Mallinckrodt Celebrates 30th Anniversary of THERAKOS® Photopheresis Therapy

STAINES-UPON-THAMES, England, May 3, 2017 /PRNewswire/ -- Mallinckrodt plc (NYSE: MNK), a leading global specialty pharmaceutical company, marked the 30^th anniversary of THERAKOS^® Photopheresis at the 2017 Annual Meeting of the American Society for Apheresis (ASFA), May 3-6, in Fort Lauderdale, Fla.

The innovative THERAKOS Photopheresis System was the first to deliver extracorporeal photopheresis (ECP) for the palliative treatment of the skin manifestations of Cutaneous T-cell Lymphoma (CTCL) that is unresponsive to other forms of treatment. CTCL is a rare form of non-Hodgkin's lymphoma that is estimated to affect up to 20,000 people across the U.S.¹

"Therakos transformed the field of apheresis 30 years ago with its pioneering ECP technology. Today, THERAKOS Photopheresis remains a mainstay of treatment for the skin manifestations of CTCL for patients who are no longer responsive to skin-directed therapies," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer of Mallinckrodt. "This is a significant milestone for those who understand firsthand the tremendous contribution the technology has made."

THERAKOS Photopheresis is a cell-based immunomodulatory therapy that involves withdrawal of blood that is then centrifuged to separate the white blood cells from the red blood cells and plasma. The red blood cells and plasma are immediately returned to the patient. The white blood cells are treated with a photosensitizing agent (UVADEX^® (methoxsalen) Sterile Solution) and activated by ultraviolet light, which is believed to initiate a reaction from the body's immune system.^2,3 The treated white blood cells are then promptly reinfused into the patient. While the exact mechanism of action is not known, the treated white blood cells undergo apoptosis, which is believed to trigger an immune response against CTCL cells.⁴

THERAKOS Photopheresis was approved by the U.S. Food and Drug Administration (FDA) in 1987 for the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other forms of treatment.⁴ Since then, physicians in other countries globally have used the technology across different immune-modulated conditions. Marketing authorizations vary by country.

"Extracorporeal photopheresis has stood the test of time," said Ellen J. Kim, M.D., Associate Professor in Dermatology at Perelman School of Medicine at the University of Pennsylvania and Medical Advisory Council Chair, Cutaneous Lymphoma Foundation (CTL). "It was among the earliest U.S. FDA-approved immunotherapies and remains an important option in the treatment of patients who experience skin manifestations of CTCL."

Mallinckrodt diversified its Specialty Brands portfolio with the acquisition of THERAKOS Photopheresis in 2015, expanding its footprint in hospitals worldwide. The CELLEX^® System, the latest-generation photopheresis platform, includes advanced procedural features and automation that significantly reduced treatment administration time for many patients. Mallinckrodt is the world's only provider of integrated ECP delivery systems, which are used by academic medical centers, hospitals and treatment centers in more than 25 countries.

ABOUT CUTANEOUS T-CELL LYMPHOMA
Cutaneous T-cell lymphoma is a rare type of non-Hodgkin's lymphoma in which certain white blood cells called T-lymphocytes become cancerous and affect the skin.¹ Because CTCL can look like common skin diseases such as psoriasis, eczema, and dermatitis, it may take an average of five to six years before it is diagnosed.⁵ CTCL causes visible skin symptoms and manifestations that can be severe and debilitating such as extensive redness, peeling, burning, soreness, itchiness all over the body, and different types of rashes.⁶ In addition to skin manifestations of CTCL, some patients develop extensive tumors, and experience blood, lymph node and/or internal organ involvement with serious complications.¹ Onset of this rare condition is often noted to occur between the ages of 40 and 60 years old¹, and men are twice as likely to develop the condition.⁷  

About UVADEX (methoxsalen) Sterile Solution

INDICATIONS AND USAGE
UVADEX^® (methoxsalen) Sterile Solution is indicated for extracorporeal administration with the THERAKOS^® UVAR XTS^® or THERAKOS CELLEX^® Photopheresis System in the palliative treatment of the skin manifestations of Cutaneous T-Cell Lymphoma (CTCL) that is unresponsive to other forms of treatment.

IMPORTANT SAFETY INFORMATION
CAUTION: READ THE THERAKOS UVAR XTS or THERAKOS CELLEX PHOTOPHERESIS SYSTEMS' OPERATOR'S MANUAL PRIOR TO PRESCRIBING OR DISPENSING THIS MEDICATION.

CONTRAINDICATIONS

UVADEX is contraindicated in patients exhibiting idiosyncratic or hypersensitivity reactions to methoxsalen, other psoralen compounds or any of the excipients. Patients possessing a specific history of a light sensitive disease state should not initiate methoxsalen therapy.

Diseases associated with photosensitivity include lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism.

UVADEX is contraindicated in patients with aphakia, because of the significantly increased risk of retinal damage due to the absence of lenses. Patients should not receive UVADEX if they have any contraindications to the photopheresis procedure.

WARNINGS AND PRECAUTIONS

• Patients who are receiving concomitant therapy (either topically or systemically) with known photosensitizing agents such as anthralin, coal tar or coal tar derivatives, griseofulvin, phenothiazines, nalidixic acid, halogenated salicylanilides (bacteriostatic soaps), sulfonamides, tetracyclines, thiazides, and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal and methyl orange may be at greater risk for photosensitivity reactions with UVADEX.
• Oral administration of methoxsalen followed by cutaneous UVA exposure (PUVA therapy) is carcinogenic. Methoxsalen also causes DNA damage, interstrand cross-links and errors in DNA repair.
• Methoxsalen may cause fetal harm when given to a pregnant woman. There are no adequate and well-controlled studies of methoxsalen in pregnant women. If UVADEX is used during pregnancy, or if the patient becomes pregnant while receiving UVADEX, the patient should be apprised of the potential hazard to the fetus.
• After methoxsalen administration, exposure to sunlight and/or ultraviolet radiation may result in "premature aging" of the skin.
• Since oral psoralens may increase the risk of skin cancers, monitor closely those patients who exhibit multiple basal cell carcinomas or who have a history of basal cell carcinomas.
• Serious burns from either UVA or sunlight (even through window glass) can result if the recommended dosage of methoxsalen is exceeded or precautions are not followed.
• Exposure to large doses of UVA light causes cataracts in animals. Oral methoxsalen exacerbates this toxicity. Serum methoxsalen concentrations are substantially lower after extracorporeal UVADEX treatment than after oral methoxsalen treatment. Nevertheless, if the lens is exposed to UVA light while methoxsalen is present, photoactivation of the drug may cause adducts to bind to biomolecules within the lens. Instruct patients emphatically to wear UVA absorbing, wrap-around sunglasses for 24 hours after UVADEX treatment.

ADVERSE REACTIONS

• Side effects of photopheresis (UVADEX used with the THERAKOS Photopheresis System) were primarily related to hypotension secondary to changes in extracorporeal volume (>1%).

USE IN SPECIFIC POPULATIONS

• Pregnancy Category D. (See WARNINGS AND PRECAUTIONS)
• Breastfeeding: It is not known whether this drug is excreted in human milk.
• Pediatric Use: Safety in children has not been established.
• Renal impairment: Although renal transplant recipients with poor renal function have been treated with photopheresis using UVADEX, little additional information is available on the use of UVADEX in patients with varying degree of renal impairment.
• Hepatic impairment: No specific information is available on the use of photopheresis with UVADEX in patients with hepatic impairment.

For the THERAKOS^® Photopheresis Procedure:

INDICATIONS

The THERAKOS UVAR XTS^® Photopheresis System/THERAKOS CELLEX^® Photopheresis System is indicated for use in the ultraviolet-A (UVA) irradiation, in the presence of the photoactive drug 8-methoxypsoralen (8-MOP^®), of extracorporeally circulating leukocyte-enriched blood, in the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma (CTCL), in persons who have not been responsive to other forms of treatment.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

The THERAKOS UVAR XTS or THERAKOS CELLEX Photopheresis Systems are not designated, sold or intended for use except as indicated. Certain underlying medical conditions contraindicate THERAKOS Photopheresis, including patients who cannot tolerate extracorporeal volume loss during the leukocyte-enrichment phase, patients exhibiting idiosyncratic or hypersensitivity reactions to 8-methoxypsoralen/psoralen compounds, and patients with coagulation disorders.

WARNINGS AND PRECAUTIONS

THERAKOS Photopheresis treatments should always be performed in locations where standard medical emergency equipment is available. Volume replacement fluids and/or volume expanders should be readily available throughout the procedure.

ADVERSE REACTIONS

• Hypotension may occur during any treatment involving extracorporeal circulation. Closely monitor the patient during the entire treatment for hypotension.
• Transient pyretic reactions, 37.7-38.9°C (100-102°F), have been observed in some patients within six to eight hours of reinfusion of the photoactivated leukocyte-enriched blood. A temporary increase in erythroderma may accompany the pyretic reaction.
• Treatment frequency exceeding labeling recommendations may result in anemia.
• Venous access carries a small risk of infection and pain.

Please see accompanying Full Prescribing Information, including the Boxed Warning for UVADEX and refer to the appropriate THERAKOS Photopheresis System Operator's Manual for more 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; and analgesics and hemostasis products. The company's core strengths include the acquisition and management of highly regulated raw materials and specialized chemistry, formulation and manufacturing capabilities. The company's Specialty Brands segment includes branded medicines and its Specialty Generics segment includes specialty generic drugs, active pharmaceutical ingredients and external manufacturing. 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 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.

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

Meredith Fischer
Chief Public Affairs Officer
314-654-3318
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Investor Relations
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Senior Vice President, Investor Strategy and IRO
314-654-6649
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Daniel J. Speciale, CPA
Director, Investor Relations
314-654-3638
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References

¹ Cutaneous T-Cell Lymphomas. National Organization for Rare Disorders, Available at: https://rarediseases.org/rare-diseases/cutaneous-t-cell-lymphomas/ Accessed March 6, 2017.
² Marshall SR. Technology insight: ECP for the treatment of GvHD–can we offer selective immune control without generalized immunosuppression? Nat Clin Pract Oncol 2006;3:302–14. Cited in PubMed; PMID 16757968.
³ Alfred, A., et. al., The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society. Br J Haematol. doi:10.1111/bjh.14537
⁴ UVADEX® (methoxsalen) Sterile Solution [package insert]. West Chester, PA: Therakos, Inc.; 2014
⁵ Mishra A, Porcu P. Blood. 2011; 118: 5717–5718.
⁶ About CTCL. Mallinckrodt Website. Available at: http://www.therakos.com/about-ctcl Accessed March 29, 2017
⁷ Cutaneous T-Cell Lymphoma Facts. Leukemia and Lymphoma Society. Available at: https://www.lls.org/sites/default/files/file_assets/cutaneoustcelllymphoma.pdf

SOURCE Mallinckrodt plc

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