Clinical trial results

RETHYMIC greatly improved survival for patients with congenital athymia1

The efficacy and safety of RETHYMIC were evaluated in 105 pediatric patients across 10 open-label, prospective, single-center clinical trials, including 95 patients in the primary efficacy analysis, with a follow-up of up to 25.5 years.1,2

Patient demographics1

Characteristic

Primary Efficacy Analysis (N=95)

Median (range) age at the time of treatment, months

9 (1-36)

Male, %

59

Race, %

White

Black

Asian/Pacific Islander

American Indian/Alaskan Native

Multi-race

70

22

4

2

2

Associated conditions, %

22q11.2 deletion

CHARGE syndrome

FOXN1 deficiency

TBX variant

38

24

2

1

Diagnosed with complete DiGeorge syndrome*, %

Typical

Atypical*

53

44

*These patients may have had a rash, lymphadenopathy, or oligoclonal cells.1

Survival rates

Primary and supportive endpoints: Kaplan-Meier estimated survival rates were 77% (95% CI, 0.670, 0.841) at year 1 and 76% (95% CI, 0.658, 0.832) at year 2.1,2

Survival by Year1

For patients who were alive at 1 year after treatment, the survival rate was

with a median follow-up of 10.7 years1

In a natural history study, congenital athymia patients on supportive care alone typically did not survive beyond 2 to 3 years of age.1

Immune system development

Secondary endpoint: Naive CD4+ and CD8+ T cells reconstituted over the first year following treatment and increased through year 2.1,2

Development of Naive T Cells Following Treatment1,2

Baseline

Median naive CD4+ T cells/mm3(min, max)Number of subjects

1.0 (0, 38)63

Median naive CD8+ T cells/mm3(min, max)Number of subjects

0 (0, 46)60

Month 6

Median naive CD4+ T cells/mm3(min, max)Number of subjects

42 (0, 653)62

Median naive CD8+ T cells/mm3(min, max)Number of subjects

9 (0, 163)53

Month 12

Median naive CD4+ T cells/mm3(min, max)Number of subjects

212 (1, 751)42

Median naive CD8+ T cells/mm3(min, max)Number of subjects

58 (0, 304)37

Month 24

Median naive CD4+ T cells/mm3(min, max)Number of subjects

275 (33, 858)26

Median naive CD8+ T cells/mm3(min, max)Number of subjects

86 (6, 275)26

Immune reconstitution sufficient to protect against infection is unlikely to develop prior to 6 to 12 months after treatment, and for some patients, may take up to 2 years.1

Infection reduction

RETHYMIC significantly decreased the rate of infections in the first 2 years after treatment.1

AT 6 TO ≤12 MONTHS AFTER TREATMENT,

38%

fewer patients
experienced an infection event

vs 0 to ≤6 months after treatment (P<0.001)1

AT 12 TO ≤24 MONTHS AFTER TREATMENT,
THERE WAS A MEAN DIFFERENCE OF

2.9

events per patient

vs 0 to ≤12 months after treatment (P<0.001)1

The safety of RETHYMIC was demonstrated in 105 patients across 10 clinical trials1

The most common (≥10%) adverse reactions related to RETHYMIC were hypertension, cytokine release syndrome, hypomagnesemia, rash, renal impairment/failure, thrombocytopenia, and graft versus host disease (GVHD).1

Adverse reactions occurring in at least 5% of patients in the first 2 years after treatment1

System organ class

RETHYMIC (N=105)
n (%)

Number of patients with adverse reactions

80 (76)

Hypertension

20 (19)

Cytokine release syndrome

All events occurred in association with anti-thymocyte globulin [rabbit] treatment

19 (18)

Hypomagnesemia

17 (16)

Rash,

granuloma skin, rash papular, and urticaria

16 (15)

Renal impairment/failure,

acute kidney injury, proteinuria, and increased blood creatinine

13 (12)

Thrombocytopenia,

and immune thrombocytopenic purpura

13 (12)

Graft versus host disease,

GVHD-gut, GVHD-skin, and Omenn syndrome

11 (10)

Hemolytic anemia,

autoimmune hemolytic anemia, Coombs-positive hemolytic anemia, and hemolysis

9 (9)

Neutropenia

9 (9)

Respiratory distress,

hypoxia, and respiratory failure

8 (8)

Proteinuria

7 (7)

Pyrexia

6 (6)

Acidosis,

renal tubular acidosis, and decreased blood bicarbonate

6 (6)

Diarrhea,

and hemorrhagic diarrhea

5 (5)

Seizure,

infantile spasms, and febrile convulsions

5 (5)

Of the 105 patients in the clinical studies, 29 died, including 23 in the first year. The majority of deaths in the first year after receiving RETHYMIC were due to infections (13).1

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Unlike a transplant, RETHYMIC is engineered for one patient at a time through a complex process using donor thymus tissue.1,3

Learn how it's made
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See what you should expect after your patients receive treatment with RETHYMIC.

Explore post-treatment care
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Enzyvant 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

Immune reconstitution sufficient to protect from infection is unlikely to develop prior to 6-12 months after treatment with RETHYMIC. Given the immunocompromised condition of athymic patients, follow infection control measures until the development of thymic function is established as measured through flow cytometry. 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 specified criteria are met, and two months after stopping, IgG trough level should be checked. Prior to and after treatment with RETHYMIC, patients should be maintained on Pneumocystis jiroveci pneumonia prophylaxis until specified criteria are met.

RETHYMIC may cause or exacerbate pre-existing graft versus host disease (GVHD). Monitor and treat patients at risk for the development of GVHD. Risk factors for GVHD include atypical complete DiGeorge anomaly phenotype, prior hematopoietic cell transplantation (HCT) and maternal engraftment. GVHD may manifest as fever, rash, lymphadenopathy, elevated bilirubin and liver enzymes, enteritis, and/or diarrhea.

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 for the development of autoimmune disorders, including complete blood counts with differential, liver enzymes, serum creatinine, urinalysis, and thyroid function.

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

In the clinical studies of RETHYMIC, 4 out of 4 patients with pre-existing cytomegalovirus infection died. The benefits/risks of treatment should be considered prior to treating patients with pre-existing CMV infection.

Because of the underlying immune deficiency, patients who receive RETHYMIC may be at risk of developing post-treatment lymphoproliferative disorder. Patients should be monitored for the development of lymphoproliferative disorder.

Transmission of infectious disease may occur because RETHYMIC is derived from human tissue and because product manufacturing includes porcine- and bovine-derived reagents.

Immunizations should not be administered in patients who have received RETHYMIC until immune-function criteria have been met.

All patients should be screened for anti-HLA antibodies prior to receiving RETHYMIC. Patients testing positive for anti-HLA antibodies should receive RETHYMIC from a donor who does not express those HLA alleles. HLA matching is required in patients who have received a prior HCT or a solid organ transplant. Patients who have received a prior HCT are at increased risk of developing GVHD after RETHYMIC if the HCT donor did not fully match the recipient.

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

The most common (>10%) adverse events related to RETHYMIC included: hypertension, cytokine release syndrome, rash, hypomagnesemia, renal impairment/failure, thrombocytopenia, and graft versus host disease.

To report suspected adverse reactions, please contact the FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch

Indication

RETHYMIC® (allogeneic processed thymus tissue–agdc) 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).

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Sumitomo Pharma is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO is a registered trademark of Sumitomo Chemical Co., Ltd., used under license. Sumitomo Pharma America, Inc. is a U.S. subsidiary of Sumitomo Pharma Co. Ltd. ENZYVANT CONNECT®, RETHYMIC®, and their logos are registered trademarks of Enzyvant Therapeutics GmbH. © 2023 Enzyvant Therapeutics GmbH. All rights reserved. US—2300143 11/2023