Circassia Pharmaceuticals launches DUAKLIR® PRESSAIR® (aclidinium/formoterol) for patients with Chronic Obstructive Pulmonary Disease (COPD)

Only twice-daily LAMA /LABA in the United States with COPD exacerbation data included in its prescribing information

MORRISVILLE, N.C.--(BUSINESS WIRE)--Circassia Pharmaceuticals Inc. (“Circassia” or “the Company”), today announced the launch of DUAKLIR® PRESSAIR® (aclidinium bromide and formoterol fumarate) for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).¹ DUAKLIR will be available in the United States on October 21^st and promoted through its dedicated COPD sales force, alongside established COPD treatment TUDORZA® (aclidinium), which is also administered twice-daily via PRESSAIR®. The US launch of DUAKLIR will happen simultaneously with the American College of Chest Physicians’ CHEST Annual Meeting 2019 in New Orleans, LA.

DUAKLIR® PRESSAIR® is a fixed-dose LAMA/LABA combination of the long-acting muscarinic antagonist (LAMA) aclidinium and the long-acting beta agonist (LABA) formoterol. It is administered twice daily via the pre-loaded, breath-actuated, PRESSAIR® multi-dose inhaler.¹ The product is approved worldwide, including in the European Union, under a number of brand names. Approval of DUAKLIR^® is based on data from three Phase III studies, ACLIFORM, AUGMENT and AMPLIFY, and the Phase IV ASCENT-COPD study, which shows aclidinium therapy is effective at reducing exacerbations due to COPD.

David Acheson, SVP, US Commercial, said: “We have diligently built our COPD franchise through strong data and strong products. Today’s launch of DUAKLIR® is the culmination of a strategic and concerted effort to help improve the lives of millions of Americans living with COPD. We are proud of the team at Circassia for working to achieve this important milestone, and are grateful to the researchers and patients for their contributions in helping to bring this important new COPD therapy to the US market.”

As part of Circassia’s launch activities, the Company hosted a Respiratory Educational Reception at the American College of Chest Physicians’ CHEST Annual Meeting 2019. This Reception brought together posters presented at major scientific meetings in the US and Europe detailing results from the AMPLIFY and ASCENT-COPD studies. Circassia presentation at CHEST 2019 includes an Oral Presentation Session #4080 from 1:30-1:45 pm on Monday, October 21, in Room 292 of the Ernest N. Morial Convention Center, 900 Convention Center Blvd, New Orleans, LA 70130.

COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which makes it hard to breathe and results in increased episodes of breathlessness.^2,3 According to the American Lung Association, COPD is the third leading cause of death due to disease in the United States. More than 11 million people have been diagnosed with COPD, but millions more may have the disease without knowing it.⁴ COPD causes serious long-term disability and early death, and the number of people dying from COPD is growing.⁴

The most common symptoms of COPD are breathlessness (or a “need for air”), chronic cough, and sputum (mucus) production.³ Sufferers also frequently experience exacerbations, that is, serious episodes of increased breathlessness, cough and sputum production that last from several days to a few weeks. ³ These episodes can be seriously disabling and result in the need for urgent medical care (including hospitalization) and sometimes death.²

Please see complete Important Safety Information below and full prescribing information here.¹

About the PRESSAIR® Inhaler

DUAKLIR® is administered via the PRESSAIR® Inhaler.¹ The PRESSAIR inhaler has shown to be preferred by patients when compared to other inhaler devices commonly used for COPD.^5,6 PRESSAIR is a multi-dose dry powder inhaler (DPI) that combines two positive feedback mechanisms, and is pre-filled with the DUAKLIR treatment, which relaxes the muscles of the airways, helping to keep them open, allowing the patient to breathe more easily.^1,7

About DUAKLIR® PRESSAIR® Phase-III AMPLIFY Clinical Trial

The FDA approval of DUAKLIR PRESSAIR is based on data from several studies including ACLIFORM,⁸ AUGMENT,⁹ AMPLIFY clinical trial ¹⁰ and ASCENT-COPD study.¹¹

The findings of the AMPLIFY trial (NCT02796677) were published online March 22, 2019, in the International Journal of COPD.¹⁰ This Phase III clinical trial compared the efficacy and safety of inhaled DUAKLIR® PRESSAIR® to its individual components aclidinium and formoterol, and to inhaled Spiriva® Handihaler® (tiotropium) in 1,583 patients with moderate-to-very-severe symptomatic (COPD). The trial found that:

• DUAKLIR PRESSAIR significantly improved lung function versus aclidinium as measured by the change from baseline at 24-weeks in the forced expiratory volume in one second (FEV₁) one-hour post-dose
• DUAKLIR PRESSAIR significantly increased lung function versus formoterol measured by change from baseline in pre-dose morning (trough) FEV₁ at week 24

• A pre-planned sub-study of AMPLIFY in 566 patients measuring lung function over 24-hours demonstrated DUAKLIR PRESSAIR significantly improved lung function at 24-weeks versus Spiriva® (tiotropium) as measured by average area under the curve for FEV₁ obtained from 0 through 24 hours.

“The results of the AMPLIFY trial showed us that the benefits of the combination were more than its individual components in terms of efficacy, with a comparable safety profile,” said Sanjay Sethi, MD, Professor and Chief, Pulmonary, Critical Care and Sleep Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo, and investigator on the AMPLIFY trial. “The study also showed a reduction in the use of rescue inhalers in the DUAKLIR PRESSAIR group, which is a good measure of symptom control in symptomatic COPD patients. DUAKLIR PRESSAIR will be a welcome addition to the armamentarium to help these patients.”

The proportion of patients reporting treatment-related adverse event (AE) was similar between treatment groups in AMPLIFY.¹⁰ The most common adverse events reported in the AMPLIFY¹⁰ study were COPD exacerbations (18.3%), nasopharyngitis (11.8%) and headache (4.9%). The incidence of serious AEs (7.8%), major adverse cardiovascular events (0.7%), and AEs leading to discontinuation (7.1%) or death (0.5%) was very low in AMPLIFY and similar across treatment groups.¹⁰

About Circassia Pharmaceuticals Inc.

Circassia Pharmaceuticals Inc. is part of the Circassia Pharmaceuticals plc group. Circassia is a global specialty pharmaceutical business focused on respiratory disease. The Company sells its market-leading NIOX® asthma management products directly to specialists in the United States, United Kingdom, China, Germany and Italy, and in a wide range of other countries through its network of partners. In the United States, Circassia markets the chronic obstructive pulmonary disease (COPD) treatments TUDORZA® and DUAKLIR®. Circassia also has the US and Chinese commercial rights to the late-stage ventilator-compatible nitric oxide product LungFit PH. For more information please visit www.circassia.com or follow us on Twitter [@CircassiaUSA] and LinkedIn [CircassiaUSA].

Duaklir® and Tudorza® are registered trademarks of Almirall S.A.

Pressair® is a registered trade mark of the AstraZeneca group of companies

Indication and Usage

DUAKLIR® PRESSAIR® (aclidinium bromide/formoterol fumarate inhalation powder) is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

Important Safety Information

• DUAKLIR PRESSAIR (aclidinium bromide/formoterol fumarate inhalation powder) is only indicated for use in COPD and is not indicated for use in asthma. Use of a long-acting beta₂-adrenergic agonist (LABA) as monotherapy, including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, without an inhaled corticosteroid (ICS) is contraindicated in patients with asthma and increases the risk of asthma-related death. When LABA are used in fixed-dose combinations with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone.
• DUAKLIR PRESSAIR is contraindicated in patients with severe hypersensitivity to milk proteins or who have hypersensitivity to aclidinium bromide or formoterol fumarate or any component of the product
• DUAKLIR PRESSAIR is not indicated for the treatment of acute episodes of bronchospasm (i.e. rescue therapy)
• Do not initiate DUAKLIR PRESSAIR with an additional medicine containing a LABA because of risk of overdose or in acutely deteriorating COPD
• Immediate hypersensitivity reactions, including anaphylaxis, angioedema (swelling of lips, tongue, or throat), urticaria, rash, bronchospasm, or itching have occurred after administration of DUAKLIR PRESSAIR. Additionally, inhaled medicines, including DUAKLIR PRESSAIR, may cause paradoxical bronchospasm which may be life threatening. If any of these occurs, immediate treatment with a short acting bronchodilator should be initiated and treatment with DUAKLIR PRESSAIR should be stopped and alternative therapy initiated
• DUAKLIR PRESSAIR should be used with caution in patients with cardiovascular and convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, hypokalemia, hyperglycemia, narrow-angle glaucoma or urinary retention. Instruct patients to consult a physician immediately should any signs or symptoms of acute narrow-angle glaucoma or prostatic hyperplasia or bladder-neck obstruction develop
• The most common adverse reactions (≥3% incidence and more common than placebo) were upper respiratory tract infection (8.9% vs 6.3%), headache (6.3% vs 5.1%), and back pain (3.8% vs 3.4%) for DUAKLIR PRESSAIR vs placebo, respectively. Other adverse reactions reported in clinical studies (>1% but less than 3% and more common than placebo) with DUAKLIR PRESSAIR were cough, sinusitis, influenza, tooth abscess, insomnia, dizziness, dry mouth, oropharyngeal pain, muscle spasm, musculoskeletal pain, arthralgia, pain in extremity, urinary tract infection, and increased blood creatine phosphokinase

Full prescribing information can be found at www.Duaklir.com.

You are encouraged to report negative side effects of prescription drugs to the FDA www.FDA.gov/medwatch or call 1-800-FDA-1088.

Forward-looking statements

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.

Aclidinium bromide/formoterol fumarate is marketed under a number of brand names around the world, including DUAKLIR® Genuair® and Brimica® Genuair®.

References:

^_____________________________ ^1 DUAKLIR® PRESSAIR® (aclidinium bromide/formoterol fumarate inhalation powder) [prescribing information]. Morrisville, NC: Circassia Pharmaceuticals Inc; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210595lbl.pdf. Accessed March 29, 2019.

^2 World Health Organization. Chronic Obstructive Pulmonary Disease (COPD) Fact Sheet. December 1, 2017. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd) Accessed March 15, 2019.

^3 Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2019.

^4 American Lung Association. https://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd/learn-about-copd/how-serious-is-copd.html Accessed March 15, 2019.

^5 Van der Palen J. et al. Preference, satisfaction and errors with two dry powder inhalers in patients with COPD. Expert Opin Drug Deliv 2013;10 (8):1023-1031.

^6 Pascual S. et al. Preference, satisfaction and critical errors with GENUAIR and Breezhaler inhalers in patients with COPD: a randomised, cross-over, multicentre study. Primary Care Respiratory Medicine 2015; 25, 15018; doi:10.1038/npjpcrm.2015.18; Published online April 30 2015.

^7 Gavaldà A. et al. Characterization of aclidinium bromide, a novel inhaled muscarinic antagonist, with long duration of action and a favorable pharmacological profile. J Pharmacol Exp Ther 2009;331:740-51.

^8 Singh D. et al. Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study. BMC Pulmonary Medicine. 2014;14:178.

^9 D’Urzo A. et al. Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study. Respiratory Research. 2014;15:123.

^10 Sethi S. et al. AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD. Int. J. COPD 2019:14 667—682. International Journal of COPD 14 2019 667 to 682. Accessed March 22, 2019.

^11 Wise RA, Chapman KR, Scirica BM, et al. Effect of Aclidinium Bromide on Major Cardiovascular Events and Exacerbations in High-Risk Patients With Chronic Obstructive Pulmonary Disease: The ASCENT-COPD Randomized Clinical Trial. JAMA. 2019;321(17):1693-1701. doi:10.1001/ jama.2019.4973.