RETHYMIC (Allogeneic processed thymus tissue – agdc)

Allogeneic processed thymus tissue–agdc (Rethymic) was approved by the US Food and Drug Administration (FDA) in October 2021 for immune reconstitution in pediatric patients with congenital athymia. It is the first treatment to be approved for this fatal condition. The thymus tissue is obtained from donors less than or equal to 9 months of age undergoing cardiac surgery. The manufacturing process preserves the thymic epithelial cells and tissue structure and depletes most of the donor thymocytes from the tissue. The proposed mechanism of action involves the migration of recipient T cell progenitors from the bone marrow to the implanted thymus tissue, where they develop into naïve immunocompetent recipient T cells. Evidence of thymic function will be observed by the development of naïve T cells in the peripheral blood occurring at least 6 months after treatment. Congenital athymia is an ultra-rare condition in which children are born without a thymus, causing vulnerability to life-threatening infections and immune dysregulation. The estimated incidence of congenital athymia in the US is approximately 17 to 24 infants per 4 million live births annually. The thymus is responsible for the development of mature T cells and is the only organ where thymocytes can mature, be selected, and survive to become naive T cells. T cells originate in the bone marrow as progenitor cells; however, the bone marrow does not contain the specialized tissue required for T-cell maturation. Without a functioning thymus, the inability to produce immunocompetent T cells leads to immunodeficiency manifested as increased susceptibility to infection. With only supportive care, children with congenital athymia typically do not survive beyond 2 to 3 years of age. Congenital athymia is often associated with other conditions, such as DiGeorge syndrome (a.k.a., 22q11.2 deletion syndrome); mutations in the genes TBX1, CHD7 (CHARGE syndrome – coloboma, heart defects, choanal atresia, growth or mental retardation, genital hypoplasia, and ear anomalies and/or deafness), and FOXN1 (FOXN1 deficiency); and diabetic embryopathy. These systemic conditions make the complex treatment of congenital athymia even more complicated. Early detection of congenital athymia is critical, as the sooner it is identified, the sooner isolation, infection prevention measures, and prophylactic antimicrobials can be initiated. Newborn screening plays a crucial role in early detection. <a id="