How is RETHYMIC made?

Unlike a transplant, RETHYMIC is developed for one child at a time through a complex process using donor thymus tissue1,2

Donation of thymus tissue

When an infant ≤9 months of age undergoes cardiac surgery, some thymus tissue may need to be removed to access the heart. With consent of the infant donor’s parents or guardian, the thymus tissue is donated and undergoes extensive testing to determine the viability and safety of the tissue for making RETHYMIC.2

Unlike many other medications or specialty biologics, RETHYMIC is not an off-the-shelf product. The thymus tissue from a single infant donor allows for the manufacturing of RETHYMIC for one patient.1

Development of RETHYMIC

The time the engineering process takes depends on multiple factors and can be completed between 12 and 21 days.3

RETHYMIC is engineered in a dedicated environment that follows strict FDA requirements. The manufacturing personnel have been extensively trained on proper safety protocols to maintain a sterile environment and avoid cross contamination.

The engineering process requires manufacturing personnel to manually change the media, preserving thymic epithelial cells and tissue structure while depleting most of the donor thymocytes. During this time, the donor thymus tissue goes through multiple rigorous tests—some of which are repeated—to ensure the product meets FDA safety standards.1,3

Implantation of RETHYMIC

The dosage is determined based on the total surface area of the RETHYMIC tissue slices, and the amount implanted is calculated based on the recipient’s body surface area.1

Once released from the manufacturing facility, RETHYMIC must be implanted within a limited time frame at the treatment center.3

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RETHYMIC is a one-time treatment administered via a single surgical procedure.1,4

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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

Indication

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).

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Sumitomo Pharma is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO is a registered trademark of Sumitomo Chemical Co., Ltd., used under license. Sumitomo Pharma America, Inc. is a U.S. subsidiary of Sumitomo Pharma Co. Ltd. ENZYVANT CONNECT®, RETHYMIC®, and their logos are registered trademarks of Enzyvant Therapeutics GmbH. © 2023 Enzyvant Therapeutics GmbH. All rights reserved. US—2300143 11/2023