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STAINES-UPON-THAMES, United Kingdom, Dec. 4, 2017 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, announced results from a retrospective, claims-based analysis providing health economic insights on the use of medication and healthcare resource utilization (HCRU) among patients with infantile spasms in the 90 days prior to receipt of H.P. Acthar^® Gel (repository corticotropin injection) therapy. The findings were presented in a poster session at the American Epilepsy Society Annual Meeting, held Dec. 1-5, in Washington, D.C.

"This analysis showed a substantial healthcare burden among all patients with infantile spasms prior to initiation of H.P. Acthar Gel therapy, suggesting a delay in diagnosis or the possible presence of complex seizure types, as well as a delay in receipt of appropriate therapy," said Tunde Otulana, MD, Chief Medical Officer at Mallinckrodt. "Children who develop infantile spasms are at great risk for seizures, autism spectrum disorders, and developmental delays.¹ Therefore, gaining insight into real-world treatment patterns leading up to the use of approved therapy is critical."

Infantile spasms is a rare condition that is often difficult to recognize,² even by physicians. Symptoms may appear similar to other common disorders, which may adversely impact time to diagnosis, receipt of approved therapy and health outcomes.² H.P. Acthar Gel is a first-line monotherapy indicated for the treatment of infantile spasms in infants and children under two years of age.³ Please see Important Safety Information below.

The intended audiences of the study below are population-based decision makers with knowledge and expertise in the area of health care economic analysis and its limitations.

Medication Utilization Patterns Prior to Use of Repository Corticotropin Injection in Patients with Infantile Spasms (AES# 3.279)

Key study highlights include: 

• Antiepileptic drugs were the most frequently dispensed medications (38.3% of patients).
• A substantial mean all-cause HCRU was observed among all patients with infantile spasms in the 90 days prior to initiation of H.P. Acthar Gel therapy, as delineated by the following:
• 11.4 outpatient care visits
• 10.0 non-specialist healthcare provider visits
• 2.5 specialist healthcare provider visits
• 1.0 inpatient/hospital stay
• 0.4 emergency room visits
• 4.2 medications dispensed via pharmacy
• All measures of HCRU, per person per month, generally increased with time and across treatment groups, peaking in the one month prior to initiation of H.P. Acthar Gel.
• The lowest mean all-cause HCRU was seen in patients receiving H.P. Acthar Gel first and patients receiving corticosteroids only, with the latter group having more inpatient/hospital stays (+0.2) and prescription medications (+2.8). The highest mean all-cause HCRU was seen in patients taking multiple classes of medication prior to H.P. Acthar Gel.
• Even the lowest HCRU (i.e., patients receiving H.P. Acthar Gel first) imposed a notable and potentially mitigable healthcare burden, including: 9.5 outpatient care visits; 8.4 non-specialist healthcare provider visits; 1.9 specialist healthcare provider visits; 0.8 inpatient/hospital stays; 0.3 emergency room visits; and 1.9 prescription medications.

"This analysis provides new insights into the impact of potential delays in diagnosis and management of infantile spasms," said Laura Gold, PhD, Primary Investigator and lead author of the study. "These findings underscore the considerable healthcare burden placed on patients with infantile spasms, their caregivers, and the healthcare system."

Study Methodology

• This retrospective analysis used Truven MarketScan^® Commercial Claims and Encounters data from January 1, 2007 to December 31, 2015 and included 462 patients with infantile spasms, with 54% of patients receiving H.P. Acthar Gel first.
• HCRU was measured using medical claims that reflected outpatient care visits by location (office, hospital, or other); outpatient care visits to specialist and non-specialist healthcare providers; inpatient/hospital stays; and emergency room visits. Pharmacy claims were used to measure medication use by drug class: corticosteroids only; Sabril^® (vigabatrin)^4* only; antiepileptic drugs only (excluding Sabril); and multiple drug classes (one or more previously mentioned). Patients who received H.P. Acthar Gel first were classified as having had no prior treatment for infantile spasms.
• Administrative health insurance claims data is collected for reimbursement purposes; it does not typically contain robust clinical detail (e.g., seizure types) or test results.
• MarketScan results may not be generalizable to other populations (e.g., patients with infantile spasms enrolled in other US health plans).
• Prescription use outside of claims and the reasons for use (e.g., diagnoses, events) could not be evaluated. Prescription claims reflect dispensation; utilization is assumed.
• The time interval between diagnosis of infantile spasms and H.P. Acthar Gel initiation could vary. The specific chronology of diagnoses and outcomes pre-index was not evaluated.
• Sample size for some groups was small, complicating conclusions (e.g., nine patients received Sabril^® only, prior to H.P. Acthar Gel). Between group differences were evaluated descriptively.
• By evaluating drug classes for infantile spasms, rather than medications for infantile spasms, the true heterogeneity in medication use is likely underestimated.

Mallinckrodt sponsored the study, which was conducted by researchers from the University of Washington and Mallinckrodt. The poster with additional study details is available on the Mallinckrodt website.

ABOUT INFANTILE SPASMS
Infantile spasms, sometimes called West syndrome, is a rare seizure disorder that occurs in approximately 2,000 to 2,500 infants per year in the U.S., based on a review of population-based studies of the condition.⁵ It most commonly occurs between four and eight months of age.⁶ Early identification, diagnosis, and treatment of infantile spasms are essential to help limit lasting effects.² Children with infantile spasms 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), or a failure to meet developmental milestones.⁷ 

H.P. Acthar Gel (repository corticotropin injection) Indications 
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:

• Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age
• The treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown H.P. 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
• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
• 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)
• The treatment of symptomatic sarcoidosis
• 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)
• 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 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.

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. ©2017 Mallinckrodt ARDUS/01-02/1117/0048 12/17

CONTACTS

Media

Rhonda Sciarra 
Senior Communications Manager 
908-238-6765 
rhonda.sciarra@mallinckrodt.com

Meredith Fischer 
Chief Public Affairs Officer 
314-654-3318 
meredith.fischer@mallinckrodt.com

Investor Relations

Coleman N. Lannum, CFA 
Senior Vice President, Investor Strategy and IRO 
314-654-6649 
cole.lannum@mallinckrodt.com

Daniel J. Speciale, CPA 
Director, Investor Relations 
314-654-3638 
daniel.speciale@mallinckrodt.com

^* Sabril^®, a registered trademark of Lundbeck, is FDA-approved for the treatment of infantile spasms in infants one month to two years of age.

¹ Gold LS, Schepman PB, Wang WJ, et al. Healthcare costs and resource utilization in patients with infantile spasms treated with H.P. Acthar Gel^®. Adv Ther. 2016; 33:1293-1304.
² Child Neurology Foundation. Disorder Directory: Learn from the Experts. Infantile Spasms. http://www.childneurologyfoundation.org/disorders/infantile-spasms/. Accessed November 15, 2017.
³ H.P. Acthar Gel^® (repository corticotropin injection) [package insert]. Hazelwood, MO: Mallinckrodt Pharmaceuticals; 2015. http://www.acthar.com/pdf/acthar-pi.pdf. Accessed November 28, 2017.
⁴ Sabril^® (vigabatrin) [package insert]. Deerfield, IL: Lundbeck; 2017. http://www.lundbeck.com/upload/us/files/pdf/Products/Sabril_PI_US_EN.pdf. Accessed on November 28, 2017.
⁵ Wheless J, Gibson P, Rosbeck K, et al. Infantile spasms (West syndrome): update and resources for pediatricians and providers to share with parents. BMC Pediatrics. 2012;12(1):108. doi:10.1186/1471-2431-12-108. Accessed August 28, 2017.
⁶ Hrachovy R. West's syndrome (infantile spasms). Clinical description and diagnosis. Adv Exp Med Biol. 2002;497:33-50.
⁷ Go CY, Mackay MT, Weiss SK, et al. Evidence-based guideline update: medical treatment of infantile spasms. Neurology. 2012;78:1974-1980.

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