Mallinckrodt and Novoteris Receive Clearance from Health Canada to Start Pilot Trial of High-Dose Inhaled Nitric Oxide Therapy for COVID-19 Infection and Associated Lung Complications
-- Study to investigate antiviral activity and improvement in oxygenation and pulmonary arterial pressure in patients suffering from COVID-19 --
"Inhaled nitric oxide may have an antiviral effect, as well as improve oxygenation and pulmonary arterial pressure in patients suffering from COVID-19," said
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
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
Mallinckrodt is currently working with the
For more information, please visit clinicaltrials.gov.
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.
- 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.
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.
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.
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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
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1 Centers for Disease Control and Prevention Fact Sheet. What you need to know about coronavirus disease 2019 (COVID-19). Available at: https://www.cdc.gov/coronavirus/2019-ncov/communication/factsheets.html. Accessed
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