Brand Name
Rethymic
Generic Name
Thymocyte-Depleted
View Brand Information FDA approval date: October 08, 2021
Form: Implant
What is Rethymic (Thymocyte-Depleted)?
RETHYMIC ® is indicated for immune reconstitution in pediatric patients with congenital athymia. 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 . Limitations of Use RETHYMIC is not indicated for the treatment of patients with severe combined immunodeficiency .
Approved To Treat
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Related Clinical Trials
Congenital Athymia Patient Registry of RETHYMIC
Summary: This Congenital Athymia Patient Registry is an observational exposure-based registry study. It uses a prospective cohort design to follow patients who have been treated with RETHYMIC. Clinical studies conducted with investigational RETHYMIC showed that treatment can result in immune reconstitution and prolong life. This treatment-based registry is being conducted to learn more about the reconstitu...
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Brand Information
RETHYMIC (allogenic thymocyte-depleted thymus tissue-agdc)
1INDICATIONS AND USAGE
RETHYMIC
2DOSAGE FORMS AND STRENGTHS
RETHYMIC consists of yellow to brown slices of processed thymus tissue with varying thickness and shape. Each drug product dish contains up to 4 RETHYMIC slices that adhere to circular filter membranes on top of surgical sponges in 5 mL of medium. The RETHYMIC slices are variable in size and shape; a RETHYMIC slice is defined as the contents of a single filter membrane. The dosage is based on the total surface area of the RETHYMIC slices, and the amount administered is calculated based on recipient BSA. The surgeon should implant as many RETHYMIC slices as possible within the recommended dose range of 5,000 to 22,000 mm
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The most common adverse reactions (incidence in at least 10% of patients) reported following administration of RETHYMIC were hypertension (high blood pressure), cytokine release syndrome, rash, hypomagnesemia (low magnesium), renal impairment / failure (decrease of kidney function), thrombocytopenia (low platelets), and graft versus host disease.
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data described in this section are derived from 10 prospective, single-center, open-label studies, and include 105 patients who were treated with RETHYMIC in these studies and who had at least one year of follow-up. Table 1 lists the adverse reactions occurring in 105 patients who were treated with RETHYMIC in these studies.
Of the 105 patients, 29 patients died after receiving RETHYMIC, including 23 deaths in the first year (<365 days) after treatment with RETHYMIC. Causes of death in the first year included 13 deaths due to infection or complications due to infection, 5 deaths due to respiratory failure / hypoxia, 3 deaths due to hemorrhage-related events, and 2 deaths due to cardiorespiratory arrest. Of the 6 patients who died more than 1 year after treatment with RETHYMIC, the deaths were considered unrelated to study treatment: 2 died due to respiratory failure and 1 died due to each of the following: cardiopulmonary arrest, intracranial hemorrhage, infection, and unknown cause.
5DRUG INTERACTIONS
No drug interaction studies have been conducted with RETHYMIC. If possible, prolonged use of immunosuppressive therapies, including high-dose corticosteroids, should be avoided.
6OVERDOSAGE
The maximum recommended dose is 22,000 mm
During clinical development one patient received a dose higher (23,755 mm
7DESCRIPTION
RETHYMIC consists of yellow to brown slices of allogeneic processed thymus tissue for administration by surgical implantation. Three to 11 drug product containers, with a total of 10 to 42 RETHYMIC slices, are provided for each patient. Each drug product container provides up to 4 RETHYMIC slices of variable size. The total dose, based on the number of slices administered to the patient, is 5,000 to 22,000 mm
Thymus tissue is obtained from donors less than or equal to 9 months of age undergoing cardiac surgery. This thymus tissue is aseptically processed and cultured for 12 to 21 days to produce RETHYMIC slices. Each product lot is manufactured from a single unrelated donor and one product lot treats a single patient. The manufacturing process preserves the thymic epithelial cells and tissue structure and depletes most of the donor thymocytes from the tissue. These RETHYMIC slices are then surgically implanted into patients with congenital athymia.
The product manufacture uses reagents derived from animal materials. The surgical sponge used during culturing is porcine-derived. Fetal bovine serum is a component in the culture medium used to culture the thymus slices and RETHYMIC is formulated in media that is supplemented with fetal bovine serum. Therefore, bovine- and porcine-derived proteins will be present in RETHYMIC. These animal-derived reagents are tested for animal viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma before use.
8CLINICAL STUDIES
The efficacy of RETHYMIC was evaluated in 10 prospective, single-center, open-label studies that enrolled a total of 105 patients, including 95 patients in the primary efficacy analysis. The demographics and baseline characteristics of the patients enrolled in the clinical studies were similar across studies. Across the efficacy population, 59% were male; 70% were White, 22% were Black, 4% were Asian/Pacific Islander; 2% were American Indian/Alaskan Native; and 2% were multi-race. The median (range) age at the time of treatment was 9 months (1-36). The diagnosis of congenital athymia was based on flow cytometry documenting fewer than 50 naïve T cells/mm
Patients with heart surgery anticipated within 4 weeks prior to, or 3 months after, the planned RETHYMIC treatment date, patients with human immunodeficiency virus (HIV) infection, and patients who were not considered good surgical candidates were excluded from study participation.
Patients in the efficacy population received RETHYMIC in a single surgical procedure at a dose of 4,900 to 24,000 mm
The Kaplan-Meier estimated survival rates were 77% (95% CI [0.670, 0.841]) at 1 year and 76% (95% CI [0.658, 0.832]) at 2 years. For patients who were alive at 1 year after treatment with RETHYMIC, the survival rate was 94% at a median follow-up of 10.7 years.
Without treatment, congenital athymia is fatal in childhood. In a natural history population observed from 1991 through 2017, 49 patients diagnosed with congenital athymia received supportive care only. The 2-year survival rate was 6%, with all patients dying by 3 years of age. This population included 33 (67%) males. The most common cause of death was infection in 26 (53%) patients. Other common causes (≥10%) included support withdrawn in 7 (14%) patients, respiratory arrest in 5 (10%) patients, and cardiac arrest in 5 (10%) patients.
The Kaplan-Meier estimated survival rates for the RETHYMIC clinical trial population and the natural history population are shown in Figure 5. Four patients with >50 naïve T cells/mm
Figure 5: Kaplan-Meier Survival by Year (RETHYMIC Efficacy Analysis Population and Natural History Population)
RETHYMIC significantly reduced the number of infections over time. In the first year after treatment with RETHYMIC, the number of patients with an infection event onset 6 to ≤ 12 months after treatment decreased by 38% (from 63 to 39) relative to the number of patients with an infection event onset in the first 6 months post-treatment. A two-year analysis showed a decrease in both the number of patients with an infection event and the mean number of infection events per patient, with an onset in the first 12 months post-treatment as compared to 12 to ≤ 24 months after treatment. There was a mean difference of 2.9 events (p<0.001) per patient.
Naïve CD4
9PATIENT COUNSELING INFORMATION
Advise patients and/or their caregivers that:
- Immune reconstitution sufficient to protect from infection usually develops between 6-12 months after treatment with RETHYMIC, but for some patients elevated naïve T cell numbers are not observed until 2 years after treatment. Strict infection control measures should be observed until the healthcare provider confirms that immune function has been reconstituted through the evaluation of blood using flow cytometry and the criteria for the discontinuation of immunoglobulin replacement therapy and
- Congenital athymia alters the immune response to vaccines. Instruct patients and/or their caregivers to notify their healthcare professional to evaluate the immune status of RETHYMIC recipients prior to receiving vaccinations
- Immunosuppression should be administered in patients with elevated T cell response, maternal engraftment, or oligoclonal T cell expansion and autoreactive T cells manifested by rash, lymphadenopathy and/or diarrhea. Inform patients and/or their caregivers on risks associated with short-term and long-term use of immunosuppression and refer them to review the risks of the specific immunosuppressants prescribed with their physician.
- Congenital athymia is associated with a wide spectrum of genetic anomalies. Instruct patients and/or their caregiver to consult with a clinical geneticist prior to receiving RETHYMIC.
Advise patients and/or their caregivers of the following risks
- Graft versus Host Disease
- Autoimmune Disorders (patient's immune (defense) system mistakenly attacks patient's body)
- Renal Impairment (decrease of kidney function)
- Cytomegalovirus Infection
- Malignancy (
- Transmission of Serious Infections and Transmissible Infectious Diseases