Data on Acthar® Gel (Repository Corticotropin Injection) Therapy in Symptomatic Sarcoidosis Published in Therapeutic Advances in Respiratory Disease

STAINES-UPON-THAMES, United Kingdom, Nov. 26, 2019 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a global biopharmaceutical company, today announced findings from a large retrospective study of Acthar^® Gel (repository corticotropin injection) in the treatment of the respiratory disease symptomatic sarcoidosis that assessed patient characteristics, treatment patterns, concomitant medication use and physicians' assessments of treatment response. The study examined medical records from 302 patients with advanced symptomatic sarcoidosis, the majority of whom had comorbidities and had previously been treated with corticosteroids. The analysis showed that the use of Acthar Gel was associated with improved overall health status in 95 percent of patients as reported by physicians' assessments, with more than half of patients (54 percent) seeing improvements in two or more symptoms. In addition, there was an association observed between the use of Acthar Gel therapy and reduced overall use of other medications. Results of the study were recently published online in Therapeutic Advances in Respiratory Disease, an online, open-access peer-reviewed journal.

Acthar Gel is approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptomatic sarcoidosis.¹ Please see Important Safety Information for Acthar Gel below.

"Symptomatic sarcoidosis is a rare and clinically challenging multisystem disease^2,3 with high-dose corticosteroids as the mainstay of therapy. Mallinckrodt is committed to better understanding patients who may need an alternative to corticosteroids," said George Wan, Ph.D., Vice President and Global Head of Health Economics and Outcomes Research at Mallinckrodt. "This study examined records from a large group of patients with advanced symptomatic sarcoidosis, and as such provides real-world data to support the use of Acthar Gel therapy in clinical practice in appropriate patients."

The study, titled "Repository corticotropin injection in patients with advanced symptomatic sarcoidosis: retrospective analysis of medical records," evaluated patient records from 302 adult (≥18, mean age=51 years) patients who were treated with Acthar Gel in the previous 36 months at the time of data collection from September 2017 to November 2017.

Study Methods

Patients were required to have completed an individualized course of Acthar Gel therapy or received Acthar Gel for ≥6 months at the time of data collection. Records were analyzed from 98 physicians in a range of specialties, including pulmonology, rheumatology, primary care, dermatology, cardiology, ophthalmology, gastroenterology and neurology.

• Sixty-four percent of patients had chest imaging and biopsy-confirmed stage 3 or 4 sarcoidosis and 30 percent had been hospitalized for sarcoidosis during the previous year.
• All patients had evidence of pulmonary involvement; 42 percent had involvement of one extrapulmonary organ and 34 percent had involvement in multiple extrapulmonary organs, most commonly the skin (28 percent), joints (25 percent), heart (22 percent) and eyes (22 percent).
• Patients' symptoms included mild-to-moderate shortness of breath, fatigue, bone and joint pain, wheezing/coughing and abnormal heartbeat prior to treatment with Acthar Gel.
• 76% of patients reported 1 or more comorbidities; 24 percent had no comorbid conditions.
• The study examined concurrent medication use before, during and after Acthar Gel therapy. Eighty-six percent of patients had received other treatments in the three months prior to receiving Acthar Gel and concurrent medications used included oral corticosteroids, biologics, immunosuppressants and antimalarial agents.

Additional Observations

The analysis found that patients had varied and individualized dosing regimens. The mean duration of Acthar Gel treatment was 32.5 weeks, with 61.6 percent of patients continuing treatment for ≥6 months.

• Use of Acthar Gel was associated with a reduction in the use of other medications.
• Acthar Gel was also associated with an overall decrease in use of corticosteroids from 61.3 percent during the three months before Acthar Gel initiation to 12.9 percent three months after the start of Acthar Gel therapy.
• The analysis also showed an association between Acthar Gel treatment and a decrease in the mean daily dose of corticosteroids from 18.2 mg to 9.9 mg.

According to physicians' assessments of change in patient health status following Acthar Gel therapy, improvements were reported in: overall health status (95 percent) as measured by the question "What is the patient's status as of the end of RCI therapy or the six months point in therapy for ongoing treatment patients?" In addition, physicians reported overall reduced symptoms (73 percent); improved lung function (38 percent); reduced inflammation (33 percent); reduction or discontinuation of corticosteroids (32 percent); and increased quality of life (32 percent).

Limitations

• The study's retrospective design is limited by data collected from patient medical records that could have errors or omissions. Outcomes may be influenced by therapies not documented in the chart.
• Most patients were on multiple therapies; the clinical outcomes may not be solely attributable to Acthar Gel.
• There is an inherent risk of bias resulting in overestimation of the effectiveness of Acthar Gel based on a subjective endpoint such as physicians' assessments.
• As with any retrospective design, data are exploratory and hypothesis-generating and comparisons between Acthar Gel and control groups or other treatments cannot be made.
• The study did not capture adverse reactions in this cohort of patients with symptomatic sarcoidosis.

The analysis was conducted by Mallinckrodt.  The company is also currently conducting a Phase 4, multicenter, randomized, double-blind, placebo-controlled pilot study evaluating the efficacy and safety of Acthar Gel in the treatment of pulmonary sarcoidosis. Read more at: https://clinicaltrials.gov/ct2/show/NCT03320070.

About Sarcoidosis
Sarcoidosis is a challenging, yet manageable, rare multisystem disease.^2,3 In some cases the symptoms may come and go throughout a lifetime. This is referred to as symptomatic sarcoidosis. In people with sarcoidosis, the immune system overreacts, forming clumps of cells called granulomas that result in inflammation to the body's tissues.⁴ The disease can impact any organ, but it most often impacts the lungs, lymph nodes, eyes, and skin.² Over 90 percent of people with sarcoidosis suffer lung problems.⁴ Concomitant involvement of organs outside of the lungs is common, occurring in as many as half of all sarcoidosis cases.⁵

Acthar Gel (repository corticotropin injection) Indications
Acthar Gel is an injectable drug approved by the FDA for the treatment of 19 indications. Of these, today the majority of Acthar use is in these indications:

• Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy)
• The treatment of symptomatic sarcoidosis
• Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age
• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
• The treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar Gel to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease
• Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus
• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis)
• Treatment of severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation

IMPORTANT SAFETY INFORMATION

Contraindications

• Acthar should never be administered intravenously
• Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar
• Acthar is contraindicated where congenital infections are suspected in infants
• Acthar is contraindicated 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 origins

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-axis (HPA) 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 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. Blood pressure, sodium and potassium levels may need to be monitored
• 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 GI bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain gastrointestinal disorders. Monitor for signs of bleeding
• Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression, and 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. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH activity
• There is 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 for patients on long-term therapy
• Pregnancy Class C: Acthar has been shown to have an embryocidal effect and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

Adverse Reactions

• Common adverse reactions for Acthar are similar to those of corticosteroids and include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain
• Specific adverse reactions reported in IS clinical trials in infants and children under 2 years of age included: infection, hypertension, irritability, Cushingoid symptoms, constipation, diarrhea, vomiting, pyrexia, weight gain, increased appetite, decreased appetite, nasal congestion, acne, rash, and cardiac hypertrophy. Convulsions were also reported, but these may actually be occurring because some IS patients progress to other forms of seizures and IS sometimes mask other seizures, which become visible once the clinical spasms from IS resolve

Other adverse events reported are included in the full Prescribing Information.

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 Acthar Gel including expectations regarding related clinical trials, 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.

CONTACTS
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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. ©2019 Mallinckrodt. US-1901951 11/19

References

¹ Acthar^® Gel (repository corticotropin injection) [prescribing information]. Mallinckrodt ARD, Inc.
² Judson MA. The clinical features of sarcoidosis: a comprehensive review. Clin Rev Allerg Immunol. 2015;49:63-78.
³ Boughman 2016 Baughman RP, Field S, Costabel U, et al. Sarcoidosis in America. Analysis based on health care use. Ann Am Thorac Soc 2016;13:1244-1252.
⁴ Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183:573-581.
⁵ Shigemitsu H, Patel HV, Schreiber MP. Extrapulmonary sarcoidosis. In: Judson MA, ed. Pulmonary Sarcoidosis: A Guide for the Practicing Clinician. Vol 17. New York, NY: Springer; 2014:149-186.

SOURCE Mallinckrodt plc

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