Data Published on Acthar® Gel (repository corticotropin injection) Disease Status and Utilization Patterns in Uveitis Patients in Journal of Ocular Pharmacology and Therapeutics

STAINES-UPON-THAMES, United Kingdom, April 9, 2019 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, today announced data from a retrospective chart review that analyzed physician assessments of 91 U.S. patients diagnosed with uveitis who had been treated with Acthar^® Gel (repository corticotropin injection) in the previous 12 months. All patients had completed or were still receiving treatment at the time of the review. In response to a survey question, physicians reported that 84 percent of patients who completed or were still in treatment with Acthar Gel had improvement in disease status overall, and 86 percent had improvements in vision. Uveitis is a leading cause of preventable blindness in adults. Results of the study were recently published online ahead of print in the Journal of Ocular Pharmacology and Therapeutics. Please see Important Safety Information for Acthar Gel below.

Acthar Gel is U.S. Food and Drug Administration (FDA)-approved 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 and anterior segment inflammation.

"This is one of the first and largest studies of its kind to look at real-world medication patterns in the treatment of uveitis – for which data are greatly limited – and demonstrates our commitment to support informed and appropriate decision-making for patients," said Tunde Otulana, M.D., Senior Vice President and Chief Medical Officer at Mallinckrodt. "We are committed to examining treatments and clinical practices for patients with uveitis that can lead to improvements in their disease management. Real-world data can provide additional evidence of the potential utility of available therapeutic options for patients."

Study Details¹

• The study was a retrospective medical record review of physicians' assessments of 91 patients diagnosed with uveitis, most of whom had moderate to severe visual impairment, who were treated with Acthar Gel. Average time since diagnosis was four years.
• Patients were selected from among a nationally representative sample of 21 ophthalmologists who were randomly selected for recruitment from a database of Acthar Gel prescribers and from the American Medical Association Physician Masterfile (a national database of physicians). Data were abstracted from patient medical records using an electronic data collection instrument and were collected between September and October 2017.
• Signs and symptoms noted at baseline included blurred vision, light sensitivity, floaters, loss of visual acuity, eye pain, and eye redness. Disease severity was most often moderate.
• All patients were taking other medications for uveitis before initiation of Acthar Gel. These included steroid eye drops, oral steroids, intraocular steroid injections, nonsteroidal eye drops and biologics.
• All patients had received treatment with Acthar Gel in the past 12 months and had either completed a course of Acthar Gel or were receiving Acthar Gel treatment at the time of data collection.
• There were 17 different initial dosing regimens documented in the study; however, most patients (n=70, 77 percent) were prescribed an initial regimen of 40–80 units, administered subcutaneously once or twice weekly. According to the Acthar Gel prescribing information, usual dosing of Acthar Gel is 40–80 units via subcutaneous or intramuscular injection every 1-3 days.²

Highlights of the Assessments

• Based on notes in medical records, physicians reported that overall disease status had improved in 84 percent (n=76) of patients after therapy with Acthar Gel. They also reported:
• 86 percent (n=78) had improvements in vision.
• 27 percent (n=25) had improvements in eye pain.
• 26 percent (n=24) had improvements in vitreous haze.
• 24 percent (n=22) had reduction of background medication use.
• 23 percent (n=21) had improvements in vitreous flare.
• 18 percent (n=16) had improvements in macular edema.

Additional Observations

• Of the patients treated with Acthar Gel, the number who were taking concomitant uveitis medications was reduced over time.
• At the start of treatment with Acthar Gel, 100 percent (n=91) of patients were on concomitant uveitis medication.
• During treatment with Acthar Gel, the number of patients on concomitant uveitis treatment decreased to 57 percent (n=52).
• Three months after initiation of Acthar Gel therapy, 22 percent (n=20) of patients remained on concomitant uveitis therapy. Among these patients, many were able to reduce their dose of concomitant uveitis medications.

Study Limitations

• The study was a retrospective collection of data from medical records, which may be incomplete.
• Outcomes may be influenced by therapies not documented in the patient medical records.
• The study's scope did not include quantification of patients' outcomes, such as diagnostic measurements or safety endpoints.
• Physician assessments of patient outcomes may be subjective.
• Most patients were on multiple therapies so clinical outcomes may not be solely attributable to Acthar Gel.

The study was conducted by Mallinckrodt.

"These data add to the body of knowledge on uveitis, a leading cause of preventable blindness in adults in the U.S., and enhance understanding of treatment options for uveitis," said Robert C. Wang, M.D., Partner, Texas Retina Associates, Dallas Texas, Clinical Associate Professor, UTSW Dallas Texas. "Studies designed to assess medication utilization and practice patterns are greatly needed to guide appropriate treatment decisions for uveitis patients."

About Uveitis
Uveitis is a complex mix of acute or chronic inflammatory eye disorders that affects the uveal tract (a layer of tissue just behind the outer layer of the eye) and adjacent structures, including the sclera, cornea, vitreous humor, retina, and optic nerve head.^3,4,5,6 Symptoms vary based on the site of inflammation, but can include decreased vision, eye pain, tearing, redness, light sensitivity, and floaters.^3,4 Uveitis has numerous etiologies, associated conditions, and underlying immune responses that complicate its diagnosis and treatment.^4,7 Uveitis accounts for five percent to 20 percent of cases of legal blindness in the United States. In the United States, the annual incidence (occurrence of new cases) of uveitis ranges between 24.9 and 52.4 per 100,000 persons.^8,9,10  It mostly affects individuals of working age.⁴

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 reporting 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; and analgesics. Its Specialty Generics and Amitiza reporting segment includes specialty generic drugs, active pharmaceutical ingredients and AMITIZA^® (lubiprostone). 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 regarding 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
For Trade Media Inquiries
Caren Begun
Green Room Communications
201-396-8551
[email protected]

For Financial/Dailies Media Inquiries
Daniel Yunger
Kekst CNC
212-521-4879
[email protected]

Investor Relations
Daniel J. Speciale, CPA
Vice President, Investor Relations and IRO
314-654-3638
[email protected]

References

¹ Nelson WW, Lima AF, Kranyak J, et al. Retrospective medical record review to describe use of repository corticotropin injection among patients with uveitis in the United States [published online ahead of print January 24, 2019]. J Ocul Pharmacol Ther. doi: 10.1089/ jop.2018.0090.
² Acthar® Gel (repository corticotropin injection) (prescribing information). Mallinckrodt ARD, Inc.
³ Barisani-Asenbauer T, Maca SM, Mejdoubi L, Emminger W, Machold K, Auer H. Uveitis—a rare disease often associated with systemic diseases and infections—a systematic review of 2619 patients. Orphanet J Rare Dis. 2012;7:57.
⁴ Mustafa M, Muthusamy P, Hussain SS, Shimmi SC, Sein MM. Uveitis: pathogenesis, clinical presentations and treatment. IOSR J Pharm. 2014;4:42-47.
⁵ Guly CM, Forrester JV. Investigation and management of uveitis. BMJ. 2010;341:c4976.
⁶ Chan CC, Li Q. Immunopathology of uveitis. Br J Ophthalmol. 1998;82:91-99.
⁷ Lee 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.
⁸ Acharya, NR, Tham VM, Esterberg E, et al. Incidence and prevalence of uveitis: results from the Pacific Ocular Inflammation Study. JAMA Ophthalmol. 2013;131:1405-1412.
⁹ Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111:491-500; discussion 500.
¹⁰ Suhler EB, Lloyd MJ, Choi D, Rosenbaum JT, Austin DF Incidence and prevalence of uveitis in Veterans Affairs Medical Centers of the Pacific Northwest. Am. J. Ophthalmol. 2008;146:890.e8–896.e8.

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-1900407 4/19

SOURCE Mallinckrodt plc

Related Links

http://www.mallinckrodt.com