FDA Approves TUDORZA® PRESSAIR® (aclidinium bromide inhalation powder) Supplemental New Drug Application (sNDA) to include data for the Reduction of COPD Exacerbations and Hospitalizations

March 29, 2019 Off By BusinessWire

Label Updated to Include Reduction in Exacerbations and Major
Adverse Cardiovascular Event Safety Data in Cardiovascular-Risk COPD
Patients

MORRISVILLE, N.C.–(BUSINESS WIRE)—-Circassia Pharmaceuticals Inc. (“Circassia” or “the Company”), announced
today that the US Food and Drug Administration (FDA) added new data to
the TUDORZA^® PRESSAIR^® (aclidinium bromide
inhalation powder) Prescribing Information that includes data from the
ASCENT trial showing that TUDORZA PRESSAIR reduces exacerbations in
chronic obstructive pulmonary disease (COPD) and does not increase major
adverse cardiovascular events (MACE) in COPD patients with
cardiovascular disease and/or significant cardiovascular risk factors.¹
TUDORZA PRESSAIR is indicated for the maintenance treatment of patients
with COPD.²

According to Kenneth Chapman, MD, Clinical Researcher, Krembil Research
Institute, University Health Network, University of Toronto, and
investigator on the ASCENT trial: “Most people who have COPD are also at
a higher risk for cardiovascular disease because the most common cause
of COPD is long-term smoking. The ASCENT trial was important because it
looked at people who are in this high-risk cardiovascular category. For
a very long time, patients with a high cardiovascular risk were excluded
from long-acting muscarinic antagonist (LAMA) trials, so we were unclear
about the effect of LAMAs on cardiovascular disease; confidence has been
low and questions about its safety have lingered. ASCENT showed that
TUDORZA PRESSAIR use led to clear and consistent reduction in
exacerbations and reductions in flare-ups. This leads to lower emergency
room visits and lower hospital admissions.”

COPD exacerbations, or “flare-ups,” include a sudden worsening of
symptoms such as shortness of breath, worsened cough, headaches.³
Frequent exacerbations accelerate disease progression and death.⁴
Exacerbations also lead to increased unscheduled physician and emergency
room visits, which can add to the financial burden of COPD on
individuals and the healthcare system.⁵

“It was essential to answer the question about major adverse
cardiovascular events and safety in COPD patients with cardiovascular
co-morbidity. The inclusion of the ASCENT safety information in the
updated TUDORZA PRESSAIR label addresses that question,” said Michael
Asmus, Vice President, US Medical Affairs, Circassia. “Exacerbations are
also serious, and sometimes life-threatening events, and it’s gratifying
to make a difference in helping to improve the lives of people who live
with COPD.”

“The expanded label for TUDORZA PRESSAIR is welcome news for the COPD
community and providers who care for COPD patients,” said David Acheson,
Senior Vice President, US Commercial, Circassia. “Circassia is proud to
be a leader in the respiratory health space, and today’s news further
demonstrates our commitment to respiratory health.”

ASCENT was a randomized, double-blind, placebo-controlled of up to
36-months study that evaluated the effect of TUDORZA PRESSAIR on MACE
and exacerbations in 3,630 patients with moderate-to-very-severe COPD.⁶
All patients had a history of cardiovascular or cerebrovascular disease
and/or significant cardiovascular risk factors.⁶This phase
IV trial found that, compared to placebo, TUDORZA PRESSAIR does not
increase MACE and reduced exacerbations in the first year in COPD
patients with high cardiovascular risk.¹ TUDORZA PRESSAIR is
not a rescue medicine and should not be used for treating sudden
breathing problems.² In this study, adverse reactions
occurring at a rate of ≥2% and more common than placebo were nausea,
back pain, cough, hypertension, sinusitis, constipation, arthralgia,
anemia, muscle spasms, cardiac failure congestive, cellulitis, and
gastroesophageal reflux disease.²

Please see complete Important Safety Information below and full
prescribing information here.²

About COPD in the US

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 breathlessness.⁷
According to the American Lung Association, COPD is the third leading
cause of death in the United States.⁸ More than 11 million
people have been diagnosed with COPD, but millions more may have the
disease without knowing it.⁸ COPD causes serious long-term
disability and early death, and the number of people dying from COPD is
growing.⁸

According to the World Health Organization, the most common symptoms of
COPD are breathlessness (or a “need for air”), chronic cough, and sputum
(mucous) production.⁷ 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.⁷
These episodes can be seriously disabling and result in need for urgent
medical care (including hospitalization) and sometimes death.⁷

About TUDORZA PRESSAIR

TUDORZA^® PRESSAIR^® (aclidinium bromide inhalation
powder) is a prescription medicine used two times a day for the
maintenance treatment of COPD.² It is not a rescue medicine
and should not be used for treating sudden breathing problems.²
Full Prescribing Information for TUDORZA PRESSAIR can be found here.²

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 [CircassiaUSA].

Important Safety Information for TUDORZA PRESSAIR

- TUDORZA PRESSAIR is contraindicated in patients with severe
  hypersensitivity to milk proteins or who have hypersensitivity to
  aclidinium bromide or any of the excipients

- TUDORZA PRESSAIR is not indicated for the initial treatment of acute
  episodes of bronchospasm (ie, rescue therapy)

- Immediate hypersensitivity reactions, including anaphylaxis,
  angioedema (swelling of lips, tongue, or throat), urticaria, rash,
  bronchospasm, or itching have occurred after administration of TUDORZA
  PRESSAIR. Additionally, inhaled medicines, including TUDORZA PRESSAIR,
  may cause paradoxical bronchospasm. If any of these occurs, treatment
  with TUDORZA PRESSAIR should be stopped and other treatments considered

- TUDORZA PRESSAIR should be used with caution in patients with
  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 greater than
  placebo) were headache (6.6% vs 5.0%), nasopharyngitis (5.5% vs 3.9%),
  and cough (3.0% vs 2.2%), for TUDORZA PRESSAIR vs placebo,
  respectively. In a long-term 3-year trial, adverse reactions
  (occurring at a rate of ≥2 % and more common than placebo) were
  nausea, back pain, cough, hypertension, sinusitis, constipation,
  arthralgia, anemia, muscle spasms, cardiac failure congestive,
  cellulitis, and gastroesophageal reflux disease

Indication for TUDORZA PRESSAIR

TUDORZA^® PRESSAIR^® (aclidinium bromide inhalation
powder) is an anticholinergic indicated for the maintenance treatment of
patients with chronic obstructive pulmonary disease (COPD).²

You may report side effects related to AstraZeneca products by
clicking here.

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 is marketed under a number of brand names around the
world, including TUDORZA^®, Eklira^®
and Bretaris^®

US-27779 Last Updated 3/19

References:

1. Wise RA, et al. Effects of aclidinium bromide on major adverse
cardiovascular events and COPD exacerbations in patients with COPD and
cardiovascular risk factors. Am J Respir Crit Care Med
2018;197:A7711.

2. TUDORZA^® PRESSAIR^® (aclidinium bromide
inhalation powder) [prescribing information]. Wilmington, DE:
AstraZeneca Pharmaceuticals LP; 2019.

3. COPD Foundation. “Avoiding COPD Exacerbations.” https://www.copdfoundation.org/Learn-More/I-am-a-Person-with-COPD/Avoiding-Exacerbations-and-Pneumonia.aspx
Accessed March 14, 2019.

4. Halpin DMG, et al. Exacerbation frequency and course of COPD. Int
J Chron Obstruct Pulmon Dis. 2012;7:653-661.

5. Dhamane AD, et al. COPD exacerbation frequency and its association
with health care resource utilization and costs. Int J Chron Obstruct
Pulmon Dis. 2015;10:2609-2618.

6. Wise RA, et al. Long-term evaluation of the effects of aclidinium
bromide on major adverse cardiovascular events and COPD exacerbations in
patients with moderate to very severe COPD: rationale and design of the
ASCENT COPD study. Chronic Obstr Pulm Dis. 2018;5(1):5-15.

7. 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.

8. 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.