First Patient Enrolled in Mallinckrodt Phase 4 Trial of Acthar® Gel (Repository Corticotropin Injection) for Severe Keratitis

STAINES-UPON-THAMES, United Kingdom, Dec. 16, 2019 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a global biopharmaceutical company, today confirmed enrollment of the first patient in the company's Phase 4, multi-center, multiple-dose, open-label study to assess the effects of Acthar Gel as a therapy option in patients with severe keratitis¹.

"In my experience, a considerable number of severe keratitis patients can have persistent disease that may not be resolved by first-line treatment," said Eugene McLaurin, MD and Fellow, American Academy of Ophthalmology and American College of Surgeons. "I am pleased that the first patient has been enrolled in this important Phase 4 study, the results of which may potentially provide data to further support Acthar Gel as a treatment option in appropriate keratitis patients."

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 the product's 19 indications. Please see Important Safety Information below.

"The enrollment of the first patient in this study is an important milestone in our assessment of Acthar's efficacy as a treatment option for patients with keratitis," said Tunde Otulana, M.D., Chief Medical Officer at Mallinckrodt. "We believe this exploratory evaluation of patients whose severe keratitis persists – after the use of 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 "A Multicenter, Open-Label Study to Assess the Efficacy and Safety of Acthar Gel in Subjects with Severe Keratitis." 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 keratitis who meet entry criteria will be treated with Acthar Gel 1 mL (80 units [U]) subcutaneously (SC) two times per week for 12 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 weeks¹.

Response will be evaluated by determining the proportion of patients who improved on the Impact of Dry Eye on Everyday Life scale (time frame: from baseline to 12 weeks) and the proportion of subjects who show improvement from baseline in the IDEEL symptom bother score at 12 weeks¹. 

Full study details can be found on clinicaltrials.gov.

About Severe Keratitis
Keratitis is a painful inflammation of the cornea which can result in partial or total loss of vision if left untreated and is a significant cause of ocular morbidity around the world.² It can result from infectious agents (e.g., microbes including bacteria, fungi, amebae, and viruses) or from noninfectious causes (e.g., eye trauma, chemical exposure, and ultraviolet exposure).³ Conditions that affect the integrity of the ocular surface epithelium (exposure keratitis, neurotrophic keratitis, keratomalacia, recurrent corneal erosions) may also lead to development of sterile corneal ulcers.⁴ Non-infectious corneal ulcers may be associated with various collagen vascular or other autoimmune diseases, sometimes as the presenting sign of the disease.³

About 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)
• 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)
• 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 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 with regard to the study described in this release, as well as 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

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

Media
Daniel Yunger
Kekst CNC
212-521-4879
mallinckrodt@kekstcnc.com

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-1902249 12/19

References

¹ https://clinicaltrials.gov/ct2/show/NCT04169061?term=acthar&recrs=ab&cond=Keratitis&cntry=US&draw=2&rank=1

² Sharma S. Keratitis. Bioscience Reports. 2001;21:419-444.

³ Collier SA, Gronostaj MP, MacGurn, AK, Cope JR, Awsumb KL, Yoder JS, et al. Estimated burden of keratitis--United States, 2010. MMWR Morb Mortal Wkly Rep. 2014;63(45):1027–1030..

⁴ Donzis PB, Mondino BJ. Management of noninfectious corneal ulcers. Surv Ophthalmol. 1987;32:94–110.

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SOURCE Mallinckrodt plc