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Retrospective Study on Real-World Treatment Patterns and Outcomes of Acthar® Gel (Repository Corticotropin Injection) in Patients with Refractory Rheumatoid Arthritis Published in Drugs in Context

– Electronic medical chart analysis showed Acthar Gel was associated with clinical improvements and a reduction in prescriptions for concomitant medications in refractory rheumatoid arthritis patients –

DUBLIN – March 28, 2022 –  Mallinckrodt plc, (OTCMKTS: MNKKQ) a global biopharmaceutical company, today announced the publication of findings from a retrospective medical records study assessing the real-world utilization and outcomes of Acthar® Gel (repository corticotropin injection) in patients with refractory rheumatoid arthritis (RA) that did not adequately respond to standard-of-care therapies. The results of the study were published in the peer-reviewed journal Drugs in Context.

Acthar Gel is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides. Acthar Gel is approved by the U.S. Food and Drug Administration (FDA) as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in RA (selected cases may require low-dose maintenance therapy). Please see Important Safety Information for Acthar Gel below.

The study, titled "Real-world Treatment Patterns for Repository Corticotropin Injection in Patients With Rheumatoid Arthritis,” was a descriptive, noninterventional, U.S.-based, retrospective analysis of electronic medical records (EMRs) of 63 patients with refractory RA. Most patients (74.6 percent) were using the recommended Acthar Gel dose of 80 units twice per week for 10.3±6.8 months. This treatment strategy was associated with decreased prescriptions of concomitant medications including glucocorticoids (GCs), non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, as well as improvements in the Clinical Disease Activity Index (CDAI) and patient-reported outcomes (PROs).²

“Real-world evidence is necessary to support the effectiveness of RA drugs in a clinical setting and to identify appropriate patient populations who are likely to experience a clinical response to such treatments,” said Howard Busch, D.O., lead study investigator and founder and president of American Arthritis and Rheumatology Associates (AARA). “Our findings describe the potential benefits treatment with Acthar Gel may provide to patients with refractory, persistently active RA that is more difficult to treat.”

“There is an unmet treatment need for patients with high RA disease activity despite treatment with standard-of-care therapies,” said George J. Wan, Ph.D., M.P.H., Vice President Health Economics and Outcomes Research at Mallinckrodt. "We are encouraged by the results of this study that help support the safety and effectiveness of Acthar Gel for short-term adjunctive treatment of refractory RA.”

About the Study ²
The study objectives were to describe demographic and clinical characteristics of patients with RA pre-initiation of Acthar Gel; to identify patterns of dose changes and discontinuations related to Acthar Gel treatment; and to record any changes in clinical scores, PROs and concomitant medications pre- and post-initiation of Acthar Gel. The study used data derived from the Columbus™ repository of EMRs obtained through BendCare, LLC from approximately 100 rheumatology practices associated with the American Arthritis and Rheumatology Associates.

The EMR data, extracted from October 1, 2015 to May 31, 2020 included diagnoses, current and past medications, lab results, biometric data and all rheumatology visit information. Patients were included if they were ≥18 years of age at the Acthar Gel initiation visit and had ≥2 outpatient RA diagnoses with one or more prescriptions or administration of any disease-modifying antirheumatic drug (DMARD) during the entire study period.

Please note that real-world data may include certain characteristics from the patient population that are not necessarily aligned with the approved patient population reflected in the FDA approved package insert. For example, this analysis included some patients with Osteoporosis. Please note that Acthar Gel carries a contraindication for Osteoporosis.

Key Findings ²

• In the 12 months pre-initiation of Acthar Gel, 42 patients (67 percent) were prescribed GCs. Of these 42 patients, 17 patients (40 percent) were prescribed lower dosing regimens of GCs 12 months post-initiation of Acthar Gel.
• DMARD prescriptions remained relatively stable throughout the study.
• The proportion of patients prescribed opioids (41 percent) or NSAIDs (27 percent) was higher during the 12 months pre-initiation of Acthar Gel than during the 12 months post-initiation of Acthar Gel (29 percent and 19 percent, respectively).
• Twelve months post-initiation of Acthar Gel, a reduction in mean CDAI score (−6.6±11.3) was observed, which exceeded the threshold for a minimum clinically important difference (MCID) previously reported as a decrease of 6.5.
• No significant weight gain was associated with Acthar Gel use in these patients.
• Reductions in CDAI, Routine Assessment of Patient Index Data 3 (RAPID3), physician global assessment, tender joint count (TJC), swollen joint count (SJC) and pain visual analogue scale (VAS) scores were observed 12 months post-initiation of Acthar Gel.
• Two patients (4.3 percent) discontinued use of Acthar Gel due to side effects.

Limitations ²
The study limitations are mostly related to incomplete data in the EMRs and a small subset. Due to the retrospective nature of this analysis, it is hypothesis-generating, and no formal conclusions should be drawn. Prescription patterns ascertained from EMR data are subject to greater uncertainty and because linkage to pharmacy claims data was not available, the study assumed that patients filled their prescriptions over the period of observation unless physicians recorded a stop in treatment. Therefore, categorization of medication use may be underestimated. Inferences based upon the findings described here may be limited to the included population (mostly middle-aged white women) which may constrain generalizations of these results to the larger population with refractory RA. However, this patient demographic is highly represented in both this study, and the overall RA population.

The study was funded by Mallinckrodt.

About Rheumatoid Arthritis
RA is an autoimmune disease.³ It is a chronic condition that causes pain, stiffness and swelling of the joints—all symptoms and signs caused by inflammation.⁴ An estimated 1.5 million U.S. adults are living with RA.⁵ Treatment is aimed at stopping inflammation to put the disease in remission and relieve symptoms.⁴ Nonsteroidal anti-inflammatory drugs are used to ease symptoms whereas glucocorticoids, and non-biologic and biologic DMARDs are used to slow down the disease activity. ⁴

IMPORTANT SAFETY INFORMATION

Contraindications
Acthar is contraindicated:

• For intravenous administration
• In infants under 2 years of age who have suspected congenital infections
• With concomitant administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of Acthar
• In patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, or sensitivity to proteins of porcine origin

Warnings and Precautions

• The adverse effects of Acthar are related primarily to its steroidogenic effects
• Acthar may increase susceptibility to new infection or reactivation of latent infections
• Suppression of the hypothalamic-pituitary-adrenal (HPA) axis may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. During recovery of the adrenal gland patients should be protected from the stress (e.g., trauma or surgery) by the use of corticosteroids. Monitor patients for effects of HPA axis suppression after stopping treatment
• Cushing’s syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms
• Acthar can cause elevation of blood pressure, salt and water retention, and hypokalemia. Monitor blood pressure and sodium and potassium levels
• Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and for a period following discontinuation of therapy
• Acthar can cause gastrointestinal (GI) bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain GI disorders. Monitor for signs of perforation and bleeding
• Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression to psychosis. Existing conditions may be aggravated
• Patients with comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar in patients with diabetes and myasthenia gravis
• Prolonged use of Acthar may produce cataracts, glaucoma, and secondary ocular infections. Monitor for signs and symptoms
• Acthar is immunogenic and prolonged administration of Acthar may increase the risk of hypersensitivity reactions. Cases of anaphylaxis have been reported in the post marketing setting. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH and Acthar activity
• There may be an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver
• Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients
• Decrease in bone density may occur. Bone density should be monitored in patients on long-term therapy

Adverse Reactions

• Commonly reported post marketing adverse reactions for Acthar include injection site reaction, asthenic conditions (including fatigue, malaise, asthenia, and lethargy), fluid retention (including peripheral swelling), insomnia, headache, and blood glucose increased
• The most common adverse reactions for the treatment of infantile spasms (IS) are increased risk of infections, convulsions, hypertension, irritability, and pyrexia. Some patients with IS progress to other forms of seizures; IS sometimes masks these seizures, which may become visible once the clinical spasms from IS resolve

Pregnancy

• Acthar may cause fetal harm when administered to a pregnant woman

Please see full Prescribing Information for additional Important Safety 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 Acthar Gel including its potential impact 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

Media Inquiries
Heather Guzzi
Senior Vice President, Green Room Communications
973-524-4112
hguzzi@greenroompr.com

Investor Relations
Daniel J. Speciale
Global Corporate Controller & Chief Investor Relations Officer
314-654-3638
daniel.speciale@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. ©2022 Mallinckrodt. US-2101499 03/22

References
¹ Acthar® Gel (repository corticotropin injection) [prescribing information]. Mallinckrodt ARD LLC.
² Data on File – Ref-05581. Mallinckrodt Pharmaceuticals.
³ Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Research. 2018;6(15). doi:10.1038/s41413-018-0016-9.
⁴ The National Collaborating Centre for Chronic Conditions (NCC-CC). Rheumatoid Arthritis: National clinical guideline for management and treatment in adults. July 2018:15-18.
⁵ Berube LT, Kiely M, Yazici Y, Woolf K. Diet quality of individuals with rheumatoid arthritis using the healthy eating index (HEI)-2010. Nutrition and Health. 2017;23(1):17-24. doi:10.1177/0260106016688223.