First Patient Enrolled in Mallinckrodt Phase 4 Trial of H.P. Acthar® Gel for Rare Cause of Nephrotic Syndrome

CHESTERFIELD, United Kingdom, May 17, 2016 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty biopharmaceutical company, today confirmed enrollment of the first patient in the company's Phase 4 clinical study assessing the efficacy of H.P. Acthar^® Gel (repository corticotropin injection) for inducing remission of proteinuria due to treatment-resistant or treatment-intolerant idiopathic focal segmental glomerulosclerosis (FSGS). FSGS is a rare disease that can cause nephrotic syndrome, a serious kidney disorder.

"This study is expected to be the largest controlled FSGS-focused clinical trial conducted to date," said lead investigator James A. Tumlin, M.D., Founder and Medical Director of the Southeast Renal Research Institute. "Patients with the disease who are unable to achieve remission are at risk to eventually experience kidney failure, which may lead some patients to the need for dialysis or a transplant. I am pleased to be working with Mallinckrodt in this important effort to better understand how Acthar may help address this serious unmet need."

Acthar is U.S. Food and Drug Administration (FDA)-approved to induce a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus¹. Clinical experience has shown reduction in proteinuria in multiple glomerular nephropathies, including FSGS^2,3,4.

"Mallinckrodt is committed to providing treatment options where few exist," said Steven Romano, M.D., Chief Scientific Officer and Senior Vice President at Mallinckrodt. "Clinical experience supports the use of Acthar to induce remission of proteinuria in FSGS. We are pleased to enroll the first patient in the PODOCYTE trial to better understand how clinicians may utilize Acthar in the management of proteinuria in this patient population."

About the PODOCYTE Trial
The Phase 4, multicenter, randomized, double-blind, parallel group, placebo-controlled efficacy study is titled, "Treatment of Proteinuria Due to Treatment Resistant or Treatment Intolerant Idiopathic Focal Segmental Glomerulosclerosis: A 2 Part Prospective Study of H.P. Acthar Gel (PODOCYTE)." The primary endpoint of the study is to measure complete and partial remission of proteinuria at week 24 as compared with patients' baseline. As is typical with sizeable rare disease clinical trials, the study is expected to take a number of years.

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

About Nephrotic Syndrome
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.

Proteinuria is one of the most important adverse prognostic factors for progression to end stage renal failure in patients with glomerular disease. One of the goals of treating nephrotic syndrome includes reducing or eliminating proteinuria⁵.

About H.P. Acthar^® Gel (repository corticotropin injection)
H.P. Acthar Gel (repository corticotropin injection), is an injectable drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of 19 indications. Of these 19 indications, including the following on-label indications which are currently promoted:

• Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus.
• Treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar 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.
• As monotherapy for the treatment of infantile spasms in infants and children under 2 years of age.
• Use during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.
• Use during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis).

For more information about Acthar, please visit www.acthar.com. Full prescribing information 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 HPA may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. 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 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 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. 

ABOUT MALLINCKRODT
Mallinckrodt is a global business that develops, manufactures, markets and distributes specialty pharmaceutical and biopharmaceutical products and therapies, as well as nuclear imaging products. Areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology and pulmonology; immunotherapy and neonatal respiratory critical care therapies; analgesics and hemostasis products; and central nervous system drugs. 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; its Specialty Generics segment includes specialty generic drugs, active pharmaceutical ingredients and external manufacturing; and the Nuclear Imaging segment includes nuclear imaging agents. 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 Communications Manager
314-654-8618
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Meredith Fischer
Senior Vice President, Communications and Public Affairs
314-654-3318
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Investor Relations
Coleman N. Lannum, CFA
Senior Vice President, Investor Strategy and IRO
314-654-6649
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¹ H.P. Acthar® Gel (repository corticotropin injection) [prescribing information]. Mallinckrodt ARD, Inc.
² Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36:58-67.
³ Hogan J, Bomback AS, Mehta K, et al. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013;8(12):2072-2081.
⁴ Bomback AS, Tumlin JA, Baranski J, et al. Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel. Drug Des Devel Ther. 2011;5:147-153.
⁵ Troyanov et al. J Am Soc Nephrol. 2005;16(4):1061–1068.

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