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DUBLIN, May 3, 2021 /PRNewswire/ -- Mallinckrodt plc (OTCMKTS: MNKKQ), a global biopharmaceutical company, today announced data from its Phase 4, multi-center, open-label study to assess the efficacy and safety of Acthar^® Gel (repository corticotropin injection) in adult patients with treatment-resistant, severe non-infectious keratitis, a disease which involves painful inflammation of the cornea.¹ The full results were presented in a poster at The Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, and further data will be shared at the upcoming virtual International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Annual Meeting. The poster can be accessed here on the company's website.

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.² Please see Important Safety Information for Acthar Gel below.

The primary efficacy endpoint of the study was the proportion of patients who improved by 12 points or more in the symptom bother module of the Impact of Dry Eye on Everyday Life (IDEEL) score at week 12. The IDEEL is a patient-reported outcome assessment with three modules—impact on daily life, treatment satisfaction and symptom bother—and six dimensions. After 12 weeks of treatment with Acthar Gel, 50.0 percent (n=17) of patients experienced improvements in their symptom bother score by at least 12 points, a clinically important change³ (95% CI 33.2, 66.8).⁴

"As ophthalmologists, we rely heavily on patient-reported symptoms when evaluating severe keratitis, especially for those who require alternative treatments," said one of the study authors David Wirta, M.D., Ophthalmologist, Eye Research Foundation, Newport Beach. "The clinically important improvement in the symptom bother module is very encouraging and helps us better understand the potential impact for Acthar Gel to effectively treat appropriate patients with severe keratitis who are in need of additional treatment options."

Exploratory endpoints included the change from baseline to week 12 in each item of the Visual Analog Scale (VAS), and corneal fluorescein staining and conjunctival lissamine green staining as measured by Ora Calibra™ scales. After 12 weeks of treatment with Acthar Gel, all symptoms assessed by the VAS had improved from baseline, with the most pronounced improvements observed for eye dryness and discomfort. Additionally, improvements from baseline in corneal fluorescein staining and conjunctival lissamine green staining were observed as early as week four and were sustained through week 12. Additionally, the proportions of patients who experienced greater than or equal to 20, 30 or 50 percent improvement in the IDEEL symptom bother score at week 12 were 50.0 percent (95% CI 33.2, 66.8), 44.1 percent (95% CI 27.4, 60.8) and 14.7 percent (95% CI 2.8, 26.6), respectively.⁴ 

Safety was assessed regarding treatment-emergent adverse events (TEAEs) and serious TEAEs collected throughout the study. Of patients in the safety population (n=36), 33.3 percent experienced ≥1 TEAE after initiation of Acthar Gel treatment; most TEAEs were single incidences. In the study, the most commonly reported TEAE was hypertension (n=2). No serious TEAEs were related to the study drug.⁴ 

"These data provide meaningful evidence to support Acthar Gel's potential role in improving outcomes for patients with severe keratitis that persists after the use of one or more standard treatments," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. "We are pleased to be able to share these important data broadly with the healthcare community with the hopes of helping physicians better understand which individuals may benefit from the drug as a treatment alternative." 

About the Study⁴:

• The study was designed to evaluate the efficacy and safety of Acthar Gel in adult patients with treatment-resistant, severe non-infectious keratitis.
• In the 16-week study period, 36 patients were enrolled at eight sites across the United States.
• To ensure inclusion of moderate to severe dry eye patients, eligibility criteria included all of the following in at least one eye (the same eye) at screening and baseline:
• Inferior corneal fluorescein staining score of at least two points in any field in at least one eye.
• Sum corneal fluorescein staining score ≥4.
• Sum lissamine green conjunctival score of ≥2.
• Conjunctival redness score ≥1 (0-4 scale).
• Schirmer score ≥1 mm and ≤10 mm/5 min in at least one eye.
• Ocular Discomfort Score of ≥2.
• After a 28-day screening, subjects who met entry criteria were treated with Acthar Gel 1 mL (80 units) subcutaneously twice per week for 12 weeks, followed by a tapering period of four weeks.
• The mean age of the study population was 63.3 years, and most patients were female (71.4 percent), White (80.0 percent) and not of Hispanic or Latino ethnicity (94.3 percent).

Find out more information about the study here on the ClinicalTrials.gov website.

About Severe Keratitis
Keratitis is a painful inflammation of the cornea and is a significant cause of ocular morbidity around the world.¹ 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).⁵ Non-infectious severe keratitis may be associated with various collagen vascular or other autoimmune diseases, sometimes as the presenting sign of the disease.⁶

IMPORTANT SAFETY INFORMATION

Contraindications

Acthar is contraindicated:

• For intravenous administration
• In infants under 2 years of age who have suspected congenital infections
• With concomitant administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of Acthar
• 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 origin

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-adrenal (HPA) axis 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 axis 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. Monitor blood pressure and sodium and potassium levels
• 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 gastrointestinal (GI) bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain GI disorders. Monitor for signs of perforation and bleeding
• Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression to 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 and Acthar activity
• There may be 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 in 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

• Commonly reported postmarketing adverse reactions for Acthar include injection site reaction, asthenic conditions (including fatigue, malaise, asthenia, and lethargy), fluid retention (including peripheral swelling), insomnia, headache, and blood glucose increased
• The most common adverse reactions for the treatment of infantile spasms (IS) are increased risk of infections, convulsions, hypertension, irritability, and pyrexia. Some patients with IS progress to other forms of seizures; IS sometimes masks these seizures, which may 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 additional Important Safety 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 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.

CONTACT

Media Inquiries
Caren Begun
Green Room Communications
201-396-8551
caren@greenroompr.com

Investor Relations
Daniel J. Speciale
Vice President, Finance and Investor Relations Officer
314-654-3638
daniel.speciale@mnk.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. ©2021 Mallinckrodt. US-2001768 04/21

References

¹ Sharma S. Keratitis. Bioscience Reports. 2001;21:419-444.
² Acthar® Gel (repository corticotropin injection) [prescribing information]. Mallinckrodt ARD LLC.
³ Fairchild CJ, et al. Optom Vis Sci. 2008;85(8):699-707.
⁴ Grieco J, McLaurin E, Ousler G, Liu J, Kacmaz O, Wirta D. Results from a multicenter, open-label, Phase 4 study of repository corticotropin injection in patients with treatment-resistant severe non-infectious keratitis. Presented at: Association for Research in Vision and Ophthalmology Annual Meeting; May 1, 2021; San Francisco, CA.
⁵ 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.
⁶ Donzis PB, Mondino BJ. Management of noninfectious corneal ulcers. Surv Ophthalmol. 1987;32:94–110.

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