How is RETHYMIC made?

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.¹

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.²

Illustration of a microscope

Manufacturing 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.^2,3

Illustration of implanted RETHYMIC

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.²

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

RETHYMIC is a one-time treatment administered via a single surgical procedure.^2,4

Learn about the implantation

See what you should expect after your patients receive treatment with RETHYMIC.

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RETHYMIC Connect™ provides support and resources for patients with congenital athymia and their caregivers.

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Indication and Important Safety Information

Important Safety Information

Infection Control and Immunoprophylaxis: Immune reconstitution sufficient to protect from infection is unlikely to develop prior to 6-12 months after treatment with RETHYMIC. Follow infection control measures until the development of thymic function is established as measured by flow cytometry. Closely monitor patients for signs of infection. If fever develops, assess the patient via lab results and treat as clinically indicated. Patients should be maintained on immunoglobulin replacement therapy (IgG) and Pneumocystis jirovecii pneumonia prophylaxis until specified criteria are met. IgG trough level should be checked 2 months after stopping IgG to determine whether the patient may remain off IgG.

Graft versus Host Disease (GVHD): RETHYMIC may cause or exacerbate pre-existing GVHD, for which patients should be closely monitored and treated. Risk factors include atypical complete DiGeorge anomaly phenotype, prior hematopoietic cell transplantation (HCT), and maternal engraftment. Patients with specified elevated baseline T cell proliferative response to PHA should receive immunosuppressants to decrease this risk. GVHD may manifest as fever, rash, lymphadenopathy, elevated bilirubin and liver enzymes, enteritis, and/or diarrhea.

Autoimmune Disorders: 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 complete blood counts with differential, liver enzymes, serum creatinine, urinalysis, and thyroid function.

Renal Impairment: Pre-existing renal impairment is a risk factor for death.

Cytomegalovirus Infection (CMV): In the clinical studies, 4 out of 4 patients with pre-existing CMV infection died.

Malignancy: Due to underlying immune deficiency, patients who receive RETHYMIC may be at risk of developing post-treatment lymphoproliferative disorder. Patients should be tested for Epstein-Barr virus and CMV prior to and 3 months after treatment or after any suspected exposure.

Transmission of Serious Infections and Transmissible Infectious Diseases: Transmission of infectious disease may occur because RETHYMIC is derived from human tissue, and product manufacturing includes porcine- and bovine-derived reagents.

Vaccine Administration: Immunizations should not be given in patients treated with RETHYMIC until immune-function criteria have been met. Live virus vaccines should not be given until patients have met the criteria for and received inactivated vaccines.

Anti-HLA Antibodies: All patients should be screened for anti-HLA antibodies prior to receiving RETHYMIC. Patients testing positive should receive RETHYMIC from a donor who does not express those HLA alleles.

HLA Typing: HLA matching is required in patients who have received a prior HCT or a solid organ transplant. Patients who have received a HCT are at increased risk of developing GVHD after RETHYMIC if the HCT donor does not fully match with RETHYMIC.

Deaths: Of the 105 patients in clinical studies, 29 patients died, including 23 deaths in the first year (<365 days) after implantation.

Adverse Reactions: The most common (>10%) adverse events included hypertension, cytokine release syndrome, rash, hypomagnesemia, renal impairment/failure, thrombocytopenia, and GVHD.

Indication

RETHYMIC® 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. Sumitomo Pharma America, Inc. Enzyvant receives FDA approval for RETHYMIC® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. Accessed June 27, 2024. https://www.us.sumitomo-pharma.com/newsroom/press-releases/Enzyvant-Receives-FDA-Approval-for-RETHYMIC-allogeneic-processed-thymus-tissue-agdc-a-One-Time-Regenerative-Tissue-Based-Therapy-for-Pediatric/ 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.

References: 1. Collins C, Sharpe E, Silber A, Kulke S, Hsieh EWY. Congenital athymia: genetic etiologies, clinical manifestations, diagnosis, and treatment. J Clin Immunol. 2021;41(5):881-895. doi:10.1007/s10875-021-01059-7 2. Markert ML, Gupton SE, McCarthy EA. Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol. 2022;149(2):747-757. doi:10.1016/j.jaci.2021.06.028 3. Immune Deficiency Foundation. Patient & Family Handbook for Primary Immunodeficiency Diseases. 6th ed. 2019. 4. Hsieh EWY, Kim-Chang JJ, Kulke S, Silber A, O’Hara M, Collins C. Defining the clinical, emotional, social, and financial burden of congenital athymia. Adv Ther. 2021;38(8):4271-4288. doi:10.1007/s12325-021-01820-9 5. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 6. Sumitomo Pharma America, Inc. Enzyvant receives FDA approval for RETHYMIC® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. Accessed June 27, 2024. https://www.us.sumitomo-pharma.com/newsroom/press-releases/Enzyvant-Receives-FDA-Approval-for-RETHYMIC-allogeneic-processed-thymus-tissue-agdc-a-One-Time-Regenerative-Tissue-Based-Therapy-for-Pediatric/

References: 1. Collins C, Sharpe E, Silber A, Kulke S, Hsieh EWY. Congenital athymia: genetic etiologies, clinical manifestations, diagnosis, and treatment. J Clin Immunol. 2021;41(5):881-895. doi:10.1007/s10875-021-01059-7 2. Markert ML, Gupton SE, McCarthy EA. Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol. 2022;149(2):747-757. doi:10.1016/j.jaci.2021.06.028 3. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 4. Sumitomo Pharma America, Inc. Enzyvant receives FDA approval for RETHYMIC® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. Accessed June 27, 2024. https://www.us.sumitomo-pharma.com/newsroom/press-releases/Enzyvant-Receives-FDA-Approval-for-RETHYMIC-allogeneic-processed-thymus-tissue-agdc-a-One-Time-Regenerative-Tissue-Based-Therapy-for-Pediatric/

References: 1. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 2. Sumitomo Pharma America, Inc. Enzyvant receives FDA approval for RETHYMIC® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. Accessed June 27, 2024. https://www.us.sumitomo-pharma.com/newsroom/press-releases/Enzyvant-Receives-FDA-Approval-for-RETHYMIC-allogeneic-processed-thymus-tissue-agdc-a-One-Time-Regenerative-Tissue-Based-Therapy-for-Pediatric/ 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.

References: 1. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 2. Markert ML, Gupton SE, McCarthy EA. Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol. 2022;149(2):747-757. doi:10.1016/j.jaci.2021.06.028 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.

References: 1. 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. 2. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 3. Food and Drug Administration. Summary Basis for Regulatory Action. October 8, 2021. BLA STN: 125685/0 4. Sumitomo Pharma America, Inc. Enzyvant receives FDA approval for RETHYMIC® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. Accessed June 27, 2024. https://www.us.sumitomo-pharma.com/newsroom/press-releases/Enzyvant-Receives-FDA-Approval-for-RETHYMIC-allogeneic-processed-thymus-tissue-agdc-a-One-Time-Regenerative-Tissue-Based-Therapy-for-Pediatric/

References: 1. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 2. Sumitomo Pharma America, Inc. Enzyvant receives FDA approval for RETHYMIC® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. Accessed June 27, 2024. https://www.us.sumitomo-pharma.com/newsroom/press-releases/Enzyvant-Receives-FDA-Approval-for-RETHYMIC-allogeneic-processed-thymus-tissue-agdc-a-One-Time-Regenerative-Tissue-Based-Therapy-for-Pediatric/

References: 1. Hsieh EWY, Kim-Chang JJ, Kulke S, Silber A, O’Hara M, Collins C. Defining the clinical, emotional, social, and financial burden of congenital athymia. Adv Ther. 2021;38(8):4271-4288. doi:10.1007/s12325-021-01820-9 2. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023.

References: 1. RETHYMIC [package insert]. Marlborough, MA: Sumitomo Pharma America, Inc; 2023. 2. 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 3. Gupton SE, McCarthy EA, Markert ML. Care of children with DiGeorge before and after cultured thymus tissue implantation. J Clin Immunol. 2021;41(5):896-905. doi:10.1007/s10875-021-01044-0