Positive Outcomes With H.P. Acthar Gel In Proteinuria In Nephrotic Syndrome Reported At National Kidney Foundation Spring Congress

DALLAS, March 27, 2015 /PRNewswire/ -- Mallinckrodt (NYSE: MNK) today reported two separate presentations by independent¹ physicians of real-world cases demonstrating positive outcomes with H.P. Acthar^® Gel (repository corticotropin injection) in the remission of proteinuria, or excess protein in the urine, due to nephrotic syndrome (NS) associated with certain rare but serious kidney disorders. The physicians presented their findings at the 2015 Spring Clinical Meetings of the National Kidney Foundation (NKF), March 25-29.

“The National Kidney Foundation was founded as an advocacy organization to promote research to help children with nephrotic syndrome,” said Kerry Willis, Ph.D, Chief Scientific Officer, National Kidney Foundation. “We are gratified that advancements continue to be made in this critical area of unmet need for patients of all ages.”

The first presentation on a retrospective case series included outcomes of nine patients from different medical practices diagnosed with IgA nephropathy, membranous lupus nephritis or minimal change disease. After treatment with Acthar for at least six months, nearly 80 percent (7/9) of the patients showed proteinuria reduction of 30 percent or more from baseline, ranging from 36.4 percent to 99.4 percent. Two patients had a complete response, four had a partial response, and one had a clinically meaningful response, as measured by criteria from the American Society of Nephrology. Treatment with Acthar was well tolerated; one patient had an early termination of treatment due to weight gain and hypertension.

“There is a tremendous need for additional therapeutic options for treatment-resistant nephrotic syndrome,” said Anupa Khastgir, M.D., a nephrologist in private practice in Oklahoma City, Okla., who presented the case series. “In this case series, Acthar was shown to produce clinically meaningful reductions in proteinuria in this diverse group of patients, several of whom had failed at least one prior therapy for nephrotic syndrome.”

The nine patients were the latest additions to a larger retrospective case series of 44 Acthar-treated patients submitted by physicians around the country.² Dr. Khastgir’s findings of similar outcomes in the series from 13 other patients with NS due to various underlying disorders were recently presented at the International Society of Nephrology World Congress of Nephrology, held March 13-17, 2015, in Cape Town, South Africa. In nine of the 13 patients who completed at least six months of treatment with Acthar, 66.7 percent (6/9) showed proteinuria reduction of 37 percent or greater, with a range of proteinuria reduction from 37.3 percent to 99.4 percent. One patient showed a complete remission of proteinuria, four showed partial remission, and one had a clinically meaningful response. Three patients had early termination of treatment due to side effects, including increased swelling, weight gain, and hypertension.

Separately at the NKF meeting, a case review of a patient with the extremely rare kidney disorder fibrillary glomerulonephritis (FGN) with advanced kidney failure was presented. After eight weeks of treatment with Acthar, the patient achieved partial remission as measured by the study criteria. According to the author’s conclusions:

• The patient achieved partial remission of proteinuria,
• The treatment was well-tolerated with only mild cushingoid side effects, and
• This case study suggests Acthar Gel may help meet an important treatment need in FGN, a subtype of NS.

“There are no randomized, controlled trials to inform treatment decisions for patients with idiopathic FGN, and retrospective studies have not shown significant benefit from a variety of immunosuppressive therapies,” said Dmitri Vasin, M.D., of Renal Remission and Hypertension Consultants in Silverdale, Wash., who treated the FGN patient. “FGN is a rare but extremely serious diagnosis, and I’m eager to share with fellow clinicians my patient’s response to treatment with Acthar.”

About Nephrotic Syndrome
Nephrotic syndrome (NS) is a collection of symptoms that occur when the blood vessels in the kidney begin to leak. This results in proteinuria, a condition which allows protein to leave the body through the urine in large amounts. A variety of diseases and underlying disorders damage the kidneys and cause proteinuria in people with NS. These can include: membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, membranoproliferative glomerulonephritis, lupus nephritis, and IgA nephropathy. In these and other related diseases, 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 chronic renal disease. One of the main goals of treating nephrotic syndrome is to reduce or eliminate proteinuria.³

About the National Kidney Foundation
The National Kidney Foundation is the leading organization in the U.S. dedicated to the awareness, prevention and treatment of kidney disease for hundreds of thousands of healthcare professionals, millions of patients and their families, and tens of millions of Americans at risk. For more information, visit www.kidney.org.

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: the treatment of proteinuria in the nephrotic syndrome of the idiopathic type (NS), the treatment of acute exacerbations of multiple sclerosis (MS) in adults, the treatment of infantile spasms (IS) in infants and children under two years of age, and the treatment of certain rheumatology related conditions, including the treatment of the rare and closely related neuromuscular disorders dermatomyositis and polymyositis. With respect to nephrotic syndrome, the FDA has approved Acthar to “induce a diuresis or a remission of proteinuria in the nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus.” 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.

IMPORTANT RISK INFORMATION

Indication: H.P. Acthar Gel is repository corticotropin injection currently approved by the FDA for 19 indications in four key, hard-to-treat areas: acute exacerbations of multiple sclerosis; proteinuria in ideopathic types of nephrotic syndrome; infantile spasms in children under 2 years old; and rheumatology-related conditions such as polymyositis and dermatomyositis.

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.

Warning 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, 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 additional important safety information.

For patients, parents and caregivers, please also see Medication Guide.

About Mallinckrodt
Mallinckrodt is a global specialty biopharmaceutical and medical imaging business that develops, manufactures, markets and distributes specialty pharmaceutical products and medical imaging agents. Areas of focus include therapeutic drugs for autoimmune and rare disease specialty areas like neurology, rheumatology, nephrology and pulmonology along with analgesics and central nervous system drugs for prescribing by office- and hospital-based physicians. 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. 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 Global Medical Imaging segment includes contrast media and nuclear imaging agents. Mallinckrodt has approximately 5,500 employees worldwide and a commercial presence in roughly 65 countries. The company’s fiscal 2014 revenue totaled $2.54 billion. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Contacts:
Media
Rhonda Sciarra
Manager, Communications
314.654.8618
rhonda.sciarra@mallinckrodt.com

Meredith Fischer
Senior Vice President, Communications
314.654.3318
meredith.fischer@mallinckrodt.com

Investors
Cole Lannum: 314-654-6649; cole.lannum@mallinckrodt.com
John Moten: 314-654-6650; john.moten@mallinckrodt.com

¹ Funding for development, editorial, design and production for all referenced studies was provided by Mallinckrodt Pharmaceuticals to MedVal Scientific Information Services, LLC, Skillman, NJ, USA.
² Treatment of Nephrotic Syndrome with Acthar^® Gel: A Retrospective Case Series; Madan, Milward,Teehan, Mijovic-Das, Khastgir. Presented at the National Kidney Foundation (NKF) 2014 Spring Clinical Meetings, April 22-26, 2014, Las Vegas, Nevada.
³ National Institutes of Health, National Library of Medicine. Nephrotic syndrome in adults. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394708/. Accessed March 26, 2015.

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