First Patient Enrolled in Mallinckrodt Phase 4 Trial of H.P. Acthar® Gel (Repository Corticotropin Injection) for Pulmonary Sarcoidosis

STAINES-UPON-THAMES, United Kingdom, Jan. 30, 2018 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, today confirmed enrollment of the first patient in the company's Phase 4, multi-center, randomized, double-blind, placebo-controlled pilot study to further assess the efficacy of H.P. Acthar Gel as a therapy option in patients with pulmonary sarcoidosis.

H.P. Acthar Gel is approved by the U.S. Food and Drug Administration (FDA) for the respiratory condition symptomatic sarcoidosis, one of 19 indications.

"I am pleased that the first patient has been enrolled in this important Phase 4 study, the results of which may potentially provide evidence to further support Acthar as a treatment option in appropriate symptomatic sarcoidosis patients," said Dr. Robert Baughman, M.D., Professor in the Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio¹. "In my experience, a considerable number of sarcoidosis patients can have persistent disease that may not be resolved by first-line treatment."

"The enrollment of the first patient in this study is an important milestone in our further assessment of Acthar's efficacy as a treatment option for sarcoidosis patients," said Tunde Otulana, M.D., Chief Medical Officer at Mallinckrodt. "We believe this exploratory evaluation of the more challenging patients who may still have disease activity after previous therapies can potentially help physicians better understand which individuals may benefit from the drug as a treatment alternative."

Full study details can be found on clinicaltrials.gov.

About the Trial

The Phase 4 clinical study is titled "Pilot Study to Assess the Efficacy and Safety of H.P. Acthar® Gel in Subjects With Pulmonary Sarcoidosis." This is a Phase 4, multicenter, randomized, double-blind, placebo-controlled pilot study evaluating the efficacy and safety of H.P. Acthar Gel in the treatment of pulmonary sarcoidosis. All subjects who meet eligibility criteria – which include a requirement to be receiving prednisone treatment – will be randomly assigned to receive either 1mL (80 units) of H.P. Acthar Gel or 1mL of a matching placebo subcutaneously 2 times/week. Subjects will be assigned to treatment in a 1:1 ratio with up to 50 subjects per arm for a total of up to 100 subjects. Subjects who complete the 24-week randomized, double-blind, placebo-controlled treatment period will be eligible to continue in an optional 24-week open-label extension.

Response will be evaluated by Sarcoidosis Treatment Score (STS) with a time frame of baseline to 24 weeks. STS is an exploratory newly developed composite score that combines the results of pulmonary function tests (forced vital capacity; diffusing capacity of the lungs for carbon monoxide), high-resolution computed tomography, quality of life (King's Sarcoidosis Questionnaire; Fatigue Assessment Scale) and corticosteroid tapering.

Find more information about the trial here on the ClinicalTrials.gov website.

About Symptomatic Sarcoidosis^2,3,4

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. In people with sarcoidosis the immune system overreacts, forming clumps of cells called granulomas that result in inflammation to the body's tissues. The disease can impact any organ, but it most often impacts the lungs, lymph nodes, eyes, and skin. Over 90 percent of people with sarcoidosis will suffer lung problems. Concomitant involvement of organs outside of the lungs is common, occurring in as many as half of all sarcoidosis cases.

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

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. 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
cole.lannum@mallinckrodt.com

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

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

Mallinckrodt, the "M" brandmark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. © 2018 ARDUS/01-13/0118/0002 01/18

¹ Dr. Baughman's association with Mallinckrodt includes research grants support, consulting, and involvement with the speakers' bureau.

² Judson MA. The clinical features of sarcoidosis: a comprehensive review. Clin Rev Allerg Immunol. 2015;49:63-78.

³ Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183:573-581.

⁴ 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 Science+Business Media; 2014:149-186.

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