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MNK H.P. Acthar Gel CHART Trial Results Alert

March 28, 2018

MNK H.P. Acthar Gel CHART Trial Results Alert

Since acquiring H.P. Acthar® Gel in 2014, Mallinckrodt has been systematically completing legacy studies that had been initiated by the drug's previous owner. As these studies are concluded, the information gathered is provided to the website ClinicalTrials.gov for posting.

Mallinckrodt has just completed such a process for a small Phase 4 pilot study that was begun by previous owners to generate potential new insights into the use of H.P. Acthar Gel in treatment of idiopathic Membranous Nephropathy (iMN), specifically in refractory patients who had failed previous immunosuppressive therapies.

This underpowered study did not generate data sufficient to reach clinically relevant conclusions. However, clinical experience and additional published data suggest that Acthar is effective at reducing proteinuria across multiple different idiopathic nephrotic syndrome etiologies including iMN, Focal Segmental Glomerular Sclerosis (FSGS), IgA Nephropathy, and Minimal Change Disease (MCD).  In addition, CHART data did reveal durable efficacy as demonstrated by sustained remission through Week 48 in a small subset of patients, consistent with that seen in other datasets. 

Learnings from this study will shape our data generation efforts for Acthar in iMN. We remain committed to making a difference in the lives of these very sick patients, as evidenced by the initiation of the largest FSGS clinical trial ever conducted, as well as fifteen Investigator Initiated research studies developing data on Acthar’s utility across a broad spectrum of nephrotic syndrome etiologies, including recurrent post-transplant FSGS.

Importantly, the study did not generate data sufficient to reach clinically relevant conclusions for the following reasons:

• the understanding of specific factors contributing to disease pathophysiology and treatment evolved during the conduct of the trial, and therefore these factors were not accounted for when the CHART study was being designed,
• hypotheses related to a potential, predicted Acthar treatment effect were based on extremely limited data heavily weighted by experience in treatment-naïve patients – a very different population than the refractory patients targeted here, and
• there were tactical execution challenges – including significant protocol changes and marked differences in underlying disease severity in placebo and Acthar treatment populations.

The company expects the data to be posted on ClinicalTrials.gov over the next days and, when it is, will provide additional updates.

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 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; analgesics and gastrointestinal products. 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.

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CONTACTS
Investor Relations
Daniel J. Speciale, CPA
Investor Relations and Strategy Officer
314-654-3638
daniel.speciale@mnk.com

Media
Rhonda Sciarra
Senior Communications Manager
908-238-6765
rhonda.sciarra@mnk.com

Meredith Fischer
Chief Public Affairs Officer
314-654-3318
meredith.fischer@mnk.com