Circassia Announces Duaklir® Successfully Met Primary Endpoints in AMPLIFY Phase III Study in Chronic Obstructive Pulmonary Disease
– NDA submission planned H1 2018 by partner AstraZeneca –
– Filing supported by positive results from ACHIEVE dose-ranging study –
– Circassia has exclusive commercialisation rights to Duaklir® in the United States –
Oxford, UK – 7 September 2017: Circassia Pharmaceuticals plc (“Circassia” or “the Company”; LSE: CIR), a specialty pharmaceutical company focused on respiratory disease, today announces positive top-line results from the AMPLIFY phase III study of Duaklir®* in chronic obstructive pulmonary disease (COPD), which was conducted by the Company’s partner AstraZeneca. Duaklir® is a fixed-dose combination of the long-acting muscarinic antagonist (LAMA) aclidinium bromide and long-acting beta-agonist (LABA) formoterol fumarate, administered via the Pressair®** inhaler.
The AMPLIFY study met its co-primary efficacy endpoints with Duaklir® demonstrating statistically significant and clinically meaningfully improvements in lung function, measured by forced expiratory volume in one second (FEV1), compared with the combination’s individual component monotherapies (aclidinium and formoterol). Aclidinium monotherapy (Tudorza®*** Pressair®) also achieved its primary bronchodilation endpoint demonstrating non-inferiority to tiotropium (Spiriva® Handihaler®). Additionally, a sub-study of 24-hour bronchodilation demonstrated statistically significant greater night-time bronchodilation for twice-daily Duaklir® and Tudorza® compared to once-daily Spiriva®. The safety profiles of Duaklir® and its individual components were consistent with previous studies. A full evaluation of the AMPLIFY data is ongoing and the results will be submitted for presentation at a forthcoming medical meeting.
Under the April 2017 collaboration established between Circassia and AstraZeneca, Circassia has exclusive commercialisation rights to Duaklir® in the United States and AstraZeneca is responsible for conducting the product’s development. Circassia also has responsibility for marketing Tudorza® in the United States.
Following the completion of the AMPLIFY study, AstraZeneca plans to file a New Drug Application (NDA) for Duaklir® with the United States Food and Drug Administration (FDA) during the first half of 2018. In addition to AMPLIFY’s positive clinical results, AstraZeneca and Circassia believe the study trial materials’ in vitro comparability data also meet FDA requirements.
The Duaklir® NDA will include results from the recently-completed ACHIEVE dose-ranging study. This compared the bronchodilation effects of three doses of formoterol delivered twice daily via Pressair® (6 µg, 12 µg and 24 µg) with nebulised formoterol (Perforomist® inhalation solution 20 µg twice daily). The study’s results support the 12 µg dose of formoterol included in the AMPLIFY study as the optimal dose for inhalation via Pressair®. As part of the regulatory process, AstraZeneca intends to seek a pre-NDA meeting with the FDA in the coming months.
Steve Harris, Circassia’s Chief Executive, said: “We are delighted with these positive phase III results and believe Duaklir® has the potential to provide a valuable treatment option for COPD patients in the United States. With treatment guidelines now placing a greater emphasis on LAMA / LABA combinations, we look forward to our partner AstraZeneca filing an NDA for Duaklir® in the coming months.”
Steve Lewington, Global Medicine Leader, Respiratory, AstraZeneca said: “The AMPLIFY study top-line results provide further clinical evidence of Duaklir®’s efficacy and support making this LAMA / LABA combination treatment option available to COPD patients in the US.”
AMPLIFY was a randomised, parallel-group, double-blind, multinational phase III study. It enrolled over 1,500 patients with stable COPD in the United States, United Kingdom, Germany, Spain, Poland, Czechia, Hungary, Bulgaria, Ukraine and Israel. The 24-week study compared the efficacy and safety of Duaklir® (aclidinium bromide 400µg / formoterol fumarate 12µg fixed-dose combination administered twice daily via Pressair® inhaler) with each of the combination’s individual components as monotherapies (aclidinium bromide 400µg and formoterol fumarate 12µg both administered twice daily via Pressair® inhaler). The study had two co-primary efficacy outcome measures:
- Change from baseline in FEV1 one hour post dosing in the Duaklir® group compared with patients receiving aclidinium monotherapy.
- Change in FEV1 from baseline prior to morning dosing (trough) in the Duaklir® group compared with the formoterol monotherapy group.
The study also had a primary endpoint relating to Tudorza® (aclidinium monotherapy). This compared the change from baseline in morning pre-dose FEV1 (trough) in the aclidinium monotherapy group with patients receiving Spiriva® (tiotropium 18µg once-daily administered via Handihaler®).
AMPLIFY’s secondary outcomes included additional comparisons of lung function and health-related quality of life measures between the combination therapy and individual component monotherapy groups. Additional efficacy variables included symptom and COPD exacerbation measures.
Analyst conference call
Circassia will host an analyst conference call today at 09:00 BST. For further details please contact Mo Noonan on +44 (0) 20 3727 1390.
Circassia is a world-class specialty pharmaceutical business focused on respiratory disease. Circassia sells its novel, market-leading NIOX® asthma management products directly to specialists in the United States, United Kingdom and Germany, and in a wide range of other countries through its network of partners. The Company recently established a collaboration with AstraZeneca in the US in which it promotes the chronic obstructive pulmonary disease (COPD) treatment Tudorza®, and has the US commercial rights to late-stage COPD product Duaklir®.
Circassia’s development pipeline includes a range of respiratory medicines. The Company’s lead asthma treatment targets substitution of GSK’s Flixotide® pMDI and was approved in the UK. Circassia is also developing a direct substitute for Seretide® pMDI, and its pipeline includes a number of inhaled medicines for COPD, including single and combination dose products. For more information on Circassia please visit www.circassia.com.
Steve Harris, Chief Executive Officer Tel: +44 (0) 1865 405 560
Julien Cotta, Chief Financial Officer
Rob Budge, Corporate Communications
JP Morgan Cazenove
James Mitford / James Deal Tel: +44 (0) 20 7742 4000
Clare Terlouw / Freddie Barnfield Tel: +44 (0) 20 7260 1000
Ben Atwell / Simon Conway / Mo Noonan Tel: +44 (0) 20 3727 1000
*Duaklir® is a registered trademark in Europe and other markets; the US trademark is subject to review and approval by the FDA
**Outside of the US the Pressair® inhaler is marketed as Genuair®
***Aclidinium monotherapy is marketed under a number of brand names, including Tudorza®, Eklira® and Bretaris®
Duaklir®, Pressair®, Genuair® and Tudorza® are all registered trademarks of AstraZeneca
This press release contains certain projections and other forward-looking statements with respect to the financial condition, results of operations, businesses and prospects of Circassia. The use of terms such as “may”, “will”, “should”, “expect”, “anticipate”, “project”, “estimate”, “intend”, “continue”, “target” or “believe” and similar expressions (or the negatives thereof) are generally intended to identify forward-looking statements. These statements are based on current expectations and involve risk and uncertainty because they relate to events and depend upon circumstances that may or may not occur in the future. There are a number of factors that could cause actual results or developments to differ materially from those expressed or implied by these forward-looking statements. Any of the assumptions underlying these forward-looking statements could prove inaccurate or incorrect and therefore any results contemplated in the forward-looking statements may not actually be achieved. Nothing contained in this press release should be construed as a profit forecast or profit estimate. Investors or other recipients are cautioned not to place undue reliance on any forward-looking statements contained herein. Circassia undertakes no obligation to update or revise (publicly or otherwise) any forward-looking statement, whether as a result of new information, future events or other circumstances.