Mallinckrodt Data from New Company-Sponsored Studies Presented at American Academy of Neurology 69th Annual Meeting

STAINES-UPON-THAMES, United Kingdom, April 28, 2017 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, announced new results from two company-sponsored studies: one study on use of H.P. Acthar^® Gel (repository corticotropin injection) in patients with infantile spasms (IS) and a second study on the economic burden of moderate-to-severe multiple sclerosis (MS) relapse. Findings from the IS study indicate treatment with H.P. Acthar Gel may be associated with a decline in medical resource utilization (MRU) in the three months following treatment completion, including the number of emergency room (ER) visits, hospitalizations and days hospitalized. Results from the MS study indicate the economic burden of moderate-to-severe MS relapse is underestimated within the scientific literature in terms of frequency, duration and impact, thereby underscoring an unmet need in appropriate assessment and treatment of relapse. These results were presented Tuesday, Apr. 25, 2017 at the American Academy of Neurology (AAN) 69^th Annual Meeting in Boston, Mass.

"Mallinckrodt continues to build on the knowledge surrounding IS and MS relapse, two disease categories for which Acthar is an important treatment option," said Tunde Otulana, Chief Medical Officer at Mallinckrodt. "We are committed to further demonstrating the overall value of Acthar to appropriate patients."

H.P. Acthar Gel has been approved by the U.S. Food and Drug Administration (FDA) as a first line monotherapy treatment for IS since 2010.¹ It has also been approved by the FDA to treat MS relapse since 1978[2] and is proven to help speed its relief.² However, there is no evidence that H.P. Acthar Gel affects the ultimate outcome or natural history of multiple sclerosis.

Medical Resource Utilization in Patients with Infantile Spasms after Receipt of Repository Corticotropin Injection (H.P. Acthar Gel): Results of a Physician Survey assessed characteristics of treating physicians and their practices, and treating physicians' patients with IS and their MRU. Physicians were identified using a national list of H.P. Acthar Gel prescribers and the American Medical Association (AMA) Physician Masterfile. Physicians must have treated patients with H.P. Acthar Gel between three months and two years prior to study enrollment and were required to have complete medical charts available. 

Key highlights include:

• A total of 101 physicians (68 neurologists; 33 internal medicine physicians) and 159 patients were reflected in the survey. The top underlying causes of IS in patients included tuberous sclerosis (21 patients), other genetic abnormalities (17 patients), and central nervous system infections (14 patients).
• There was a statistically significant decrease in the number of ER visits (-0.35; 21 percent reduction) and hospitalizations (-0.33; 20 percent reduction) in the three months after completing treatment with H.P. Acthar Gel (all p ≤ 0.02). Among those hospitalized, there was a decrease in the number of direct admissions (-0.11; 12 percent reduction), admissions through the ER (-0.22; 28 percent reduction), and days hospitalized (-1.32; 54 percent reduction).
• A non-significant decrease (-0.28; 10 percent reduction) in outpatient visits was also reported.
• The average age of patients with IS in the survey was eight months. Approximately one-third were female and about half were Caucasian.

Limitations

Exclusive use of H.P. Acthar Gel was not mandated, and simultaneous use of other agents was not examined. Therefore, observed MRU reductions may not be attributable solely to H.P. Acthar Gel.

The poster is available on the Mallinckrodt website.

The Economic Burden of Moderate-to-Severe Multiple Sclerosis Relapse in the United States: Findings from a Systematic Literature Review examined the scientific literature to characterize the economic burden of moderate-to-severe MS relapse. No date restrictions were placed on direct cost studies; indirect cost studies were searched back to 2010. Relapse treatment was required to be mentioned. Of 4,263 English-language, full-text search results, 24 studies discussed economic burden; of these 24 studies, four studies addressed relapse severity, each using different study designs, cost components, and/or patient types. Key studies could not be further integrated due to inherent differences.

Key highlights include:

• The majority of studies do not address nor differentiate severity. The few studies that do, indicate the cost and impact of relapse increases with relapse severity.
• Two notable studies are those from O'Brien et al., 2003³, and Parisé et al., 2013⁴:
• O'Brien et al. reported 90-day direct costs per relapse of high- and moderate-intensity management of $12,870 and $1,847, respectively [2016 amount: $21,544 and $3,092]³;
• Parisé et al. reported one-year mean MS-related direct costs per patient of high- and low-to-moderate severity relapse of $29,355 and $18,981, respectively [2016 amount: $33,961 and $21,959]⁴;
• Parisé et al. reported spouse caregiver burden by relapse frequency, not severity.⁴
• Notably, effects of MS-relapse severity on patient functioning and disability, caregiver burden, and relapse duration are difficult to measure, incorporate, and translate into overall burden, and are not well addressed in the literature.
• The burden of moderate-to-severe relapse remains underappreciated and an unmet need in understanding MS relapse still exists. Implications for relapse awareness, characterization and management should be considered.

Limitations

The few studies which met the criteria in the literature search used varying designs, relapse definitions, durations and metrics, complicating synthesis and interpretation of results. 

The poster is available on the Mallinckrodt website.

ABOUT INFANTILE SPASMS

IS is a rare seizure disorder that affects approximately 2,500 children in the U.S. every year.⁵ It most commonly occurs between four and eight months of age.⁶ Sometimes called West syndrome, IS demands early identification, diagnosis, and treatment to help limit lasting effects.⁵ Children with IS generally have one or more of the following symptoms: a certain type of seizure (called "spasms"), a disorganized and chaotic brain-wave pattern called hypsarrhythmia as recorded on an EEG (electroencephalogram).⁶

ABOUT MULTIPLE SCLEROSIS (MS)

MS is a neurologic disorder that affects the central nervous system (i.e., the brain and spinal cord).⁷ Symptoms can include fatigue, balance/coordination issues, numbness or tingling, vision problems, muscle spasms, tremors and emotional changes.7 More than eight in 10 people with MS will experience a relapse, or flare-up, that brings new or worsening symptoms.⁸  

About H.P. Acthar^® Gel (repository corticotropin injection)

H.P. 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:

• As an orphan monotherapy medication for the treatment of IS in infants and children under 2 years of age.
• Treatment of acute exacerbations of multiple sclerosis in adults.

For more information about Acthar, please visit www.acthar.com. The Full Prescribing Information may be accessed here. The Medication Guide that provides information about the use of H.P. Acthar Gel for the treatment of Infantile Spasms may be accessed here.

Important Safety Information

• 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.
• 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 suppression after stopping treatment.
• Cushing's Syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms.
• Monitor patients for elevation of blood pressure, salt and water retention, and hypokalemia.
• Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and following discontinuation.
• Acthar can cause gastrointestinal (GI) bleeding and gastric ulcer with an increased risk for perforation with certain GI disorders. Monitor for signs of bleeding.
• Acthar may be associated with central nervous system (CNS) effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, depression, and psychosis.  Existing conditions may be aggravated.
• Patients with comorbid disease may have that disease worsened. Caution should be used in patients with diabetes and myasthenia gravis.
• Prolonged use of Acthar may produce cataracts, glaucoma and secondary ocular infections.
• Acthar is immunogenic and prolonged use may increase the risk of hypersensitivity reactions.
• There is an enhanced effect in patients with hypothyroidism and those with cirrhosis of liver.
• Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients.
• Decrease in bone density may occur. Monitor during 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.
• Common adverse reactions 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.

Please see full Prescribing Information here for additional Important Safety Information. The Medication Guide that provides information about the use of H.P. Acthar Gel for the treatment of Infantile Spasms may be accessed here.

ABOUT MALLINCKRODT

Mallinckrodt is a global business that develops, manufactures, markets and distributes specialty pharmaceutical products and therapies. 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; and analgesics and hemostasis products. The company's core strengths include the acquisition and management of highly regulated raw materials and specialized chemistry, formulation and manufacturing capabilities. The company's Specialty Brands segment includes branded medicines and its Specialty Generics segment includes specialty generic drugs, active pharmaceutical ingredients and external manufacturing. 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.

CONTACTS

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Senior Vice President, Investor Strategy and IRO 
314-654-6649 
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Daniel J. Speciale, CPA 
Director, Investor Relations 
314-654-3638 
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Meredith Fischer 
Chief Public Affairs Officer 
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¹ Acthar Prescribing Information. 8.4 Pediatric Use. Available at: http://www.acthar.com/pdf/Acthar-PI.pdf. Accessed April 10, 2017.

² Why Acthar for MS Relapse. ActharMSRelapse Website. Available at: https://msfocus.org/Get-Educated/Common-Questions#What is Multiple Sclerosis. Accessed April 6, 2017.

³ O'Brien JA et al. Cost of managing an episode of relapse in multiple sclerosis in the United States. BMC Health Services Research. 2003;3(1):17 Available at: https://bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-3-17. Accessed April 21, 2017.

⁴ Parisé H et al. Direct and indirect cost burden associated with multiple sclerosis relapses: excess costs of persons with MS and their spouse caregivers. Journal of the Neurological Sciences. 2013;330(1-2):71-7 Available at: https://www.ncbi.nlm.nih.gov/pubmed/23647840. Accessed April 21, 2017.

⁵ Understanding Infantile Spasms. ActharIS Website. Available at: https://www.actharis.com/what-are-infantile-spasms. Accessed April 6, 2017.

⁶ Parent and Caregiver Brochure - Acthar for Infantile Spasms: Commonly asked questions about treatment, Mallinckrodt Website, p. 2. Available at: https://www.actharis.com/docs/acthar-infantile-spasms-brochure.pdf. Accessed March 24, 2017.

⁷ Multiple Sclerosis Foundation. Symptoms of Multiple Sclerosis. Available at: http://msfocus.org/Symptoms-of-Multiple-Sclerosis.aspx. Accessed April 19, 2017.

⁸ National Multiple Sclerosis Society. Relapsing-remitting MS (RRMS). Available at: http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS. Accessed April 21, 2017

SOURCE Mallinckrodt plc

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