First Patient Screened in Mallinckrodt Phase 4 Trial of H.P. Acthar® Gel (Repository Corticotropin Injection) for Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

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Oct 26, 2018, 06:45 ET

STAINES-UPON-THAMES, United Kingdom, Oct. 26, 2018 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, today confirmed screening of the first patient in the company's Phase 4, multi-center, multiple-dose, open label study to assess the effects of H.P. Acthar Gel as a therapy option in patients with Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU).

H.P. Acthar Gel is approved by the U.S. Food and Drug Administration (FDA) for the 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 – one of 19 indications.

"I am pleased that the first patient has been screened in this important Phase 4 study, the results of which may potentially provide further evidence to support Acthar as a treatment option in appropriate uveitis patients." said C. Stephen Foster, M.D., Founder and President, Massachusetts Eye Research and Surgery Institution, Professor of Ophthalmology, Harvard Medical School, Founder of the Ocular Immunology and Uveitis Foundation, Waltham, Mass. "In my experience, a considerable number of uveitis patients can have persistent disease that may not be resolved by first-line treatment."

"The screening of the first patient in this study is an important milestone in enhancing our understanding of Acthar's effectiveness and potential utility as a treatment option for certain uveitis patients," said Tunde Otulana, M.D., Chief Medical Officer at Mallinckrodt. "We believe this exploratory evaluation of patients with severe uveitis – despite being on one or more standard treatments – can potentially help physicians better understand which individuals may benefit from the drug as a treatment alternative."

About the Trial
The Phase 4 clinical study is titled "Efficacy and Safety of H.P. Acthar Gel in Subjects With Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU)." This is a Phase 4, multicenter, multiple dose, open label study to examine the effects of Acthar in adult subjects, with a target enrollment of 30. Subjects with current severe NIPPU who meet entry criteria will be treated with H.P. Acthar Gel 1 mL (80 units [U]) subcutaneously (SC) two times per week for 36 weeks. Initial treatment will be followed by a taper to Acthar 1 mL (80 U) SC once a week for two weeks, then 0.5 mL (40 U) SC once a week for two weeks. All subjects will have a follow-up contact 28 (± 14) days after their last dose of study drug.

Response will be evaluated by vitreous haze (time frame: from baseline to 36 weeks) for the proportion of subjects with a two-step or more reduction from baseline (or achievement of Grade 0) in vitreous haze at 36 weeks. Full study details can be found on clinicaltrials.gov.

Vitreous haze is the obscuration of fundus details by vitreous cells and protein exudation. It impacts vision more profoundly than anterior inflammation and therefore is used commonly as an outcome measure for clinical trials involving intermediate, posterior, or panuveitis.¹

About Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU)
Uveitis impacts a variety of patients each year². A complex mix of acute or chronic allergic and inflammatory disorders, uveitis can affect the anterior, intermediate, and posterior structures of the eye as well as the uveal tract^3,4. Uveitis accounts for 5%-20% of legal blindness cases in the United States. The annual incidence of uveitis is estimated to be 17-52/100,000 persons per year. The annual prevalence of uveitis is estimated to be 38-714/100,000 persons². Adults of working age are most commonly affected by this condition⁴. Uveitis is a disease with a number of causes, associated conditions, and underlying immune responses that complicate its diagnosis and treatment.^4,5

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:

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)
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 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
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 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
[email protected]

Media
Rhonda Sciarra
Senior Communications Manager
908-238-6765
[email protected]

Meredith Fischer
Chief Public Affairs Officer
908-997-9294
[email protected]

¹Davis JL, Madow B, Cornett J, et al. Scale for photographic grading of vitreous haze in uveitis. Am J Ophthalmol. 2010;150(5):637-641.e1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220938/. Accessed Oct. 7, 2018.
²Miserocchi E, Fogliato G, Modorati G, et al. Review on the worldwide epidemiology of uveitis. Eur J Ophthalmol. 2013;23(5):705-717. doi:10.5301/ejo.5000278.
³Chan CC, Li Q. Immunopathology of uveitis. Br J Ophthalmol. 1998;82:91-9
⁴Guly CM, Forrester JV. Investigation and management of uveitis. BMJ. 2010;341:821-826. doi:10.1136/bmj.c4976.
⁵Lee RWJ, Dick AD. Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation. Eye. 2012;26(1):17-28. doi:10.1038/eye.2011.255.

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