-- Study to investigate antiviral activity and improvement in
oxygenation and pulmonary arterial pressure in patients suffering
from COVID-19 --
STAINES-UPON-THAMES, United
Kingdom and GARDEN GROVE,
Calif., April 1, 2020
/PRNewswire/ -- Mallinckrodt
plc (NYSE: MNK), a global biopharmaceutical company, and
Novoteris, LLC, a clinical stage medical device and pharmaceutical
developer focused on innovative nitric oxide gas
applications, today announced that the Therapeutic Products
Directorate of Health Canada has cleared the companies' joint pilot
clinical trial, entitled "Inhaled Gaseous Nitric Oxide (gNO)
Antimicrobial Treatment of Difficult Bacterial and Viral Lung
(COVID-19) Infections" application to investigate the use of
Thiolanox®, a high-dose inhaled nitric oxide therapy for
the treatment of patients infected with novel coronavirus
(SARS-CoV-2) at Vancouver Coastal Health Authority facilities. The
investigative therapy employs Novoteris' Inhaled Nitric Oxide
Delivery Device (INODD) and Mallinckrodt's high-concentration, 5000 PPM nitric
oxide gas for inhalation canisters. The study will investigate the
therapy's safety and effectiveness in treating COVID-19 and its
associated lung complications. The companies expect to begin
recruiting patients in the coming days.
"Inhaled nitric oxide may have an antiviral effect, as well as
improve oxygenation and pulmonary arterial pressure in patients
suffering from COVID-19," said Steven
Romano, M.D., Executive Vice President and Chief Scientific
Officer at Mallinckrodt. "We're
proud to be partnering with Novoteris on this pilot trial and are
committed to increasing understanding of this potentially important
therapeutic option for healthcare providers on the front lines of
this unprecedented health emergency."
COVID-19 is a contagious respiratory illness caused by a novel
coronavirus. Patients with COVID-19 have mild to severe respiratory
illness that can include symptoms such as cough, fever and
shortness of breath.1 In severe cases, COVID-19 can
cause acute respiratory distress syndrome (ARDS) – a disorder in
which fluid leaks into the lungs, making breathing difficult or
impossible – and can lead to multi-organ failure and sometimes
death.1,2
"Our collaboration with Mallinckrodt
to study high-dose inhaled nitric oxide to treat patients with
COVID-19 and associated lung complications is an exciting step in
both companies' commitment to helping the world battle this global
pandemic," said Alex Stenzler,
Founder and President at Novoteris.
Inhaled nitric oxide (iNO) has been evaluated in randomized
controlled trials, both in pediatric and adult patients with
ARDS,3,4,5,6,7 and demonstrated partially dose-dependent
improvement in blood oxygenation and decreased pulmonary artery
pressure3 and, in one trial, improvements in the
composite measure of days alive or free of ventilator support at
day 28 of the trial (the last day evaluated).8 There
have been other trials evaluating iNO in the context of ARDS, which
have demonstrated mixed results.6,7,9 In an in
vitro study, inhaled nitric oxide has demonstrated an
inhibitory effect on the replication cycle of severe acute
respiratory syndrome-related coronavirus (SARS-CoV).10
Furthermore, a small clinical trial in SARS-CoV patients
demonstrated improvements in blood oxygenation, a reduction in
supplemental oxygen and a reduction in the amount of ventilator
support.11
"This is an important day for patients and healthcare
providers," said Chris Miller,
Ph.D., Assistant Professor, Faculty of Medicine at University of British Columbia and Founder and
Scientific Advisor at Novoteris. Dr. Miller, team
lead for the study at Vancouver Coastal Health Research Institute,
and an expert in nitric oxide therapies, with a research career
spanning more than 25 years studying the antimicrobial effect of
high-dose nitric oxide to treat lung infections, said, "I am very
pleased to be working with Mallinckrodt
and Novoteris on this study using high-dose inhaled nitric oxide
for patients with COVID-19."
Mallinckrodt is currently working
with the U.S. Food and Drug Administration on the possibility of
making the company's INOmax® (nitric oxide) gas, for
inhalation product available to U.S. patients with pulmonary
complications of COVID-19 as quickly as possible through the
appropriate regulatory mechanism. INOmax has been on the
market in the U.S. since 2000, and is indicated for the treatment
of term and near-term neonates with hypoxic respiratory failure
associated with pulmonary hypertension. Please see Important Safety
Information below. The safety and efficacy of INOmax and iNO for
pulmonary complications associated with COVID-19 have not been
established.
For more information, please visit clinicaltrials.gov.
Canada – Indications and
Important Safety Information
INDICATIONS & CLINICAL USE
- INOmax, in conjunction with ventilatory support and other
appropriate agents, is indicated for the treatment of term and late
pre-term (≥ 34 weeks) neonates with hypoxic respiratory failure
associated with clinical or echocardiographic evidence of pulmonary
hypertension, where it improves oxygenation and reduces the need
for extracorporeal membrane oxygenation.
- The safety and effectiveness of INOmax have been established in
a population receiving other therapies for hypoxic respiratory
failure, including vasodilators, intravenous fluids, bicarbonate
therapy, and mechanical ventilation.
- In clinical trials, no efficacy has been demonstrated with the
use of INOmax in patients with congenital diaphragmatic
hernia.
CONTRAINDICATIONS
- In patients where systemic oxygenation is wholly dependent on
extra-pulmonary right-to-left shunting, use of INOmax has the
potential to decrease right-to-left blood flow, which, in this
condition, is potentially fatal.
MOST SERIOUS WARNINGS & PRECAUTIONS
- Left-to-Right Shunting: Treatment might aggravate
cardiac insufficiency due to unwanted pulmonary vasodilation caused
by inhaled nitric oxide, resulting in a further increase of already
existing pulmonary hyperperfusion. It is recommended to perform
pulmonary artery catheterization or echocardiographic examination
of central hemodynamics prior to administration.
OTHER RELEVANT WARNINGS & PRECAUTIONS
- If clinical response is inadequate at 4-6 hours after starting
INOmax: availability of nitric oxide on transport to another
hospital should be assured to prevent worsening of condition on
acute discontinuation of INOmax. Rescue, such as ECMO, should be
considered on continued deterioration or failure to improve,
defined by local hospital criteria.
- INOmax should not be discontinued abruptly as it may result in
rebound pulmonary hypertension. If rebound pulmonary hypertension
occurs, reinstate therapy immediately.
- Neonates are known to have diminished methemoglobin reductase
activity and could be at greater risk of developing
methemoglobinemia.
- NO2 rapidly forms in gas mixtures containing nitric oxide and
O2, and nitric oxide may in this way cause airway inflammation and
damage.
- Patients with left ventricular dysfunction treated with inhaled
nitric oxide, experienced serious adverse events. Discontinue
INOmax while providing symptomatic care.
- Animal models have shown that nitric oxide may interact with
homeostasis, resulting in an increased bleeding time. Data in adult
humans are conflicting.
For more information please consult the product monograph at
https://www.mallinckrodt.ca/wp-content/uploads/2017/11/INOMAX-Product-Monograph.pdf for
important information relating to adverse reactions, drug
interactions, and dosing information which have not been discussed
in this piece. The product monograph is also available by calling
us at 1-855-399-6742.
U.S. – Indications and Important Safety Information
INDICATION
INOmax® (nitric oxide) gas, for inhalation, is
indicated to improve oxygenation and reduce the need for
extracorporeal membrane oxygenation in term and near-term (>34
weeks gestation) neonates with hypoxic respiratory failure
associated with clinical or echocardiographic evidence of pulmonary
hypertension in conjunction with ventilatory support and other
appropriate agents.
IMPORTANT SAFETY INFORMATION
- INOmax is contraindicated in the treatment of neonates
dependent on right-to-left shunting of blood.
- Abrupt discontinuation of INOmax may lead to increasing
pulmonary artery pressure and worsening oxygenation.
- Methemoglobinemia and NO2 levels are dose dependent.
Nitric oxide donor compounds may have an additive effect with
INOmax on the risk of developing methemoglobinemia. Nitrogen
dioxide may cause airway inflammation and damage to lung
tissues.
- In patients with pre-existing left ventricular dysfunction,
INOmax may increase pulmonary capillary wedge pressure leading to
pulmonary edema.
- Monitor for PaO2, inspired NO2, and
methemoglobin during INOmax administration.
- INOmax must be administered using a calibrated FDA-cleared
Nitric Oxide Delivery System.
Please see Full Prescribing
Information.
ABOUT MALLINCKRODT
Mallinckrodt is a global business consisting of
multiple wholly owned subsidiaries that develop, manufacture,
market and distribute specialty pharmaceutical products and
therapies. The company's Specialty Brands reportable segment's
areas of focus include autoimmune and rare diseases in specialty
areas like neurology, rheumatology, nephrology, pulmonology and
ophthalmology; immunotherapy and neonatal respiratory critical care
therapies; analgesics and gastrointestinal products. Its Specialty
Generics reportable segment includes specialty generic drugs and
active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.
Mallinckrodt uses its website as a
channel of distribution of important company information, such as
press releases, investor presentations and other financial
information. It also uses its website to expedite public access to
time-critical information regarding the company in advance of or in
lieu of distributing a press release or a filing with the U.S.
Securities and Exchange Commission (SEC) disclosing the same
information. Therefore, investors should look to the Investor
Relations page of the website for important and time-critical
information. Visitors to the website can also register to receive
automatic e-mail and other notifications alerting them when new
information is made available on the Investor Relations page of the
website.
ABOUT NOVOTERIS, LLC
Novoteris, LLC is a privately
held limited liability company managed by a group of international
industry veterans and clinicians involved in developing and
producing innovative, cutting-edge medical products. The company
was formed in 2013 to consolidate the nitric oxide assets and other
resources from 12th Man Technologies, Inc. (Garden Grove, CA) and Nitric Solutions, Inc.
(Vancouver, Canada) for the
completion of inhaled nitric oxide trials for the treatment of
patients with cystic fibrosis. The company received Orphan Drug
designations for the treatment of cystic fibrosis from both the FDA
and EMA in 2013. Novoteris is headquartered in Garden Grove, California with an EU entity in
Belgium (Novoteris GVC). For
additional information, please visit www.novoteris.com.
CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING
STATEMENTS
This release includes forward-looking statements
concerning inhaled nitric oxide ("iNO") and Mallinckrodt's INOmax product, including statements
with regard to potential regulatory developments, the potential
impact of iNO on patients and anticipated benefits associated with
its use, as well as statements related to COVID-19. The statements
are based on assumptions about many important factors, including
the following, which could cause actual results to differ
materially from those in the forward-looking statements: clinical
trial results; the impact of the outbreak of the COVID-19
coronavirus; satisfaction of regulatory and other requirements;
actions of regulatory bodies and other governmental authorities;
changes in laws and regulations; issues with product quality,
manufacturing or supply, or patient safety issues; and other risks
identified and described in more detail in the "Risk Factors"
section of Mallinckrodt's most recent
Annual Report on Form 10-K and other filings with the SEC, all of
which are available on its website. The forward-looking statements
made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to
update or revise any forward-looking statement, whether as a result
of new information, future events and developments or otherwise,
except as required by law.
CONTACTS
For Trade Media
Inquiries
Caren Begun
Green Room Communications
201-396-8551
caren@greenroompr.com
Alex Stenzler
President, Novoteris, LLC
714-705-4576
alex.stenzler@12thmantec.com
Stephania Manusha
Director, Clinical Trials Administration
Vancouver Coastal Health & Research Center
604.675.2567
stephania.manusha@vch.ca
Investor Relations
Daniel J.
Speciale, CPA
Vice President, Investor Relations and IRO
314-654-3638
daniel.speciale@mnk.com
Government Affairs
Mark
Tyndall
Senior Vice President, Government Affairs
202-383-0090
mark.tyndall@mnk.com
Mallinckrodt, the "M" brand mark and
the Mallinckrodt Pharmaceuticals logo are trademarks of
a Mallinckrodt company. Other brands are trademarks of
a Mallinckrodt company or their respective
owners. ©2020 Mallinckrodt. US-2000677 04/20
References
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