients
with cardiovascular risk factors
Findings support supplemental New Drug Application (sNDA)
LONDON, UK I December 4, 2017 I AstraZeneca today 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.
NOTES TO EDITORS
About COPD
COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 329 million people worldwide and is predicted to be the third leading cause of death by 2020. Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important to the management of COPD. Cardiovascular comorbidities are one of the most frequent systemic manifestations that have the biggest effect on patients with COPD, contributing substantially to disease progression, clinical outcomes, mortality and resource use.
About ASCENT
ASCENT is a double-blind, randomised, placebo-controlled, parallel-group, Phase IV trial to evaluate the effect of Tudorza on time to first MACE and reduction of moderate or severe exacerbations in patients with moderate to very severe COPD. Both Tudorza and placebo were administered twice-daily (morning and evening) via the Pressair dry-powder inhaler (DPI). Patients in the trial also continued background therapy including maintenance and reliever medications and excluding anticholinergics. The rate of moderate or severe COPD exacerbations was measured per patient per year during the first year of treatment. MACE is a composite measure of the total of cardiovascular death, non-fatal heart attack and non-fatal stroke. ASCENT was conducted in 3,630 patients and concluded after at least 122 patients had experienced an adjudicated MACE.
About Tudorza
Tudorza (aclidinium bromide) is a LAMA delivered through the Pressair DPI. Tudorza was approved in the US in 2012 for the long-term maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema. Aclidinium bromide was approved in Europe in 2012 for the maintenance treatment of COPD. Globally, it is now available to patients in more than 50 countries under the Tudorza, Eklira and Bretaris brand names. Aclidinium bromide is the LAMA in Duaklir (aclidinium bromide/formoterol fumarate), which is approved in more than 30 countries and under development for the US and China.
About Circassia
In April 2017, AstraZeneca entered a strategic collaboration with Circassia Pharmaceuticals for the development and commercialisation of Tudorza and Duaklir in the US. Under the terms of the collaboration Circassia was granted the rights to Duaklir in the US. Circassia is also leading the promotion of Tudorza in the US and was granted an option to gain the full commercial rights in the future. AstraZeneca has received a minority equity stake in Circassia. AstraZeneca will complete ongoing development activities and continue to manufacture and supply both medicines. AstraZeneca will receive $100 million at the approval of Duaklir in the US, or 30 June 2019, whichever is earliest, and Circassia will pay AstraZeneca tiered percentage royalties on potential future US sales of Duaklir.
About AstraZeneca in Respiratory Disease
Respiratory disease is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients in 2016. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification.
The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans both pMDIs and dry powder inhalers, as well as the innovative Aerosphere Delivery Technology. The company’s biologics include Fasenra (anti-eosinophil, anti-IL-5Rɑ), which is now approved in the US, received a positive CHMP opinion in the EU and is under regulatory review in Japan, tralokinumab (anti-IL-13), which has completed Phase III trials, and tezepelumab (anti-TSLP), which successfully achieved its Phase IIb primary and secondary endpoints. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
SOURCE: AstraZeneca
Post Views: 17
Phase IV ASCENT trial meets primary endpoints in COPD patients
with cardiovascular risk factors
Findings support supplemental New Drug Application (sNDA)
LONDON, UK I December 4, 2017 I AstraZeneca today 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.
NOTES TO EDITORS
About COPD
COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 329 million people worldwide and is predicted to be the third leading cause of death by 2020. Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important to the management of COPD. Cardiovascular comorbidities are one of the most frequent systemic manifestations that have the biggest effect on patients with COPD, contributing substantially to disease progression, clinical outcomes, mortality and resource use.
About ASCENT
ASCENT is a double-blind, randomised, placebo-controlled, parallel-group, Phase IV trial to evaluate the effect of Tudorza on time to first MACE and reduction of moderate or severe exacerbations in patients with moderate to very severe COPD. Both Tudorza and placebo were administered twice-daily (morning and evening) via the Pressair dry-powder inhaler (DPI). Patients in the trial also continued background therapy including maintenance and reliever medications and excluding anticholinergics. The rate of moderate or severe COPD exacerbations was measured per patient per year during the first year of treatment. MACE is a composite measure of the total of cardiovascular death, non-fatal heart attack and non-fatal stroke. ASCENT was conducted in 3,630 patients and concluded after at least 122 patients had experienced an adjudicated MACE.
About Tudorza
Tudorza (aclidinium bromide) is a LAMA delivered through the Pressair DPI. Tudorza was approved in the US in 2012 for the long-term maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema. Aclidinium bromide was approved in Europe in 2012 for the maintenance treatment of COPD. Globally, it is now available to patients in more than 50 countries under the Tudorza, Eklira and Bretaris brand names. Aclidinium bromide is the LAMA in Duaklir (aclidinium bromide/formoterol fumarate), which is approved in more than 30 countries and under development for the US and China.
About Circassia
In April 2017, AstraZeneca entered a strategic collaboration with Circassia Pharmaceuticals for the development and commercialisation of Tudorza and Duaklir in the US. Under the terms of the collaboration Circassia was granted the rights to Duaklir in the US. Circassia is also leading the promotion of Tudorza in the US and was granted an option to gain the full commercial rights in the future. AstraZeneca has received a minority equity stake in Circassia. AstraZeneca will complete ongoing development activities and continue to manufacture and supply both medicines. AstraZeneca will receive $100 million at the approval of Duaklir in the US, or 30 June 2019, whichever is earliest, and Circassia will pay AstraZeneca tiered percentage royalties on potential future US sales of Duaklir.
About AstraZeneca in Respiratory Disease
Respiratory disease is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients in 2016. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification.
The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans both pMDIs and dry powder inhalers, as well as the innovative Aerosphere Delivery Technology. The company’s biologics include Fasenra (anti-eosinophil, anti-IL-5Rɑ), which is now approved in the US, received a positive CHMP opinion in the EU and is under regulatory review in Japan, tralokinumab (anti-IL-13), which has completed Phase III trials, and tezepelumab (anti-TSLP), which successfully achieved its Phase IIb primary and secondary endpoints. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
SOURCE: AstraZeneca
Post Views: 17
