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Uvadex
Uvadex (methoxsalen) was approved for the following therapeutic use:
Uvadex (methoxsalen) is indicated for extracorporeal administration with the Therakos Cellex Photopheresis System for the treatment of steroid-refractory and steroid-intolerant chronic graft versus host disease (cGVHD) in adults following allogeneic HSC transplantation.
Methoxsalen is a naturally occurring photoactive substance found in the seeds of the Ammi majus (Umbelliferae) plant. It belongs to a group of compounds known as psoralens or furocoumarins. Uvadex is used in combination with the Therakos Cellex Photopheresis System to extracorporeally treat leukocyte enriched buffy coat. Although extracorporeal photopheresis (ECP) with methoxsalen has been used clinically for many years, knowledge regarding the full mechanism underlying ECP has not been fully elucidated. It is generally accepted that the molecular processes which lead to apoptotic cell death involve the intercalating of methoxsalen into the double-stranded DNA molecule within the nucleus. On activation by exposure to UVA light, methoxsalen binds to the pyrimidine bases of the nucleic acid (thymine, cytosine and uracil) and forms covalent cross-links between the two DNA strands. The formation of these photoadducts results in the proliferative arrest and death of lymphocytes. In addition, studies have demonstrated that photopheresis may result in the induction of an autoregulatory host response which recognizes and specifically suppresses photo-treated effector T-cell populations.
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Uvadex was considered favourable for the therapeutic use approved.