Mallinckrodt Announces Interim Analysis Results for Therakos® Platform Phase 3 Clinical Trial in Treatment of Pediatric Patients with Steroid Refractory Acute Graft-versus-Host Disease

BEDMINSTER, N.J., Feb. 20, 2019 /PRNewswire/ -- Mallinckrodt Pharmaceuticals (NYSE:MNK), a leading global specialty pharmaceutical company, today announced interim analysis results of its company-sponsored, Phase 3, single-arm, open-label, multi-center study assessing the efficacy of treating steroid-refractory, acute Graft-versus-Host Disease (aGvHD) pediatric patients with UVADEX^® (methoxsalen) Sterile Solution in conjunction with the THERAKOS^® CELLEX^® Photopheresis system. Given the overall response rate exceeded the specified target at the study midpoint, the company is electing not to proceed with further enrollment of additional patients in the clinical trial.

UVADEX solution is U.S. Food and Drug Administration (FDA)-approved for extracorporeal administration with the THERAKOS UVAR XTS^® or 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.

The planned interim analysis occurred at the midway point of enrollment (n=25) when pediatric patients (ages 1-21 years) reached four weeks of therapy to assess response rates. The analysis found an overall response rate of 74%. The company also performed an ad hoc 12-week analysis showing an overall response rate of 48%. The study protocol allows for discontinuation of the study if the treatment overall response rate at the four-week interim analysis is at least 48%. Eleven serious adverse events were reported, leading to two subject withdrawals and two deaths; none were considered related to the UVADEX photopheresis therapy. The safety and effectiveness of THERAKOS CELLEX Photopheresis System for use in treating pediatric patients with steroid-refractory aGvHD has not been evaluated by the FDA or any international regulatory body.

"Mallinckrodt is pleased to have been able to partner with the pediatric transplant community concerning this fragile patient population," said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer, Mallinckrodt. "We believe the full details from the study's interim analysis – which will be made public – will make a meaningful contribution to the body of data related to this critical condition."

More details on the study (NCT02524847) can be found here on www.clinicaltrials.gov.

About Therakos Immunotherapy
Therakos immunotherapy is delivered through CELLEX systems to harness the power of the patient's immune system to treat the skin manifestations of CTCL, and is used by academic medical centers, hospitals, and treatment centers in more than 25 countries. Therakos photopheresis systems are fully integrated closed systems and FDA-approved for the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other forms of treatment.

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. Women of childbearing potential should be advised to avoid becoming pregnant. It is not known whether this drug is excreted in human milk
• 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
• Patients should be advised to avoid all exposure to sunlight during the 24 hours following
• photopheresis treatment
• 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
• Safety in children has not been established
• Thromboembolic events, such as pulmonary embolism and deep vein thrombosis, have been reported with UVADEX administration through photopheresis systems for treatment of patients with graft-versus-host disease, a disease for which UVADEX is not approved.

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%)

For the THERAKOS^® UVAR XTS^®/CELLEX^® 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
• exhibiting idiosyncratic or hypersensitivity reactions to 8-methoxypsoralen/psoralen compounds
• with coagulation disorders
• who have had previous splenectomy

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
• Patients who may not be able to tolerate the fluid changes associated with extracorporeal photopheresis should be monitored carefully
• Procedures, such as renal dialysis, which might cause significant fluid changes (and expose the patient to additional anticoagulation) should not be performed on the same day as extracorporeal photopheresis
• Individual patients may require a heparin dosage that varies from the recommended dose to prevent post-treatment bleeding or clotting during a treatment

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 Full Prescribing Information, including the BOXED WARNING for UVADEX, and see the appropriate THERAKOS Photopheresis System Operator's Manual.

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 Therakos including expectations with regard to the study described in this release. 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
Vice President, Investor Relations and IRO
314-654-3638
[email protected]

Media
Daniel Yunger
Kekst CNC
212-521-4879
[email protected]

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-1900187 02/19 

SOURCE Mallinckrodt Pharmaceuticals

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