Summary Review of Clinical and Economic Data on H.P. Acthar® Gel (Repository Corticotropin Injection) Published in Advances in Therapy

STAINES-UPON-THAMES, England, July 31, 2017 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, announced the publication of a company-initiated literature review of clinical and economic data on H.P. Acthar^® Gel (repository corticotropin injection) across seven autoimmune and inflammatory disorders – all approved indications for the product. The evidence supported the use of H.P. Acthar Gel across the indications reviewed, pointing to a reduced need for background medications and lower post-therapy healthcare utilization and medical costs.

The analysis, which summarizes data from the Academy of Managed Care Pharmacy (AMCP) Formulary dossier for H.P. Acthar Gel and includes studies from 1956 to 2016, was published online in the June 28, 2017 issue of Advances in Therapy and titled "Clinical and Economic Evaluation of Repository Corticotropin Injection: A Narrative Literature Review of Treatment Efficacy and Healthcare Resource Utilization for Seven Key Indications." The full article is available here.

The article cites data demonstrating the impact of the product – both clinical and healthcare resource utilization (HCRU) – and includes evidence summarized from 16 published clinical investigations and six HCRU studies performed across the seven indications.

"Mallinckrodt's ongoing commitment to conducting studies of patients who receive H.P. Acthar Gel continues to improve understanding and treatment of autoimmune and inflammatory diseases," said Tunde Otulana, MD, Chief Medical Officer at Mallinckrodt. "The extensive body of clinical and economic data in this important review supports the impact that Acthar has had across the seven evaluated indications for patients, the healthcare system and society for many years." 

The indications addressed in the study are:

• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis/polymyositis (DM/PM);
• Monotherapy for the treatment of infantile spasms (IS) in infants and children under 2 years of age;
• Treatment of acute exacerbations of multiple sclerosis (MS) in adults;
• Inducing a diuresis or a remission of proteinuria in nephrotic syndrome (NS) without uremia of the idiopathic type or that due to lupus erythematosus;
• Adjunctive therapy for short‐term administration (to tide the patient over an acute episode or exacerbation) in rheumatoid arthritis (RA);
• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus (SLE); and
• The treatment of symptomatic sarcoidosis.

H.P. Acthar Gel is U.S. Food and Drug Administration (FDA)-approved for the treatment of 19 autoimmune and inflammatory disorders.¹ In 2010 the label was updated to its current form and approved by the FDA to refine the number of indications, and to recognize inclusion of the approved IS indication.

H.P. Acthar Gel has a wealth of clinical experience in the marketplace. Across the 10 currently promoted indications, data demonstrating the impact of the product has been generated by company-sponsored trials, patient registries, investigator-initiated studies, and health economics and outcomes research (HEOR). Mallinckrodt continues to invest in ongoing data generation, including support for additional company-sponsored and independent clinical trials in marketed and potential new indications, HEOR studies and further investigation to support its mechanism of action.

Over two dozen ongoing clinical trials of H.P. Acthar Gel in the treatment of the approved indications and potential new indications are currently registered in the National Institutes of Health clinical trials database (www.ClinicalTrials.gov). A bibliography of existing H.P. Acthar Gel publications by indication can be found on the company's website.

ABOUT DERMATOMYOSITIS/POLYMYOSITIS
DM/PM are rare inflammatory diseases that cause progressive muscle weakness², usually in the muscles closest to the trunk of the body.³ For instance, muscle weakness associated with PM involves those in the hips, thighs, shoulders, upper arms and neck.⁴ DM also causes skin rashes.⁵ People of all ages can be affected, though it usually occurs between the ages of 40-50 and is more common in women.^5,6

ABOUT INFANTILE SPASMS
IS is a rare seizure disorder that affects approximately 2,500 children in the U.S. every year.⁷ It most commonly occurs between four and eight months of age.⁸ Sometimes called West syndrome, IS demands early identification, diagnosis, and treatment to help limit lasting effects.⁷ 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).⁸

ABOUT MULTIPLE SCLEROSIS
MS is a neurologic disorder that affects the central nervous system (i.e., the brain and spinal cord).⁹ Symptoms can include fatigue, balance/coordination issues, numbness or tingling, vision problems, muscle spasms, tremors and emotional changes. More than eight in 10 people with MS will experience a relapse, or flare-up, that brings new or worsening symptoms.¹⁰

ABOUT PROTEINURIA IN NEPHROTIC SYNDROME 
NS is a collection of symptoms that occur when the blood vessels in the kidney begin to leak excess protein in the urine, a condition called proteinuria. A variety of diseases and underlying disorders damage the kidneys and cause proteinuria in people with NS. These etiologies can include glomerular diseases such as: idiopathic membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, membranoproliferative glomerulonephritis, lupus nephritis, and IgA nephropathy. In these and other related disorders, the glomeruli, or small blood vessels that work as the kidney's filtering system, are damaged.

ABOUT RHEUMATOID ARTHRITIS
RA is an autoimmune disease. It is a chronic condition that causes pain, stiffness, and swelling of the joints – all symptoms caused by inflammation.¹¹ An estimated 1.5 million U.S. adults are living with RA.¹²

ABOUT SYSTEMIC LUPUS ERYTHEMATOSUS
SLE is an autoimmune disease in which the immune system produces antibodies to cells within the body leading to possible inflammation and tissue damage.¹³ It is the most common form of lupus, a condition that impacts an estimated 1.5 million Americans.¹⁴ Ninety percent of those diagnosed with lupus are women, often between the ages of 15-44.¹⁴ Lupus is characterized by periods of illness "flares" and remissions and the disease can affect the joints, skin, brain, lungs, kidneys, and blood vessels.¹³ Symptoms may include fatigue, pain or swelling in joints, skin rashes, and fevers.¹³

ABOUT SYMPTOMATIC SARCOIDOSIS
Sarcoidosis is a challenging, yet treatable, rare multisystem disease. In some cases the symptoms may come and go throughout a lifetime. This is referred to as symptomatic sarcoidosis.¹⁵ In people with sarcoidosis the immune system overreacts, forming clumps of cells called granulomas that result in inflammation to the body's tissues.¹⁵ The disease can impact any organ, but it most often impacts the lungs, lymph nodes, eyes, and skin.¹⁵ Over 90 percent of people with sarcoidosis will suffer lung problems.¹⁵ Concomitant involvement of organs outside of the lungs is common, occurring in as many as half of all sarcoidosis cases.¹⁶

About 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:

• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
• 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
• 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
• 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)

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.
For parents and caregivers of IS patients, please also see Medication Guide.

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

Investor Relations
Coleman N. Lannum, CFA 
Senior Vice President, Investor Strategy and IRO 
314-654-6649 
[email protected]

Daniel J. Speciale, CPA 
Director, Investor Relations 
314-654-3638 
[email protected]

Media
Rhonda Sciarra 
Senior Communications Manager 
908-238-6765 
[email protected]

Meredith Fischer 
Chief Public Affairs Officer 
314-654-3318 
[email protected]

¹ H.P. Acthar® Gel (repository corticotropin injection) [prescribing information]. Mallinckrodt ARD, Inc.
² Types of Myositis. The Myositis Association. Available at: http://www.myositis.org./learn-about-myositis/types-of-myositis. Accessed July 19, 2017.
³ Medline Plus. Myositis. Available at: https://medlineplus.gov/myositis.html. Accessed July 19, 2017.
⁴ Mayo Clinic. Polymyositis. Available at: http://www.mayoclinic.org/diseases-conditions/polymyositis/basics/symptoms/con-20020710. Accessed July 19, 2017.
⁵ Rheumatology Center. About Dermatomyositis and Polymyositis. Available at: https://www.actharrheumatology.com/dermatomyositis-and-polymyositis/about-dermatomyositis-and-polymyositis. Accessed July 19, 2017.
⁶ Bernatsky S, Joseph L, Pineau CA, et al. Estimating the prevalence of polymyositis and dermatomyositis from administrative data: age, sex and regional differences. Ann Rheum Dis. 2009;68:1192-1196.
⁷ Understanding Infantile Spasms. Acthar IS Website. Available at: https://www.actharis.com/what-are-infantile-spasms. Accessed July 19, 2017.
⁸ 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 July 19, 2017.
⁹ Multiple Sclerosis Foundation. Get Educated-Common Questions-Multiple Sclerosis. Available at: https://msfocus.org/Get-Educated/Common-Questions#What is Multiple Sclerosis. Accessed July 21, 2017.
¹⁰ National Multiple Sclerosis Society. Relapsing-remitting MS (RRMS). Available at: http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS. Accessed July 19, 2017.
¹¹ What is RA? ActharRA Web site. Available at: https://www.actharra.com/learn-about-acthar/what-is-ra. Accessed July 19, 2017.
¹² What is Rheumatoid Arthritis? Arthritis Foundation. Available at: http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php. Accessed November 3, 2016.
¹³ Systemic lupus erythematosus (SLE or lupus), The Centers for Disease Control and Prevention, Available at: http://www.cdc.gov/arthritis/basics/lupus.html. Accessed November 3, 2016.
¹⁴ Lupus Foundation of America Press Kit. Statistics on Lupus. Available at: http://www.lupus.org/about/statistics-on-lupus. Accessed July 19, 2017.
¹⁵ What Is Sarcoidosis? Acthar Sarcoidosis website. Available at: http://www.actharsarcoidosis.com/understand-symptomatic-sarcoidosis/overview.html. Accessed July 19, 2017.
¹⁶ About Symptomatic Sarcoidosis. Pulmonary Center for Healthcare Professionals website. Available at: https://www.actharpulmonology.com/about-symptomatic-sarcoidosis. Accessed July 19, 2017.

SOURCE Mallinckrodt plc

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