Mallinckrodt Study Shows Acthar® Reduces Disease Activity in Patients with Persistently Active Systemic Lupus Erythematosus

CHESTERFIELD, England, Nov. 9, 2015 /PRNewswire/ -- Data presented yesterday by researchers for Mallinckrodt plc (NYSE: MNK), a leading specialty biopharmaceutical company, suggest that H.P. Acthar^® Gel (repository corticotropin injection) reduces certain measures of disease activity in patients with persistently active Systemic Lupus Erythematosus (SLE) who are receiving corticosteroid therapy. The pilot study data were presented at a poster session during the 2015 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting in San Francisco being held Nov. 7-11, 2015. 

"Acthar demonstrated clinically relevant improvement in signs and symptoms of lupus in patients who need an alternative therapy for persistent symptoms," said Steven Romano, M.D., Senior Vice President and Chief Scientific Officer, Mallinckrodt Pharmaceuticals. "This is one of many studies Mallinckrodt is pursuing related to Acthar. We are encouraged by the results of this small study, and the potential Acthar may hold for patients with persistently active SLE."

Acthar is approved by the U.S. Food and Drug Administration (FDA) for use during an exacerbation or as a maintenance therapy in select patients with SLE. For this pilot study, while certain secondary endpoints of the study showed positive results, the primary endpoint was not met.

"Systemic Lupus Erythematosus can be very difficult to manage, and there is an urgent need for additional treatment options," said lead investigator Richard A. Furie, M.D., Chief of the Division of Rheumatology, Hofstra North Shore LIJ School of Medicine, Great Neck, New York. "These data are important because they offer evidence of the efficacy of Acthar as a treatment alternative for patients with SLE."

Study Details

The company-sponsored study, titled "Repository Corticotropin Injection (H.P. Acthar Gel) Attenuates Disease Activity in Patients with Persistently Active Systemic Lupus Erythematosus (SLE) Requiring Corticosteroids," was an eight-week, double-blind, randomized, placebo-controlled study that assessed the clinical efficacy of repository corticotropin injection (RCI) in 38 patients with persistently active SLE involving skin and/or joints, despite moderate dose corticosteroids.

In the eight-week study, subjects were randomized two-to-one with Acthar vs. placebo to receive RCI 40 units subcutaneously every day, RCI 80 units subcutaneously every other day, or a volume-matched placebo gel. Assigned dosing was maintained for the first four weeks then tapered to a twice weekly maintenance dose over the last four weeks. The primary endpoint explored the effects of RCI on the skin and joint sub-scores of the hybrid SLE Disease Activity Index (hSLEDAI), while secondary objectives evaluated effects on total hSLEDAI, British Isles Lupus Assessment Group-2004 (BILAG), Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity, and tender and swollen 28-joint count scores. A post-hoc exploratory endpoint included the SLE responder index (SRI), a composite measure of disease activity.

An open-label extension of this study, exploring the tolerability, steroid-sparing effects, and impact of Acthar on long-term disease control, is ongoing and near completion.

Primary Endpoint Results

The primary endpoint of response (defined by complete resolution of skin or joint activity by hSLEDAI with no new organ system disease by BILAG) was not met.

Certain Secondary Endpoints Results

The addition of RCI to standard of care led to significant improvement in certain measures of disease activity, including total hSLEDAI score, total BILAG score, CLASI activity score, tender and swollen joint count, and SRI. Mean hSLEDAI scores at baseline were 9.8±2.1, 8.7±2.9, 11.3±3.3, and 10.0±3.3 in the combined placebo, RCI 40, RCI 80, and combined RCI groups, respectively (mean ±SD).

• RCI led to significant improvement in secondary efficacy endpoints compared with placebo, including reduction in total hSLEDAI, BILAG, and CLASI Activity scores, decreased tender and swollen joint count, and increased proportion of subjects achieving response as defined by SRI. Significant improvements in disease activity were seen at weeks six and weeks eight after the initiation of RCI therapy
• There were no significant differences in the incidence of treatment-emergent adverse events between groups.

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. Acthar has not been formally studied in combination with other commonly used therapies for SLE.

The abstract is currently available on the ACR website.

About Systemic Lupus Erythematosus
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 (FDA) for the treatment of 19 indications. Of these 19 indications, the product currently generates substantially all of its net sales from the following on-label indications:

• 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).

The company is also exploring the possibility of developing other on-label indications and the possibility of pursuing FDA approval of additional indications not currently on the Acthar label where there is high unmet medical need. 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.
• Longterm 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 specialty biopharmaceutical and imaging business that develops, manufactures, markets and distributes specialty pharmaceutical products and imaging agents. Areas of focus include therapeutic drugs for autoimmune and rare disease specialty areas like neurology, rheumatology, nephrology and pulmonology; immunotherapy and neonatal respiratory critical care therapies; and analgesics and central nervous system drugs. The company's core strengths include the acquisition and management of highly regulated raw materials; deep regulatory expertise; and specialized chemistry, formulation and manufacturing capabilities. To learn more about Mallinckrodt, visit www.mallinckrodt.com. 

Contacts: 
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Coleman N. Lannum, CFA 
Senior Vice President, Investor Strategy and IRO
314-654-6649
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Rhonda Sciarra
Senior Communications Manager
314-654-8618
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Meredith Fischer
Senior Vice President, Communications and Public Affairs
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[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 Oct. 30, 2015.

[2] Lupus Foundation of America Press Kit, About Us. Available at: http://www.lupus.org/about/statistics-on-lupus. Accessed Oct. 30, 2015.

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