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;
- 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.
- At least 73% of patients are receiving a disease-modifying therapy at time of relapse;
- Median number of doses of H.P. Acthar Gel received is five, with median dose strength of 80 U;
- 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;
- 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
- 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.
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)
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
- Monotherapy for the treatment of infantile spasms in infants and children under 2 years of age
- 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
- 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)
- The treatment of symptomatic sarcoidosis
- 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)
- 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
- 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
- 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
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.
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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.
Daniel J. Speciale, CPA
Investor Relations and Strategy Officer
Senior Communications Manager
Chief Public Affairs Officer
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.
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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.
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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.