Mallinckrodt Announces Publication of Real-World Data from Retrospective Study on the Investigational Use of Inhaled Nitric Oxide in Hospitalized COVID-19 Patients

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Apr 13, 2022, 06:45 ET

– Medical chart review study, published in Drugs in Context, evaluated the real-world use of INOmax^® (nitric oxide) gas, for inhalation in hospitalized COVID-19 patients with mild-to-moderate acute respiratory distress syndrome (ARDS) in the U.S. –

DUBLIN, April 13, 2022 /PRNewswire/ -- Mallinckrodt plc (OTCMKTS:MNKKQ), a global biopharmaceutical company, today announced the publication of findings from a retrospective chart review study assessing the real-world use and outcomes of INOmax^® (nitric oxide) gas, for inhalation therapy in hospitalized patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome (ARDS), a disorder in which fluid leaks into the lungs, making breathing difficult or impossible. The results of the study were published in the peer-reviewed journal Drugs in Context.

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.

The safety and efficacy of INOmax to treat COVID-19 have not been evaluated, established or approved for use by the U.S. Food and Drug Administration.

The retrospective, observational medical chart review study included patients who were at least 18 years old at the time of hospitalization, hospitalized for COVID-19, met the Berlin definition of ARDS,¹ received INOmax for at least 24 hours continuously during hospitalization and had a partial pressure of oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ratio (P/F ratio) >100 and ≤300mmHg when INOmax was initiated. A total of 213 patients were screened for enrollment from seven study sites across the U.S. of which 37 patients met enrollment criteria. Patients were followed from COVID-19–related hospitalization up to 30 days post discharge or until loss to follow-up, and data were collected between October 1, 2020, and March 31, 2021. The most common reason for exclusion was severe ARDS with a P/F ratio ≤100 (N=146; 83 percent of excluded patients).²

"These findings of INOmax use in clinical practice may help us gain an understanding of the real-world use of different potential treatment approaches and outcomes in people suffering from mild-to-moderate ARDS, a historically understudied population," said Steve Abman, M.D., lead study investigator and Professor of Pediatrics at the University of Colorado. "In severe cases of COVID-19, ARDS is a major cause of morbidity, making it critical to continue studying this at-risk underserved patient population."

The data analysis found that when response was defined as an increase in P/F ratio by >20 percent at any time after INOmax initiation, nearly two-thirds of patients (n=23; 62.2 percent) achieved response to INOmax. Additionally, mean P/F ratio (standard deviation) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after INOmax initiation (N=34). Median time to response was 3 days (interquartile range 1 to 3 days) after initiation of INOmax. In a sensitivity analysis, when response was defined as a ˃10 percent increase in P/F ratio, most (n=26; 70.3 percent) patients were categorized as responders. Among the 27 patients (73 percent) receiving invasive mechanical ventilation at the time of INOmax initiation, 4 (14.8 percent) were transitioned to non-invasive ventilation. No patient required extracorporeal membrane oxygenation (ECMO) after initiating INOmax. Data on select adverse events of interest were also collected (methemoglobinemia, airway injury and worsening pulmonary edema) and none were attributed to INOmax treatment. At discharge, 20 patients (54 percent) improved or remained stable according to the Clinical Global Impression–Improvement (CGI-I) scores.²

Study limitations include the retrospective nature of the study design and the use of data abstracted from medical charts of study patients. The accuracy and completeness of data in this study are limited by the availability and quality of data in each patient's medical chart. Treatment patterns in the study reflect the use of INOmax for hospitalized COVID-19 patients in selected medical centers willing to participate in this retrospective medical chart study and may not be representative of all institutions using INOmax. The dosing and duration of INOmax treatment was variable across sites and determined at the attending physician's discretion. Criteria for initiation of INOmax, INOmax weaning and weaning protocols were not standardized across sites. Detailed information was not collected about all potential interventions for the acute management of COVID-19 ARDS, including diuretics, vasopressors and prone positioning. Future randomized, placebo-controlled studies are needed to determine potential efficacy, safety and place in therapy. Due to the retrospective nature of this analysis, it is hypothesis-generating; no formal conclusions should be drawn.

"The results of this retrospective medical chart review analysis support the importance of continued collection of real-world data to help expand our understanding of the investigational use and potential of INOmax," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt.

In severe cases, COVID-19 can cause acute respiratory distress syndrome (ARDS), a major cause of morbidity and mortality in patients with COVID-19.^3,4

The study was funded by Mallinckrodt.

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, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; cultured skin substitutes 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 INOmax product, including statements with regard to the potential impact of iNO on patients and anticipated benefits associated with its use. 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.

CONTACT

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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. ©2022 Mallinckrodt. US-2200197 04/22

References

¹ Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. Jun 20 2012;307(23):2526-33. https://doi:10.1001/jama.2012.5669.
² Abman SH, Fox NR, Malik MI, et al. Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome. Drugs in Context. 2022;11:2022-1-4. https://doi.org/10.7573/dic.2022-1-4.
³ Adusumilli NC, Zhang D, Friedman JM, Friedman AJ. Harnessing nitric oxide for preventing, limiting and treating the severe pulmonary consequences of COVID-19. Nitric Oxide. Oct 1 2020;103:4-8. https://doi:10.1016/j.niox.2020.07.003.
⁴ Matthay MA, Aldrich JM, Gotts, JE. Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet Respir Med. 2020. Published Online March 20, 2020. https://doi.org/10.1016/S2213-2600(20)30127-2.