STAINES-UPON-THAMES, United
Kingdom, May 4, 2020
/PRNewswire/ -- Mallinckrodt
plc (NYSE: MNK), a global biopharmaceutical company, today
announced that its observational registry comparing the safety and
effectiveness of INOmax® (nitric oxide) gas, for
inhalation, in term and near-term neonates to that in preterm
neonates with pulmonary hypertension (PH) was ended early due to
achievement of the pre-specified primary outcome measure,
non-inferiority (95 percent confidence interval: -0.0021, 0.1158,
with a pre-defined margin of -0.1452). The decision was made
following the second planned interim analysis at 75 percent
enrollment. The company intends to share the results of this study
in an appropriate scientific forum soon.
INOmax is indicated for the treatment of term and near-term
neonates with hypoxic respiratory failure associated with pulmonary
hypertension. The safety and efficacy of INOmax in premature
neonates has not been evaluated by the U.S. Food and Drug
Administration.
Persistent pulmonary hypertension of the newborn (PPHN) is a
serious and sometimes fatal cardiorespiratory complication of the
transition to extra-uterine life.1,2 The registry
trial was conducted to examine the utility of INOmax in pre-term
neonates. Due to the seriousness of the condition, a randomized
controlled trial cannot be conducted in the pre-term neonate
population.
"Mallinckrodt is extremely pleased
to be able to end this registry based on positive findings much
earlier than anticipated," said Steven
Romano, M.D., Executive Vice President and Chief Scientific
Officer at Mallinckrodt. "The
real-world data provided by this registry underscores our
commitment to continue to expand upon the body of scientific
knowledge on treatment of vulnerable patient populations, such as
premature infants with pulmonary hypertension."
The observational registry study was conducted across 31 sites
and was designed to evaluate the effectiveness and safety of INOmax
in 168 premature neonates vs term and near-term neonates (1:1) with
PH. The interim analysis assessed 54 premature and 84 term and
near-term neonates and demonstrated that the trial achieved the
significance level for non-inferiority. Evaluation of significant
improvement for each neonate is based on at least a 25 percent
decrease in oxygenation index (OI) or surrogate OI (SOI) during the
INOmax treatment period.
No drug-related serious adverse events were attributed to study
drug. At the time of the interim analysis, there were 17 adverse
events of special interest reported in 16 subjects, most of which
were in the preterm group and deemed not related or unlikely
related to study drug.
INOmax has been on the market in the U.S. since 2000 and 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. Please see Important Safety Information below.
About the Observational Registry
- The Registry Evaluating Premature and Term and Near-Term
Neonates with Pulmonary Hypertension Receiving Inhaled Nitric Oxide
(PaTTerN) is a multicenter, prospectively defined,
observational registry study to evaluate the use of INOmax to treat
pulmonary PH in premature neonates (27 to less than 34 weeks
gestational age) and term and near-term neonates (34 to 40 weeks
gestational age).
- The primary outcome measure compares the incidence of subjects
with at least a 25 percent improvement (decrease) from baseline in
OI or SOI during the INOmax treatment period in pre-term vs term
and near-term neonates with PH.
- Secondary efficacy endpoints include:
-
- The incidence of subjects with at least a 25 percent
improvement in OI/SOI in each severity group of mild, moderate and
severe
- The time to response to INOmax up to 96 hours for each severity
and age group
- Evaluation of 25 percent improvement in OI/SOI with univariate
and multivariate logistic regressions for baseline factors: age and
severity group, disease subtype, weight, race, gender
- The incidence of partial responders (< 25 percent
improvement in OI/SOI) and non-responders (< 5 percent
improvement in OI/SOI) summarized by age group and by each severity
group within each age group
- Patients were classified as mild, moderate or severe based on a
primary measure of OI or a secondary measure of SOI for hypoxic
respiratory failure (HRF) severity:
-
- Mild: OI < 16 or SOI < 10
- Moderate: OI value 16 to 25 or SOI value 10 to 15
- Severe: OI >25 or SOI >15
- Patients were evaluated for response to INOmax and safety
during a treatment period of up to 96 hours ± 12 hours and a safety
follow-up through 7 days (for a total of up to 11 days) or to
hospital discharge, whichever came first
More information about the trial can be found here.
Study Limitations
The current study is a prospective observational registry that
collects real world data that describes how INOmax nitric oxide gas
is being used in clinical practice. As an observational study it
does not utilize placebo. Hence, some of the improvement observed
in the current study could be due to factors other than treatment
with INOmax. Similarly, without placebo control it is not possible
to understand the magnitude to which patients who experienced
limited response to inhaled nitric oxide would have otherwise
decompensated without this treatment.
About Persistent Pulmonary Hypertension of the Newborn
(PPHN)
PPHN is a serious and sometimes fatal
cardiorespiratory complication of the transition to extra-uterine
life.1,2 PPHN is a clinical syndrome associated
with various neonatal cardiorespiratory diseases, including
meconium aspiration, respiratory distress syndrome (hyaline
membrane disease), congenital heart disease and congenital
hernia.1 Despite the diversity of causes, marked
pulmonary vasoconstriction is the central pathophysiologic feature
of PPHN.3 The most significant hemodynamic feature in
neonates with severe hypoxia is a pulmonary-to-systemic pressure
imbalance.[4] Treatment in these neonates is directed toward
lowering the pulmonary vascular pressure and supporting the
systemic circulation.1,3
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.
CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING
STATEMENTS
This release includes forward-looking statements
concerning inhaled nitric oxide ("iNO") and the Company's iNO
product, including statements with regard to the clinical data
generated in the study described above. 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: 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
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-2000935 05/20
References
1Nair J, Lakshminrusimha S. Update on PPHM:
Mechanisms and treatment. Semin Perinatol.
2014;38(2):78-91.
2Clark RH. The epidemiology of respiratory failure in
neonates born at an estimated gestational age of 34 weeks or more.
J Perinatol. 2005;25(4):251-257.
3Wedgwood S, Steinhorn RH, Lakshminrushimha S.
Optimal oxygenation and role of free radicals in PPHN. Free
Radical Biology and Medicine. 2019;142:97-106.
4Lakshminrusimha S. The pulmonary circulation in
neonatal respiratory failure. Clin Perinatol.
2012;39(3):655-683.
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