Mallinckrodt Announces Positive Top-Line Findings from its Observational Registry Assessing Relapse Recovery in Multiple Sclerosis Relapse Patients Treated with Acthar® Gel (Repository Corticotropin Injection)

STAINES-UPON-THAMES, United Kingdom, Oct. 1, 2019 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a global biopharmaceutical company, today announced positive top-line findings from its observational registry to assess treatment patterns and response to Acthar^® Gel (repository corticotropin injection) in reducing the clinical impact of disease exacerbations in patients with multiple sclerosis (MS) relapse. The results for the main subsets of patients are highly statistically significant for all the efficacy endpoints. Mallinckrodt plans to share the data at an upcoming medical meeting.

MS is a chronic, degenerative disease that can cause numerous impairments, including fatigue, balance/coordination issues, numbness or tingling, vision problems, muscle spasms, tremors and emotional changes, and some people with MS experience relapses while on standard therapies¹.

Acthar Gel is U.S. Food and Drug Administration (FDA)-approved for the treatment of acute exacerbations of MS in adults. Controlled clinical trials have shown Acthar Gel to be effective in speeding the resolution of acute exacerbations of MS. However, there is no evidence that it affects the ultimate outcome or natural history of the disease. Please see Important Safety Information for Acthar Gel below.

The registry was designed to assess the characteristics of patients receiving Acthar Gel for MS exacerbations (sometimes referred to as "flares" or "relapses"), as well as the outcome at two months and whether or not the outcome was maintained at six months. The average age of patients was 47 years, and the mean duration of MS was 10 years at the start of the study. Registry data showed that patients treated with Acthar Gel reported significant improvements in symptoms associated with MS exacerbations at two months from baseline, as measured by the MS Impact Scale, version 1 (MSIS 29v1), the primary measure of the study. The response was sustained at six months. Physicians also reported an improvement in physical symptoms in patients treated with Acthar Gel, based on Expanded Disability Status Scale (EDSS) scores.

"Mallinckrodt is committed to generating data that helps clarify to the prescriber those patients appropriate for treatment with Acthar Gel to manage MS relapses," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. "The registry evaluated the effect of Acthar Gel in prospectively defined patients who were treated with Acthar Gel following an acute relapse. In addition, we look forward to Mallinckrodt's ongoing, randomized, double-blind, placebo-controlled OPTIONS study, which we anticipate will provide data on some of the more difficult-to-treat MS patients in the future."

About the Observational Registry of Acthar Gel for Multiple Sclerosis Relapse

• The Observational Registry of Acthar Gel for Multiple Sclerosis Relapse followed patients with recurrent MS relapse for up to 24 months, and a minimum of six months, to characterize the patient population with recurrent MS exacerbations (relapse) and describe MS exacerbation recovery, treatment patterns and safety outcomes in adult patients treated with Acthar Gel in standard practice in the United States.
• The registry enrolled 148 adult (≥18 years) patients at 55 U.S. sites.
• The average age of enrolled patients was 47 years.
• 60 percent of patients reported a history of insufficient treatment response to, intolerance of, or intravenous access problems with high-dose corticosteroid therapy.
• 58 percent reported one or more MS relapses in the two years before enrolling in the registry.
• The primary measure of the registry was MS relapse at month two versus baseline as measured by MSIS-29v1 – physical subscale.
• Adverse events were consistent with those in previous trials of Acthar Gel.
• An electronic patient-reported outcome scale was used to describe MS exacerbation recovery (e.g., neurological functional and symptom improvement; productivity loss) and treatment response over a period of six months following index exacerbation and any relapses, as well as to describe the safety profile of Acthar Gel. Patient assessments were used to describe relapse characteristics
  (e.g., symptoms, time to relapse and relapse treatment) for patients who experienced relapses following the index exacerbation during the study period.
• Acute exacerbations were determined by the treating clinician.

The MSIS-29v1 is a scientifically rigorous, disease-specific, health-related, quality of life instrument that measures the patient's perspective on disease impact. It consists of two subscales assessing the physical and psychological impacts of MS.² 

The EDSS is a clinician-administered assessment scale that measures neurological impairment. It is used to describe and monitor disease progression and is widely used to measure disease outcomes in clinical trials.³ 

A limitation of the study is that, as it was a registry, there was no control group. 

The study and analysis were conducted by Mallinckrodt. Additional information about the study can be found here.

About Multiple Sclerosis
MS is a neurologic disorder that affects the central nervous system (i.e., the brain and spinal cord).⁴ Symptoms can include fatigue, balance/coordination issues, numbness or tingling, vision problems, muscle spasms, tremors and emotional changes. More than eight in 10 people with MS will experience a relapse, or flare-up, that brings new or worsening symptoms.¹

Acthar Gel (repository corticotropin injection) Indications
Acthar Gel is an injectable drug approved by the FDA for the treatment of 19 indications. Of these, today the majority of Acthar use is in these indications:

• Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy)
• The treatment of symptomatic sarcoidosis
• Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age
• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
• The treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar Gel 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
• Inducing a diuresis or a remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus
• Treatment during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis)
• 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

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-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, and 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.

ABOUT MALLINCKRODT
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company's Specialty Brands reportable segment's 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. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. 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.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release includes forward-looking statements concerning Acthar Gel including expectations regarding related clinical trials, its potential impact on patients and anticipated benefits associated with its use. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; and other risks identified and described in more detail in the "Risk Factors" section of Mallinckrodt's most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

CONTACTS
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Mallinckrodt, the "M" brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2019 Mallinckrodt. US-1901601 9/19

References

¹ National Multiple Sclerosis Society. Relapsing-remitting MS (RRMS). Available at: http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS. Accessed September 10, 2019.
² Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The multiple sclerosis impact scale (MSIS-29) -- A new patient-based outcome measure. Brain 2001, 124: 962–973.
³ Kurtzke J: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983, 33: 1444–1452.
⁴ Willis, BMJ Best Practice Multiple Sclerosis. October 2018. p. 4.

SOURCE Mallinckrodt plc

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