Mallinckrodt Enrolls First Patient in Phase 2B Trial of H.P. Acthar® Gel (Repository Corticotropin Injection) for Amyotrophic Lateral Sclerosis (ALS)

STAINES-UPON-THAMES, United Kingdom, June 14, 2017/PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, today confirmed enrollment of the first patient in the company's Phase 2B study designed to assess the efficacy and safety of H.P. Acthar^® Gel (repository corticotropin injection) as a treatment for amyotrophic lateral sclerosis (ALS).

The U.S. Food and Drug Administration (FDA) previously granted the company's request for a Fast Track designation and orphan status for its H.P. Acthar Gel Investigational New Drug application in patients with ALS. The drug is not FDA-approved for the ALS indication.

"ALS is a rare and incurable disorder that impacts patients from all walks of life," said Todd Levine, M.D., founder and director of the Phoenix Neurological ALS Clinic and adjunct Professor of Neurology at Kansas University. "The community welcomes new research aimed at further understanding the disease and potential new treatments for ALS."

"We are pleased to announce the first patient in this important study of Acthar in ALS patients," said Steven Romano, M.D., Chief Scientific Officer and Executive Vice President at Mallinckrodt. "This multi-center, double blind, placebo-controlled trial will evaluate the effects of the drug on established measures of disease symptoms and progression, enabling us to assess the potential value Acthar may bring to patients with this devastating disease."

About the PENNANT Trial
The Phase 2B clinical study is titled "A Multicenter, Double Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of H.P. Acthar Gel in the Treatment of Subjects with Amyotrophic Lateral Sclerosis." The study will enroll patients ages 18 to 75 with ALS and symptom onset (defined as first muscle weakness or dysarthria) ≤ two years prior to the screening visit. Subjects will be randomized on a 2:1 basis to receive subcutaneous (SC) H.P. Acthar Gel 0.2 mL (16 units) daily or SC matching placebo 0.2 mL daily for 36 weeks.

The efficacy of H.P. Acthar Gel will be assessed using standard measures of functional decline, including change from baseline in the ALS Functional Rating Scale-Revised, assessed after 36 weeks of therapy. Approximately 195 patients will be enrolled across multiple sites.

Find more information about the Pennant trial hereon the ClinicalTrials.gov website.

About ALS
ALS is a progressive neurodegenerative disease that affects motor neuron cells in the brain and the spinal cord. Motor neurons reach from the brain and the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their demise and when the motor neurons die, voluntary and involuntary muscle movement is lost. With the progressive loss of motor neurons, people with ALS may lose the ability to speak, eat, move and breathe.

There is increasing evidence that neuro-inflammation accompanies the death of motor neurons in ALS.  Several inflammatory events that appear to accompany disease progression in ALS might be amenable to pharmacologic interventions as a component of disease management, and research in the field is investigating new approaches to implement an anti-inflammatory strategy for treating ALS¹.

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 H.P. Acthar Gel use is in these indications:

• As an orphan monotherapy medication for the treatment of infantile spasms (IS) in infants and children under 2 years of age.
• 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.
• 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).
• Use as adjunct therapy for short-term administration in psoriatic arthritis; rheumatoid arthritis, juvenile rheumatoid arthritis and ankylosing spondylitis to tide patients over an acute episode or exacerbation.
• Treatment of symptomatic sarcoidosis.
• 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.

For more information about Acthar, please visit www.acthar.com. Please click to see full Prescribing Information and Medication Guide.

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 adrenal (HPA) axis 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 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.

Adverse Reactions

• 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 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
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

¹ The ALS Association, Our Research, Focus Areas, Disease Mechanisms. http://www.alsa.org/research/focus-areas/disease-mechanisms/ Accessed May 22, 2017.

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SOURCE Mallinckrodt plc