Medical Drug Criteria (MDC) Medical Drug Criteria (MDC)
Policy Num: P1.002.022
Policy Name: Rethymic (Allogeneic processed thymus tissue - agdc)
Policy ID: [P1.002.022][Ac L M+ P+ ]
Last Review: September 22, 2025
Next Review: September 20, 2026
| Popultation Reference No. | Populations |
|---|---|
| 1 | Individuals:
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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.
The implantation of allogeneic processed thymus tissue–agdc (Rethymic) meets the definition of medically necessary for immune reconstitution in pediatric patients with congenital athymia.
The implantation of allogeneic processed thymus tissue–agdc (Rethymic) meets the definition of medical necessity when ALL of the following criteria are met (“1” to “8”):
1. The individual has a confirmed diagnosis of congenital athymia AND the diagnosis of severe combined immunodeficiency (SCID) has been ruled out (i.e., no SCID-causing genetic defects identified) - laboratory and/or medical record documentation of the flow cytometry and genetic testing results confirming the diagnosis must be submitted. Flow cytometry must show fewer than 50 naïve T cells/mm3 (CD45RA+, CD62L+) in the peripheral blood or less than 5% of total T cells being naïve in phenotype.
2. Individual's congenital athymia diagnosis has been confirmed by and the individual’s treatment plan (including Rethymic implantation) and follow-up care will be under the supervision of a pediatric immunologist or other specialist with expertise in the management of congenital athymia.
3. The individual is currently receiving, and will continue to receive, standard of care supportive measures for congenital athymia until immune reconstitution is deemed sufficient (generally at least 9 to 12 months after Rethymic treatment) which should include the following (“a”, “b”, and “c”) - medical record documentation of the standard of care supportive measures implemented must be submitted: a. Antimicrobial prophylaxis to prevent bacterial, fungal, and viral infections [at a minimum, this must include Pneumocystis jiroveci pneumonia (PJP) prophylaxis, usually with trimethoprimsulfamethoxazole (TMP-SMX)] b. Immunoglobulin replacement therapy c. Strict infection control, sanitation, and isolation protocols to limit exposure to infectious pathogens.
4. To decrease the risk of graft-versus-host disease (GVHD), the individual will receive immunosuppressive therapy, if needed, prior to and/or after Rethymic treatment based on their disease phenotype (i.e., typical vs. atypical complete DiGeorge syndrome) and pretreatment phytohemagglutinin (PHA) response in accordance with the recommendations in the Rethymic product labeling (Tables 2 and 3). Immunosuppressive therapies most often include anti-thymocyte globulin [rabbit] (Thymoglobulin), methylprednisolone, and cyclosporine.
5. The individual has been, or will be, screened for anti-HLA antibodies prior to receiving Rethymic
6. Implantation of Rethymic will be done by a qualified surgical team in a single surgical session at a qualified hospital
7. The individual has not previously received thymus tissue implantation for the treatment of congenital athymia in their lifetime
8. The Rethymic implantation will not exceed a single, one-time dose (up to 22,000 mm2 of Rethymic surface area per m2 recipient BSA, not to exceed 42 slices) as calculated and supplied by the manufacturer.
Approval duration: 3 months (to allow a single implantation of Rethymic)
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 slice is defined as the contents on a single filter membrane; the 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 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
• Infection Control and Immunoprophylaxis: Immune reconstitution sufficient to protect from infection is unlikely to develop prior to 6 to 12 months after treatment with RETHYMIC. Given the immunocompromised condition of athymic patients, infection control measures should be followed until the development of thymic function can be established as measured through flow cytometry. This should include counseling patients and their caregivers on good handwashing practices and minimizing exposure to visitors. 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 all of the following criteria are met:
o No longer on immunosuppression (at least 10% of CD3+ T cells are naïve in phenotype).
o At least 9 months post-treatment.
o Phytohemagglutinin (PHA) response within normal limits.
o Normal serum IgA is also desirable but not required.
► Two months after stopping immunoglobulin replacement therapy, the IgG trough level should be checked.
o If the IgG trough level is in the normal range for age, the patient can remain off of immunoglobulin replacement.
o If the IgG trough level is lower than the normal range for age, immunoglobulin replacement therapy should be restarted and continued for a year before being retested using the above guidelines.
► Prior to and after treatment with Rethymic, patients should be maintained on Pneumocystis jiroveci pneumonia prophylaxis until all of the following criteria are met:
o No longer on immunosuppression (at least 10% of CD3+ T cells are naïve in phenotype).
o At least 9 months post-treatment. o PHA response within normal limits.
o CD4+ T cell count > 200 cells/mm3.
• Graft versus Host Disease: Monitor and treat patients at risk for the development of graft versus host disease (GVHD). In clinical studies, GVHD occurred in 11 (10%) treated patients of whom 6 (55%) died. Rethymic may cause or exacerbate pre-existing GVHD.
• Autoimmune Disorders: Monitor for the development of autoimmune disorders, including 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: Pre-existing cytomegalovirus infection may result in death prior to the development of thymic function.
• Malignancy: Monitor for the development of lymphoproliferative disorder (blood cancer).
• Transmission of infectious diseases may occur because RETHYMIC is derived from human tissue.
• Vaccine Administration: Immunizations should not be administered in patients who have received RETHYMIC until immune-function criteria have been met.
• Patients should be tested for anti-HLA antibodies prior to treatment.
RETHYMIC is not indicated for the treatment of patients with severe combined immunodeficiency (SCID).
BlueCard/National Account Issues
State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration-approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.
Based on benefits or contract language, Allogeneic Processed Thymus Tissue–agdc (Rethymic®) may be considered either a pharmacy or a medical benefit.
Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.
No drug interaction studies have been conducted with RETHYMIC. If possible, prolonged use of immunosuppressive therapies, including high-dose corticosteroids, should be avoided.
The efficacy and safety of RETHYMIC have been established in pediatric patients with congenital athymia. The efficacy of RETHYMIC has been established in 95 pediatric patients (median age 9 months [range: 33 days to 3 years], including 65 patients age <1 year, 24 patients age 1 to <2 years, and 6 patients age 2 to <3 years at time of treatment) who were treated with RETHYMIC and included in the analysis of efficacy [see Clinical Studies (14)]. The safety of RETHYMIC has been established in 105 pediatric patients (median age 9 months [range: 33 days to 16.9 years] at time of treatment) with congenital athymia who were evaluated for safety following RETHYMIC administration. The safety population included 65 patients age <1 year, 27 patients age 1 to <2 years, 9 patients age 2 to <3 years, 1 patient age 3 to <6 years, and 3 patients age 13 to 17 years at time of treatment. Within the safety population, survival was similar across age groups. Adverse reactions were reported at similar frequencies across the age groups and were generally of similar types and severities.
No Interqual Criteria Applicable.
There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.
| Codes | Number | Description |
|---|---|---|
| HCPCS | J3590 | Unclassified biologics |
| ICD-10-CM | D81.9 | Combined immunodeficiency, unspecified |
| D82.1 | Di George’s syndrome | |
| D82.9 | Immunodeficiency associated with major defect, unspecified | |
| Q89.8 | Other specified congenital malformations | |
| Q89.9 | Congenital malformation, unspecified |
| Date | Action | Description |
|---|---|---|
| 9/22/ 2025 | MDC CREATED | New MDC. Medical Drug Criteria approved at the September 2025 Pharmacy Criteria Meetting. |