The Food and Drug Administration has approved the Biologics License Application for Rethymic® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for immune reconstitution in pediatric patients with congenital athymia.
Rethymic is intended to reconstitute immunity in patients who are athymic; it is administered by a surgical procedure where it is implanted in the quadriceps muscle. The proposed mechanism of action involves the migration of recipient T cell progenitors from the bone marrow to the implanted Rethymic slices (defined as the contents on a single filter membrane), where they develop into naïve immunocompetent recipient T cells.
The approval was based on data from 10 prospective, single-center, open-label clinical studies that included a total of 105 patients aged 1 month to 16 years with congenital athymia. Each patient received a single administration of Rethymic.
Among the 95 patients in the efficacy analysis set, results showed that the Kaplan-Meier estimates of survival following treatment were 77% (95% CI, 0.670-0.841) at year 1 and 76% (95% CI, 0.658-0.832) at year 2. For patients alive after 1 year of treatment, the Kaplan-Meier estimated long-term survival rate was 94% at a median follow-up time of 10.7 years. Rethymic also reduced the number of infections over time during the first 2 years after treatment (P <.001).
The most common adverse reactions with Rethymic included hypertension (19%) cytokine release syndrome (18%), rash (15%), hypomagnesemia (16%), renal impairment/failure (12%), thrombocytopenia (12%), and graft versus host disease (10%).
Rethymic is unlikely to provide immune reconstitution sufficient to protect from infection prior to 6 to 12 months post implantation. Patients and health care providers should be advised to follow infection control measures until the development of thymic function can be established.
Rethymic is supplied ready for use as slices of processed thymus tissue, in sterile, polystyrene dishes; each drug product dish contains up to 4 Rethymic slices. Dosing is individualized and determined by the total surface area of the Rethymic slices and the body surface area of the patient. At the time of surgery, the manufacturing personnel communicate to the surgical team the portion of the product that represents the minimum dose.
- FDA approves innovative treatment for pediatric patients with congenital athymia. News release. US Food and Drug Administration. Accessed October 12, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-treatment-pediatric-patients-congenital-athymia.
- Enzyvant receives FDA approval for Rethymic® (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for pediatric congenital athymia. News release. Enzyvant Therapeutics, Inc. Accessed October 12, 2021. https://www.globenewswire.com/news-release/2021/10/09/2311432/0/en/Enzyvant-Receives-FDA-Approval-for-RETHYMIC-allogeneic-processed-thymus-tissue-agdc-a-One-Time-Regenerative-Tissue-Based-Therapy-for-Pediatric-Congenital-Athymia.html.
- Rethymic. Package Insert. Enzyvant Therapeutics, Inc.; 2021. Accessed October 12, 2021. https://enzyvant.com/wp-content/uploads/2021/10/prescribing-information.pdf.