Mallinckrodt Presents New Data from 44-Week Open Label Extension Of Company-Sponsored H.P. Acthar® Gel Trial in Lupus

CHESTERFIELD, United Kingdom, June 9, 2016 /PRNewswire/ -- Researchers for Mallinckrodt plc (NYSE: MNK), a leading specialty biopharmaceutical company, today presented results from the 44-week open label extension (OLE) of its company-sponsored, two-part pilot study exploring the efficacy of H.P. Acthar^® Gel (repository corticotropin injection) (RCI) in Systemic Lupus Erythematosus (SLE) patients with a history of persistently active disease. Acthar is approved by the U.S. Food and Drug Administration for use during an exacerbation or as a maintenance therapy in select patients with SLE. Study data were presented at the European League Against Rheumatism (EULAR) Annual Congress in London.

The open label trial followed the 8-week, double-blind, placebo-controlled randomized phase of the study, results of which can be found on the Mallinckrodt website. All patients completing the first phase of the trial had the opportunity to volunteer to continue to the second phase, and all participants in the 44-week open label phase received Acthar. This included those who received placebo in the initial double-blind phase.

"Taken together, the data from the two phases of this pilot study provide insight into the potential efficacy of Acthar's use as a treatment option in SLE patients who have persistent disease activity despite corticosteroid therapy," said Steven Romano, M.D., Senior Vice President and Chief Scientific Officer, Mallinckrodt. "The findings support the advancement of a well-powered, confirmatory trial in this lupus population, and Mallinckrodt plans to begin this company-sponsored study later this year."

Study Measures, Goals and Outcomes
Standardized disease activity measures were used over the entire 52 weeks of the study to evaluate the effect of RCI on SLE signs and symptoms, such as tender and swollen joints. Mallinckrodt's goal in conducting the open label extension was to explore three primary questions:

• How did study patients treated with RCI in the blinded, 8-week phase of the trial respond after the initial 8 weeks?
• When receiving RCI, did study patients treated with placebo in the blinded, 8-week phase of the trial experience similar results as those patients who received RCI in the blinded phase?
• Did any study patients taper or reduce their steroid use during the 44-week open label study?

Data outcomes from the most recent phase of the study showed that:

• Study patients with persistently active SLE who continued on RCI throughout the 44-week OLE period maintained the reductions achieved in certain measures of disease activity during the blinded phase.
• Study patients who crossed over from placebo to Acthar in the OLE experienced improvements in certain measures of disease activity:
  • By 12-16 weeks after initiating RCI for those patients who received placebo in the double-blind phase of the study, improvements in certain measures of disease activity were generally comparable to the improvements seen in patients who received RCI treatment in the blinded, 8-week phase of the trial.
• Approximately one third of subjects participating in the open label extension were able to taper exogenous corticosteroid dose by at least 50% over the 52 weeks of the study.

"Systemic Lupus Erythematosus is a disease that can be very difficult to manage," said lead investigator Richard A. Furie, M.D., Chief of the Division of Rheumatology, Northwell Health, Great Neck, New York. "It is encouraging to see clinically meaningful, longer-term results from this pilot study of Repository Corticotropin Injection, and I look forward to future data readouts."

Study Limitations
Limitations of this pilot study included the small sample size as well as lack of blinding and lack of a comparator group, both of which are elements associated with an open label design. These results may not be fully representative of outcomes in the overall patient population. Most patients were on multiple therapies. The clinical outcomes may not be solely attributable to Acthar.

Study Details
The Mallinckrodt-sponsored study was titled: "A two-part study exploring the efficacy, safety, and pharmacodynamics of Acthar in systemic lupus erythematosus patients with a history of persistently active disease." Any study patient who completed the 8-week, double-blind, placebo-controlled randomized phase of the study, whether randomized to RCI or placebo, was eligible to enroll in the 44-week open label phase of the study. Of the 38 patients randomized in Phase 1, all 33 patients who completed the initial 8-week pilot study chose to continue in the 44-week OLE phase of the study, with 20 patients completing the full 44 weeks.

The initial Acthar dose in the open label extension study was based on study drug regimen at the completion of the double-blind phase of the trial. Acthar dose adjustment was allowed with the goal of a stable Acthar regimen by week 20, but no later than week 28. Steroid dose adjustment was not allowed until stable Acthar regimen was achieved (weeks 20-28). Steroid taper was encouraged but not required after stable RCI regimen was achieved. Taper of other immunosuppressants was allowed after attempts at steroid taper. There were no unexpected adverse events (AEs). Five of the 33 patients withdrew from the trial due to AEs that were thought to be potentially related to study medication during the open label extension phase.

The abstract and the poster are currently available on the Mallinckrodt website.

About Systemic Lupus Erythematosus
SLE is an autoimmune disease in which the immune system produces antibodies to cells within the body leading to widespread inflammation and tissue damage.¹ It is the most common form of lupus, a condition that impacts at least 1.5 million Americans.² Ninety percent of those diagnosed with lupus are women, often between the ages of 15-44.² Lupus is characterized by periods of illness "flares" and remissions¹ and the disease can affect the joints, skin, brain, lungs, kidneys, and blood vessels. Symptoms may include fatigue, pain or swelling in joints, skin rashes, and fevers.¹

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 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: 
Investor Relations
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Senior Vice President, Investor Strategy and IRO
314-654-6649
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Senior Communications Manager
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Meredith Fischer
Senior Vice President, Communications and Public Affairs
314-654-3318
[email protected]

¹ Systemic lupus erythematosus (SLE or lupus), The Centers for Disease Control and Prevention, Available at: http://www.cdc.gov/arthritis/basics/lupus.htm. Accessed May 31, 2016.
² Lupus Foundation of America Press Kit, About Us. Available at: http://www.lupus.org/about/statistics-on-lupus. Accessed May 31, 2016.

SOURCE Mallinckrodt plc

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