US Food and Drug Administration Approves 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 that the US Food and Drug Administration has approved DUAKLIR®
PRESSAIR® (aclidinium bromide and formoterol fumarate) for the
maintenance treatment of patients with chronic obstructive pulmonary
disease (COPD).¹

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.

In April 2017, Circassia and AstraZeneca established a commercial
collaboration in the United States under which Circassia has exclusive
US commercialization rights to DUAKLIR PRESSAIR and AstraZeneca
is responsible for the product’s development and regulatory submission.

“Our collaboration with AstraZeneca throughout the DUAKLIR PRESSAIR
regulatory process has been overwhelmingly positive,” said David
Acheson, Senior Vice President, US Commercial, Circassia. “We look
forward to bringing DUAKLIR PRESSAIR to market in the coming
months as an important expansion of Circassia’s COPD and respiratory
health portfolio.”

“The FDA approval of DUAKLIR PRESSAIR gives COPD patients a new,
effective and safe option in LAMA/LABA therapy, enabling them to receive
maximal improvement in lung function delivered through a unique
dry-powder inhaler,” said Michael Asmus, Vice President, US Medical
Affairs, Circassia.

COPD (chronic obstructive pulmonary disease) 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 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 and
the recently-published AMPLIFY clinical trial.¹⁰

The findings of the AMPLIFY trial (NCT02796677)
were published online March 22, 2019 in the International Journal of
COPD originally published by Dove Medical Press Ltd International
Journal of COPD 14 2019 667 to 682.¹⁰ 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
• Overall nighttime and early-morning symptom severity scores (as
  measured by NiSCI and EMSCI questionnaires) showed numerical
  improvements with DUAKLIR PRESSAIR compared to aclidinium or
  formoterol over 24 weeks and significant improvements in overall
  early-morning symptom severity score versus Spiriva® Handihaler®
  (tiotropium)
• 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 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, China and Germany, and in a wide
range of other countries through its network of partners. In the United
States, Circassia has a commercial collaboration with AstraZeneca in
which it has the commercial rights to chronic obstructive pulmonary
disease (COPD) treatments TUDORZA PRESSAIR and DUAKLIR® PRESSAIR®.
Circassia also has the commercial rights to the late-state
ventilator-compatible nitric oxide product AirNOvent in the United
States and China. For more information please visit www.circassia.com,
or follow us on Twitter
@CircassiaUSA and LinkedIn.

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]. Wilmington, DE:
AstraZeneca Pharmaceuticals LP; 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. April
2019 PP-DUA-US-0002 v3.0

Contacts

Rebecca Novak Tibbitt
[email protected]
Ph:
(704) 341-1544