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Mallinckrodt Presents Interim Findings of Multiple Sclerosis Relapse Registry for H.P. Acthar® Gel

-- Data  Presented at Annual Meeting of Consortium of Multiple Sclerosis Centers --

STAINES-UPON-THAMES,  United Kingdom – June 1, 2018 – Mallinckrodt plc (NYSE: MNK), a leading  global specialty pharmaceutical company, today presented interim data from the  company-sponsored Observational Registry of H.P. Acthar® Gel (repository  corticotropin injection) for Multiple Sclerosis (MS) Relapse patients at the 2018  Annual Meeting of the Consortium of Multiple Sclerosis Centers, held in  Nashville, Tenn.

The  presentation was entitled “A Prospective Observational Registry of Repository  Corticotropin Injection for the Treatment of Multiple Sclerosis Relapse:  Baseline Characteristics and Interim Results1.” The poster can be accessed here.

Tunde Otulana, M.D.,  Chief Medical Officer at Mallinckrodt, said, “Despite recent advances in the  treatment of MS, many patients still experience relapses and may only achieve  an incomplete recovery following treatment. Over time, this may lead to an  accrual of disability2,3,4. Mallinckrodt is  committed to conducting studies in MS relapse patients treated with Acthar to  collect valuable real-world data about their treatment patterns, MS relapse  recovery and safety outcomes. We look forward to also learning more from data  generated in Mallinckrodt’s ongoing Phase 4 pilot study to assess Acthar  response and safety in patients with relapsing MS whose flares are not  responding to initial high-dose corticosteroid therapy.”

H.P.  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 H.P.  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

Study  Details and Key Findings

A Prospective Observational Registry of  H.P. Acthar Gel for the Treatment of Multiple Sclerosis Relapse is enrolling patients  and collecting demographic data to characterize the patient population who  receive H.P. Acthar Gel to treat acute MS relapse. The study will describe  treatment patterns, MS relapse recovery and safety outcomes. The goal is to  enroll 160 patients at up to 54 sites over 36 months, with a target follow-up  duration of up to 24 months. The primary endpoint in this study is the evaluation  of the efficacy of the drug based on physical subscale of the MS Impact scale,  version 1 (MSIS-29v1).  The MSIS-29v1 is  a well-validated, patient-rated outcome scale that measures the impact of MS on  day-to-day life. Patients who have experienced a relapse are treated with H.P.  Acthar Gel and are evaluated with the MSIS-29v1 at baseline, two months and six  months following MS relapse. Further details on the study can be found on  clinicaltrials.gov here.

Preliminary  data on 80 patients (enrolled as of August 30, 2017 – intention-to-treat n = 62)  found:

     
  • Patients are predominantly female (90%),  Caucasian (85.5%) and, on average, approximately 48 years old with baseline mean Expanded Disability Status Scale5 of 4.2 and mean MSIS-29v1 physical subscale  score of 55.8 following index relapse;
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  • In this  interim analysis of the observational study, compared to baseline, H.P. Acthar Gel showed =8  points improvement on the MSIS-29v1 physical subscale of 40% and 55% of  patients at 2 months and 6 months, respectively, following MS relapse. 
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  • At least 73%  of patients are receiving a disease-modifying therapy at time of relapse;
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  • Median number  of doses of H.P. Acthar Gel received is five, with median dose strength of 80 U;
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  • Age and higher  MSIS-29v1 physical subscore at time of relapse have shown to be predictors of  poor patient response to corticosteroid therapy6, highlighting need for additional treatment options;
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  • Patients were considerably older in current study (mean age 48) than most  previous reports on relapse recovery (mean ages in mid-30s); therefore, this study population  may be expected to experience greater rates of treatment resistance than  previous studies7,8,9; and
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  • A total of 42 adverse events (AEs) were reported,  most commonly nausea (n=2), urinary tract infection (n=2), headache (n=2), and rash  (n=2); nine serious AEs were experienced by eight  patients, most commonly MS exacerbation (n=5) and weakness (n=2), with only one  leading to discontinuation of Acthar. 

 

Limitations

The  current study is a prospective observational registry that collects real world  data that describes how H.P. Acthar Gel is being used in clinical practice.  Therefore, the study does not specify the dosing regimens that are employed by  investigators or the use of various concomitant disease modifying treatments.  The heterogeneity of these variables in the study population may result in increased  variability in the results when compared to studies that control for these  variables. The current study measures improvement of patients compared to their  baseline measures, but as an observational study does not utilize placebo or  active control groups as comparators.   Hence, some of the improvement observed in the current study could be  due to factors other than treatment with H.P. Acthar Gel.

ABOUT  MULTIPLE SCLEROSIS
  MS is a neurologic disorder that affects the  central nervous system (i.e., the brain and spinal cord).10 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.11

About H.P. Acthar Gel (repository corticotropin  injection)
  Indications
  H.P. 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:

     
  • Treatment during an  exacerbation or as maintenance therapy in selected cases of systemic lupus  erythematosus
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  • Monotherapy for the  treatment of infantile spasms in infants and children under 2 years of age
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  • The treatment of acute  exacerbations of multiple sclerosis in adults. Controlled clinical trials have  shown H.P. 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
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  • Inducing a diuresis or a  remission of proteinuria in nephrotic syndrome without uremia of the idiopathic  type or that due to lupus erythematosus
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  • Treatment during an  exacerbation or as maintenance therapy in selected cases of systemic  dermatomyositis (polymyositis)
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  • The treatment of  symptomatic sarcoidosis
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  • 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)
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  • 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
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  • Administration of live or  live attenuated vaccines is contraindicated in patients receiving  immunosuppressive doses of Acthar
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  • Acthar is contraindicated  where congenital infections are suspected in infants
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  • 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
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  • Acthar may increase  susceptibility to new infection or reactivation of latent infections
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  • 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
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  • Cushing’s syndrome may  occur during therapy but generally resolves after therapy is stopped. Monitor  patients for signs and symptoms
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  • Acthar can cause  elevation of blood pressure, salt and water retention, and hypokalemia. Blood  pressure, sodium and potassium levels may need to be monitored
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  • Acthar often acts by  masking symptoms of other diseases/disorders. Monitor patients carefully during  and for a period following discontinuation of therapy
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  • 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
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  • 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
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  • Patients with comorbid  disease may have that disease worsened. Caution should be used when prescribing  Acthar in patients with diabetes and myasthenia gravis
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  • Prolonged use of Acthar  may produce cataracts, glaucoma and secondary ocular infections. Monitor for  signs and symptoms
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  • 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
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  • There is an enhanced  effect in patients with hypothyroidism and in those with cirrhosis of the liver
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  • Long-term use may have  negative effects on growth and physical development in children. Monitor  pediatric patients
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  • Decrease in bone density  may occur. Bone density should be monitored for patients on long-term therapy
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  • 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
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  • 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 parents and  caregivers of IS patients, please also see Medication Guide.

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. 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 H.P. Acthar Gel including  expectations with regard to the study described in this release, as well as  future research plans and potential impact on patients. 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

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

Mallinckrodt, the "M" brandmark and  the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company.  Other brands are trademarks of a Mallinckrodt company or their respective  owners. © 2018 05/18

 

   

1 Due BR, Becker PM, Coyle PK. A  prospective observational registry of repository corticotropin injection for  the treatment of multiple sclerosis relapse: baseline characteristics and  interim results. 2018 Annual Meeting of the Consortium of Multiple Sclerosis Centers.

   

2 Goodin DS, Reder AT, Bermel RA, et al. Relapses in  multiple sclerosis: relationship to disability. Mult Scler Relat Disord. 2016;  6:10-20.

   

3 Kalincik T. Multiple sclerosis relapses:  epidemiology, outcomes and management. A systematic review. Neuroepidemiology.  2015; 44(4):199-214.

   

4 Lublin FD, Baier M, Cutter G. Effect of relapses on  development of residual deficit in multiple sclerosis. Neurology. 2003;  61(11):1528-1532.

   

5 The Expanded Disability Status Scale (EDSS) is a  method of quantifying disability in multiple sclerosis and monitoring changes  in the level of disability over time. It is widely used in clinical trials and  in the assessment of people with MS. Available at : https://www.mstrust.org.uk/a-z/expanded-disability-status-scale-edss. Accessed May 18, 2018.

   

6 Rakusa M, Cano SJ, Porter B, et al. A predictive  model for corticosteroid response in individual patients with MS relapses. PLoS  One. 2015; 10(3):e0120829.

   

7 Le Page E, Veillard D, Laplaud DA, et al. Oral  versus intravenous high-dose methylprednisolone for treatment of relapses in  patients with multiple sclerosis (COPOUSEP): a randomised, controlled,  double-blind, non-inferiority trial. Lancet. 2015; 386(9997):974-981.

   

8 Martinelli V, Rocca MA, Annovazzi P, et al. A  short-term randomized MRI study of high-dose oral vs intravenous  methylprednisolone in MS. Neurology. 2009; 73(22):1842-1848.

   

9 Thompson AJ, Kennard C, Swash M, et al. Relative  efficacy of intravenous methylprednisolone and ACTH in the treatment of acute  relapse in MS. Neurology. 1989; 39(7):969-971.

   

10 Multiple Sclerosis Foundation. Get Educated-Common  Questions-Multiple Sclerosis. Available  at: https://msfocus.org/Get-Educated/Common-Questions#What is Multiple  Sclerosis. Accessed May 18, 2018.

   

11 National Multiple Sclerosis Society.  Relapsing-remitting MS (RRMS). Available at: http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS.  Accessed May 18, 2018.