Discover the wonder of childhood
What is RETHYMIC?
RETHYMIC is a first-of-its-kind, FDA-approved tissue-based treatment for patients with congenital athymia.1,2
RETHYMIC is a one-time treatment that is engineered to help patients with congenital athymia develop an immune system sufficient to fight infections.1,2
RETHYMIC is not indicated for the treatment of patients with severe combined immunodeficiency.1
Unlike a transplant, RETHYMIC is engineered donor thymus tissue manufactured during a 12- to 21-day process. RETHYMIC is implanted in the thigh muscle via a single surgical procedure.1
Brynlee, a patient with congenital athymia.
How RETHYMIC works
The proposed mechanism of action involves the migration of the patient’s T-cell progenitors to RETHYMIC where they develop into T cells that are sufficient to fight infections.1
Evidence of thymic function may be observed with this development in the peripheral blood. However, immune reconstitution sufficient to protect against infection is unlikely to develop prior to 6 to 12 months after treatment with RETHYMIC.1
The efficacy and safety of RETHYMIC were studied across 10 clinical trials.1
Unlike a transplant, RETHYMIC is engineered for one patient at a time through a complex process using donor thymus tissue.1,3
Enzyvant CONNECT provides support and resources for patients with congenital athymia and their caregivers.
Indication and Important Safety Information
Important Safety Information
Immune reconstitution sufficient to protect from infection is unlikely to develop prior to 6-12 months after treatment with RETHYMIC. Given the immunocompromised condition of athymic patients, follow infection control measures until the development of thymic function is established as measured through flow cytometry. Monitor patients closely for signs of infection including fever. If a fever develops, assess the patient by blood and other cultures and treat with antimicrobials as clinically indicated. Patients should be maintained on immunoglobulin replacement therapy until specified criteria are met, and two months after stopping, IgG trough level should be checked. Prior to and after treatment with RETHYMIC, patients should be maintained on Pneumocystis jiroveci pneumonia prophylaxis until specified criteria are met.
RETHYMIC may cause or exacerbate pre-existing graft versus host disease (GVHD). Monitor and treat patients at risk for the development of GVHD. Risk factors for GVHD include atypical complete DiGeorge anomaly phenotype, prior hematopoietic cell transplantation (HCT) and maternal engraftment. GVHD may manifest as fever, rash, lymphadenopathy, elevated bilirubin and liver enzymes, enteritis, and/or diarrhea.
Autoimmune-related adverse events occurred in patients treated with RETHYMIC. These events included: thrombocytopenia, neutropenia, proteinuria, hemolytic anemia, alopecia, hypothyroidism, autoimmune hepatitis, autoimmune arthritis, transverse myelitis, albinism, hyperthyroidism, and ovarian failure. Monitor for the development of autoimmune disorders, including complete blood counts with differential, liver enzymes, serum creatinine, urinalysis, and thyroid function.
Pre-existing renal impairment is a risk factor for death.
In the clinical studies of RETHYMIC, 4 out of 4 patients with pre-existing cytomegalovirus infection died. The benefits/risks of treatment should be considered prior to treating patients with pre-existing CMV infection.
Because of the underlying immune deficiency, patients who receive RETHYMIC may be at risk of developing post-treatment lymphoproliferative disorder. Patients should be monitored for the development of lymphoproliferative disorder.
Transmission of infectious disease may occur because RETHYMIC is derived from human tissue and because product manufacturing includes porcine- and bovine-derived reagents.
Immunizations should not be administered in patients who have received RETHYMIC until immune-function criteria have been met.
All patients should be screened for anti-HLA antibodies prior to receiving RETHYMIC. Patients testing positive for anti-HLA antibodies should receive RETHYMIC from a donor who does not express those HLA alleles. HLA matching is required in patients who have received a prior HCT or a solid organ transplant. Patients who have received a prior HCT are at increased risk of developing GVHD after RETHYMIC if the HCT donor did not fully match the recipient.
Of the 105 patients in clinical studies, 29 patients died, including 23 deaths in the first year (< 365 days) after implantation.
The most common (>10%) adverse events related to RETHYMIC included: hypertension, cytokine release syndrome, rash, hypomagnesemia, renal impairment/failure, thrombocytopenia, and graft versus host disease.
To report suspected adverse reactions, please contact the FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch
RETHYMIC® (allogeneic processed thymus tissue–agdc) is indicated for immune reconstitution in pediatric patients with congenital athymia.
Limitations of Use:
RETHYMIC is not indicated for the treatment of patients with severe combined immunodeficiency (SCID).
References: 1. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 2. Enzyvant Therapeutics GmbH. Enzyvant receives FDA approval for RETHYMIC® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. Enzyvant Therapeutics, Inc. October 8, 2021. Accessed March 3, 2023. https://enzyvant.com/enzyvant-receives-fda-approval-for-rethymic-allogeneic-processed-thymus-tissue-agdc-a-one-time-regenerative-tissue-based-therapy-for-pediatric-congenital-athymia/ 3. Markert ML, McCarthy EA, Gupton SE, Lim AP. Cultured thymus tissue transplantation. In: Sullivan KE, Stiehm ER, eds. Stiehm’s Immune Deficiencies: Inborn Errors of Immunity. 2nd ed. Elsevier; 2020:1229-1239.