Identification

Summary

Allogeneic processed thymus tissue is a cell transplant therapy indicated for immune reconstitution in pediatric patients with congenital athymia.

Brand Names
Rethymic
Generic Name
Allogeneic processed thymus tissue
DrugBank Accession Number
DB16736
Background

Allogeneic processed thymus tissue is used for immune reconstitution in immune disorders where the patients are severely immunocompromised due to the absence of a functional thymus, such as congenital athymia. As part of the immune system, the thymus is an organ responsible for the maturation and selection of T cells 3; thus, patients without a functional thymus experience profound immunodeficiency and are placed at higher risk for developing life-threatening or fatal infections and immune dysregulation.5 Congenital athymia is a rare condition that leads to the absence of a thymus at birth and a high premature mortality rate, with patients typically dying by age two or three.5 Multiple factors contribute to the development of congenital athymia, such as genetic abnormalities, congenital syndromes, and environmental factors. Allogeneic processed thymus tissue implantation works by migrating the recipient’s bone marrow-derived stem cells to the implanted cultured thymus tissue that develops immunocompetent naïve T cells.3

On October 8, 2021, FDA approved allogeneic processed thymus tissue-agdc, under the market name RETHYMIC, as a one-time regenerative tissue-based therapy for immune reconstitution in pediatric patients with congenital athymia: this marks the first and only FDA-approved treatment for such therapeutic indication.5

Type
Biotech
Groups
Approved
Biologic Classification
Cell transplant therapies
Other cell transplant therapies
Synonyms
  • Allogeneic processed thymus tissue-agdc
  • Allogeneic thymocyte depleted processed thymus tissue slices
  • Allogeneic thymocyte-depleted thymus tissue-agdc
  • Allogenic thymocyte-depleted thymus tissue-agdc
External IDs
  • RVT-082

Pharmacology

Indication

Allogeneic processed thymus tissue is indicated for immune reconstitution in pediatric patients with congenital athymia. It is not indicated for the treatment of patients with severe combined immunodeficiency (SCID).4

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Allogeneic processed thymus tissue is an engineered human thymus tissue that is used to regenerate the thymic function 5 and reconstitutes immunity in patients who are athymic to develop immunocompetent naïve T cells. The presence of naïve T cells in the peripheral blood of the recipient is evident of thymic function, although this effect is unlikely to be observed prior to 6-12 months following treatment with allogeneic processed thymus tissue.4 In recent studies of thymus transplantation, thymopoiesis in the transplanted thymus was observed within two months of transplantation and naïve T cells in the peripheral blood were detected in about three to five months after transplantation.1 In an immune evaluation study of thymus recipients surviving beyond 1 year, recipients possessed naïve T cells with normal mitogen proliferative responses and diverse T cell receptor repertoires.2

Mechanism of action

The thymus is a critical organ of the immune system as it is responsible for the maturation and selection of thymocytes so that they ultimately become naïve T cells. Normally, T cell precursors from the bone marrow migrate to the thymus for maturation and differentiation. Congenital athymia is characterized by the absence of a thymus at birth, leading to the lack of functional T cells and profound immune deficiency; therefore, patients with congenital athymia are at high risk for developing life-threatening or fatal infections as well as autologous graft-versus-host disease.3

Allogeneic processed thymus tissue aims to restore thymic function in patients with congenital athymia. Thymus tissue is obtained from unrelated infant donors to be processed and cultured, so that the thymus tissue preserves thymic epithelial cells but lacks most of the donor thymocytes. The resulting allogeneic processed thymus tissue is then surgically implanted into the muscles of recipients with congenital athymia. T cell progenitors from the bone marrow of the recipient are migrated to the implanted allogeneic processed thymus tissue,4 which provides an environment for progenitor cells to undergo positive and negative selection to develop into naïve immunocompetent recipient T cells.2,4

Absorption

The pharmacokinetic properties of allogeneic processed thymus tissue are not known.

Volume of distribution

The pharmacokinetic properties of allogeneic processed thymus tissue are not known.

Protein binding

The pharmacokinetic properties of allogeneic processed thymus tissue are not known.

Metabolism

The pharmacokinetic properties of allogeneic processed thymus tissue are not known.

Route of elimination

The pharmacokinetic properties of allogeneic processed thymus tissue are not known.

Half-life

The pharmacokinetic properties of allogeneic processed thymus tissue are not known.

Clearance

The pharmacokinetic properties of allogeneic processed thymus tissue are not known.

Adverse Effects
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

The LD50 is unknown.

The maximum recommended dose is 22,000 mm2 of allogeneic processed thymus tissue/m2 recipient body surface area (BSA). Standard clinical care is recommended for patients receiving doses higher than the maximum recommended dose. During clinical development, one patient received a dose of 23,755 mm2/m2 and developed enteritis: the biopsy result showed T cell, B cell, and neutrophil infiltration of the gut which resolved after treatment with immunosuppression, five months after treatment with allogeneic processed thymus tissue. Although the clinical understanding of enteritis is unclear, it may be related to the high dose of allogeneic processed thymus tissue.4

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Abatacept.
AdalimumabThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Adalimumab.
AlclometasoneThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Alclometasone.
AldesleukinThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Aldesleukin.
AlefaceptThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Alefacept.
AlemtuzumabThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Alemtuzumab.
AltretamineThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Altretamine.
AmcinonideThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Amcinonide.
AmsacrineThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Amsacrine.
AnakinraThe therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Anakinra.
Interactions
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Rethymic (Enzyvant)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RethymicImplant22000 mm/1IntramuscularEnzyvant Therapeutics Inc.2021-10-08Not applicableUS flag

Categories

Drug Categories
Not Available
Classification
Not classified
Affected organisms
  • Humans

Chemical Identifiers

UNII
XD66YK3YY3
CAS number
Not Available

References

General References
  1. Markert ML, Devlin BH, McCarthy EA: Thymus transplantation. Clin Immunol. 2010 May;135(2):236-46. doi: 10.1016/j.clim.2010.02.007. Epub 2010 Mar 16. [Article]
  2. Chinn IK, Devlin BH, Li YJ, Markert ML: Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2008 Mar;126(3):277-81. doi: 10.1016/j.clim.2007.11.009. Epub 2007 Dec 26. [Article]
  3. Collins C, Sharpe E, Silber A, Kulke S, Hsieh EWY: Congenital Athymia: Genetic Etiologies, Clinical Manifestations, Diagnosis, and Treatment. J Clin Immunol. 2021 Jul;41(5):881-895. doi: 10.1007/s10875-021-01059-7. Epub 2021 May 13. [Article]
  4. FDA Approved Drug Products: RETHYMIC (Allogeneic processed thymus tissue–agdc) For surgical implantation [Link]
  5. Drugs.com: FDA Approves Rethymic [Link]
Wikipedia
Allogeneic_processed_thymus_tissue

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
ImplantIntramuscular22000 mm/1
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Drug created at October 12, 2021 14:49 / Updated at November 28, 2021 16:22