Currently Enrolling Trials
Rethymic (Allogeneic processed thymus tissue–agdc) is composed of human allogeneic (donor-derived) thymus tissue that is processed and cultured, and then implanted into patients to help reconstitute immunity (improve immune function) in patients who are athymic. Congenital athymia is a rare immune disorder in which a child is born without a thymus.
Rethymic is specifically indicated for immune reconstitution in pediatric patients with congenital athymia.
Rethymic is administered by a surgical procedure. The dosage is determined by the total surface area of the Rethymic slices and recipient body surface area (BSA). A Rethymic slice is defined as the contents on a single filter membrane; the Rethymic slices are variable in size and shape. The recommended dose range is 5,000 to 22,000 mm2 of Rethymic surface area/m2 recipient BSA. The manufacturer calculates the dose in advance for the specific patient; the amount of product provided is adjusted at the manufacturing facility to ensure the maximum dose for the patient cannot be exceeded. Up to 42 cultured Rethymic slices will be provided for each patient. At the time of surgery, the manufacturing personnel communicate to the surgical team the portion of the product that represents the minimum dose. Patients with evidence of maternal engraftment or an elevated response to phytohemagglutinin (PHA) should receive Rethymic with immunosuppressive medications.
Mechanism of Action
Rethymic is intended to reconstitute immunity in patients who are athymic. The proposed mechanism of action involves the migration of recipient T cell progenitors from the bone marrow to the implanted Rethymic slices, where they develop into naïve immunocompetent recipient T cells. Evidence of thymic function can be observed with the development of naïve T cells in the peripheral blood; this is unlikely to be observed prior to 6-12 months after treatment with Rethymic.
Adverse effects associated with the use of Rethymic may include, but are not limited to, the following:
- hypertension (high blood pressure)
- cytokine release syndrome
- hypomagnesemia (low magnesium)
- renal impairment / failure (decrease of kidney function)
- thrombocytopenia (low platelets)
- graft versus host disease
Clinical Trial Results
FDA approval was based on ten prospective single-arm, open-label studies with patient enrollment from 1993 to 2020 form the basis of the RETHYMIC data set. One hundred and five patients were surgically implanted with RETHYMIC under one of 10 Institutional Review Board (IRB)-approved protocols. Ninety-five patients were included in the Efficacy Analysis Set (EAS) and 105 patients were included in the Safety Analysis Set. Survival rates were analyzed with the longest follow-up period of 25.5 years. In the EAS, Kaplan-Meier estimated survival rates were 77% at oneyear and 76% at two years. For patients who were alive at one year post implantation, the Kaplan-Meier estimated long-term survival rate was 94% at a median follow-up time of 10.7 years. For the patients in the clinical trials, naïve T-cell levels were measured using flow cytometry atsix, 12, and 24 months after implantation with RETHYMIC. Patients in the clinical trials started out with very few naïve T cells but naïve CD4+and CD8+T cells began to reconstitute over the first year, with a durable increase through year two. Reductions in the number of infections over time during the first two years after treatment were statistically significant.