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Enzyvant CONNECT is a program that provides patients and caregivers personalized support throughout the treatment journey.

For more information, call 844-ENZCNCT (844-369-2628), Monday through Friday, 8:00 AM to 8:00 PM ET. or download the Patient Enrollment Form to enroll your patient. The form will require your signature, and the signature of parent or legal guardian of your patient.

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a guide through the
congenital athymia journey
for healthcare providers

Congenital athymia is an ultra-rare condition characterized by the absence of a thymus at birth1. Estimated incidence in the United States is approximately 17 to 24 infants for every 4 million live births per year2.

Click the buttons below to learn more.

Congenital athymia results
in immunodeficieny and immune
dysregulation1,3

Learn about the diagnostic pathway for congenital athymia, including how to differentiate it from Severe Combined Immunodeficiency (SCID), and about the different phenotypes of congenital athymia.

Congenital Athymia

What is Congenital Athymia?

Congenital athymia is an ultra-rare primary immunodeficiency which is characterized by the lack of a functional thymus at birth. Congenital athymia results in profound immunodeficiency and immune dysregulation1,3. The clinical manifestations are a direct result of the absence of the thymus and the inability to produce immunocompetent T cells, leading to increased susceptibility to infection. These infections and autoimmune conditions can be fatal, and with only supportive care, children with congenital athymia typically do not survive beyond 2 to 3 years of age4.

The thymus

The thymus is the only organ where thymocytes can mature, be selected, and ultimately survive to become naïve T cells. Although T cells originate in the bone marrow as progenitor cells, the bone marrow is not equipped with specialized tissue required for T cell maturation1. T cell progenitors emerging from the bone marrow migrate to the thymus for maturation, where they are selected to become naïve T cells via positive and negative selection. Some progenitor cells begin to express CD4 or CD8 receptors. Subsequent downregulation of CD4 or CD8 results in development of naïve single positive cells that can exit the thymus and enter the peripheral bloodstream1.

What conditions are associated with congenital athymia?

Congenital athymia may be associated with other conditions such as: DiGeorge syndrome (22q11.2 deletion syndrome); Mutations in the genes TBX1, CHD7, (CHARGE syndrome), and FOXN1 (FOXN1 deficiency); Diabetic embryopathy1, 3, 6. These multi-faceted conditions and syndromes make the already complex diagnosis of congenital athymia even more challenging.

Newborn screening

Congenital athymia is initially detected through T cell receptor rearrangement excision cell circle (TREC) screening1. This test will identify infants who may have congenital athymia in addition to severe combined immunodeficiency (SCID) and is required in all 50 US states for all newborns since 20181. TREC screening is critical as it provides the first indication of an immunologic issue in an infant’s T cell development. Low TREC levels indicate the need for further testing6. Flow cytometry may show low levels of naive T cells and may help strengthen the diagnosis of congenital athymia1.

Congenital athymia and Severe Combined Immunodeficiency (SCID) are both primary immunodeficiencies, but they are different1. Congenital athymia may be mistaken for SCID, as very low T cell counts are present in both conditions.

Patients with congenital athymia lack T cells but have normal numbers of B cells and NK (natural killer) cells. They present with a T-B+NK+ phenotype. However, a complicating factor is that a subset of patients with SCID also present with a T-B+NK+ phenotype. Additional steps to confirm the diagnosis may be required if a genetic cause of athymia is not identified1. SCID is a group of disorders rooted in the dysfunction of hematopoietic stem cells of the bone marrow, not in dysfunction or absence of the thymus. Additionally, patients with SCID may lack B cells or have impaired B-cell development1. In contrast, B-cell numbers are normal in patients with congenital athymia. Lack of B cells is an important clue that the patient may have SCID. Below is a schematic of the diagnostic pathway including steps for how to differentiate athymia from SCID.

The sooner congenital athymia is identified, the sooner isolation and infection prevention measures can be initiated and the less likely a patient is to be treated with therapies that may not be effective in congenital athymia.

What is the difference between typical and atypical phenotypes in congenital athymia?

There are 2 phenotypes of congenital athymia: typical and atypical8. The typical phenotype is characterized by profound T cell lymphopenia, absence of rash or lymphadenopathy, and lack of mitogen-stimulated T cell proliferation3,8. The atypical phenotype frequently presents with signs and symptoms of autologous GVHD, such as rash, lymphadenopathy, high numbers of circulating T cells (from oligoclonal T cell expansion), and T-cell proliferation in response to mitogens (eg, phytohemagglutinin)1.

Often, the expanded oligoclonal T cells infiltrate the skin, gut, and other organs8. Biopsy of the inflammatory rash in patients with atypical congenital athymia shows T cell infiltrates1. Some patients with typical congenital athymia will, over time, develop the atypical phenotype8.

Understanding Congenital Athymia

Download

Indication and Important Safety Information

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).

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, 3 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

US–1900016

US–2100095

Supportive care is an established
approach for patients with
congenital athymia.

Supportive care relies primarily on established isolation protocols which can be adapted for the patients home. It is important to educate parents and caregivers on the reasons for supportive care and to provide information on what they can do inside and outside the home to protect their child.

Supportive Care

Prior to the availability of RETHYMIC® (allogeneic processed thymus tissue–agdc), the standard of care for congenital athymia was limited to supportive care. Supportive care consists of isolation, prophylaxis antimicrobials, immunoglobulins, and sometimes immunosuppression.

Prior to receiving RETHYMIC, patients need to be maintained on supportive care. Supportive care needs to be maintained for as long as needed until immune reconstitution occurs which can take up to 2 years.

Understanding Congenital Athymia

Download

Indication and Important Safety Information

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).

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, 3 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

US–1900016

US–2100095

Treatment with RETHYMIC

RETHYMIC® (allogeneic processed thymus tissue–agdc) is indicated for immune reconstitution in pediatric patients with congenital athymia.

RETHYMIC is not for use in patients who have been diagnosed with severe combined immunodeficiency (SCID).

Treatment with RETHYMIC® (allogeneic processed thymus tissue–agdc)

RETHYMIC Clinical Trial Design

The safety and efficacy of RETHYMIC was evaluated in 105 patients across 10 clinical trials. The effectiveness of RETHYMIC was evaluated in 95 of those patients with congenital athymia in 10 clinical trials with follow-up of up to 25.5 years5.

The primary end point of the analysis was the Kaplan Meier estimated survival at one year post administration of RETHYMIC. Kaplan Meier estimated survival at two years post treatment was a supportive endpoint. Secondary endpoints included naïve and total T cell numbers and function at one year post treatment. Reductions in the number of infections over time and survival in patients alive one year post treatment were also analyzed.

Natural History Population

Without treatment, congenital athymia is fatal in childhood. A natural history population was observed from 1991 through 2017 in which 49 patients diagnosed with congenital athymia received supportive care only5. The 2-year survival rate was 6%, with all patients dying by 3 years of age.

RETHYMIC Efficacy

The Kaplan-Meier estimated survival rates at year 1 and year 2 were 77% (95% CI, 0.670-0.841) and 76% (95% CI, 0.658-0.832), respectively5.

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 years5.

Immune System Development

Naive CD4 and CD8T cells reconstituted over the first year following treatment and increased through year 2. Immune reconstitution sufficient to protect from infection is unlikely to develop prior to 6-12 months after treatment with RETHYMIC5.

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 2-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 to12 to ≤24 months after treatment. There was a mean difference of 2.9 events (P<0.001) per patient5.

Adverse Reactions

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. The following table lists the adverse reactions occurring in 105 patients who were treated with RETHYMIC in these studies5.

The most common (>10%) adverse events related to RETHYMIC included:

  • Hypertension (high blood pressure, 19%)
  • Cytokine release syndrome (18%)
  • Rash (15%)
  • Hypomagnesemia (low magnesium, 16%)
  • Renal impairment / failure (decrease of kidney function, 12%)
  • Thrombocytopenia (low platelets, 12%)
  • Graft versus host disease (10%)

Please See the Important Safety Information for RETHYMIC below.

RETHYMIC Dosage and Administration

The recommended dose range is 5,000 to 22,000 mm2 of RETHYMIC/m2 recipient body surface area (BSA).

RETHYMIC is surgically implanted in one (or both, if necessary) of the patient’s quadriceps muscles during a single surgical procedure. The quadriceps muscle is used as the implantation site due to its high vascularization5.

RETHYMIC administration and development of patients T cells5.

Following administration, capillaries grow from the muscle into RETHYMIC, providing oxygen and nutrients migrating to RETHYMIC, the bone marrow stem cells develop into naive, immunocompetent T cells3.

For patients who respond to RETHYMIC, a diverse T cell population is established. Immune reconstitution sufficient to protect from infection is unlikely to develop prior to 6 to 12 months after treatment with RETHYMIC5. For some patients elevated naïve T cell numbers are not observed until 2 years after treatment. Supportive care measures should be continued until immune reconstitution is established.

HCP RETHYMIC Brochure

Download

After Treatment

Patients will need to be monitored while their immune system begins to reconstitute. Here are monitoring recommendations and see the RETHYMIC prescribing information for further information.

How long does it take for RETHYMIC to work?

Immune reconstitution sufficient to protect from infection is unlikely to develop prior to 6-12 months after treatment with RETHYMIC5. For some patients elevated naïve T cell numbers are not observed until 2 years after treatment. Supportive care measures should be continued until immune recons is established.

What monitoring needs to be in place?

Monitoring should be performed regularly during the period the immune system is restored. T cell counts should be checked by flow cytometry every 3 months and, as numbers rise, used to guide weaning of5:

  • Immunosuppression
  • Prophylaxis for pneumocystis
  • Reverse isolation

For additional information on monitoring, please see prescribing information.

When can the patient receive vaccines?

Immunizations should not be administered in patients who have received RETHYMIC until immune-function criteria have been met. Inactivated vaccines may be administered once all of the following criteria are met5:

  • Immunosuppressive therapies have been discontinued
  • Immunoglobulin (IgG) replacement therapy has been discontinued
  • The total CD4+ T cell count is > 200 cells/mm3 and there are more CD4+ T cells than CD8+ T cells (CD4+ > CD8+)
  • It is recommended that no more than 2 inactivated vaccines be given per month.

Live virus vaccines should not be administered until patients have met the criteria for inactivated vaccines and received vaccinations with inactivated agents (eg, tetanus toxoid). No additional vaccines (live or inactivated), except the inactivated influenza vaccine, should be given within 6 months after vaccination with a measles containing vaccine or within 2 months after the varicella vaccine. Consider verifying response to vaccination with appropriate testing, in particular varicella and measles5.

When can my patient discontinue immunosuppresants?

Patients can be weaned off immunosuppression when at least 10% of CD3+ T cells are naïve in phenotype3.

When can my patient discontinue IgG replacement therapy?

Patients should be maintained on immunoglobulin replacement therapy until all of the following criteria are met:

  • No longer on immunosuppression (at least 10% of CD3+ T cells are naïve in phenotype).
  • At least 9 months post-treatment.
  • Phytohemagglutinin (PHA) response within normal limits.
  • Normal serum IgA is also desirable but not required.
  • Two months after stopping immunoglobulin replacement therapy, the IgG trough level should be checked.
  • If the IgG trough level is in the normal range for age, the patient can remain off of immunoglobulin replacement.
  • 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
When can my patient discontinue prophylaxis for pneumocystis?

Prior to and after treatment with RETHYMIC, patients should be maintained on Pneumocystis jiroveci pneumonia prophylaxis until all of the following criteria are met5:

  • No longer on immunosuppression (at least 10% of CD3+ T cells are naïve in phenotype).
  • At least 9 months post-treatment.
  • PHA response within normal limits.
  • CD4+ T cell count > 200 cells/mm3.
How long should isolation continue?

As immunity builds and reaches thresholds for fighting off infection, you may guide families in ending strict isolation. Less restrictive isolation may continue as T cell levels continue to rise and additional milestones are reached. restrictive isolation may continue as T cell levels continue to rise and additional milestones are reached5,7.

Indication and Important Safety Information

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).

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, 3 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

US–1900016

US–2100095

How To Access RETHYMIC® (allogeneic processed thymus tissue–agdc)

RETHYMIC is currently available at one location in Durham, North Carolina. This section provides additional information on how to access RETHYMIC for your patient.

How To Access RETHYMIC® (allogeneic processed thymus tissue–agdc)

To obtain the contact information for the single site of administration in Durham, North Carolina, please contact Enzyvant Medical Information at +1 833 369 9868 (833-ENZYVNT) or [email protected]. You can enroll your patient in Enzyvant CONNECT, a program that provides support to patients and families through the treatment journey. Click here for more information.

Where is RETHYMIC available?

RETHYMIC is currently available at one location in Durham, North Carolina. Your patient will need to travel to North Carolina for the administration procedure.

How do I access RETHYMIC for my patient?

Contact Enzyvant Medical Information at +1 833 369 9868 (833-ENZYVNT) or [email protected] to discuss treatment with RETHYMIC.

Why is the supply of RETHYMIC limited?

Supply is limited by the availably of donor thymus tissue. Each lot of RETHYMIC is made one patient at a time.

When will my patient be treated?

Enzyvant does not make treatment decisions. Enzyvant’s role is to supply RETHYMIC. For more information, contact Enzyvant Medical Information at +1 833 369 9868 (833-ENZYVNT) or [email protected].

Indication and Important Safety Information

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).

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, 3 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

US–1900016

US–2100095

Supporting the treatment journey

Enzyvant CONNECT is a program that provides patients and caregivers personalized support throughout the treatment journey.

The Enzyvant CONNECT team will assist families with:
  • Navigating insurance information
  • Connecting to financial assistance programs
  • Providing educational resources
Enroll your patient today!

Call us today at 844-ENZCNCT (844-369-2628), 8:00 AM to 8:00 PM ET. Complete and submit the Patient Enrollment Form to get started. The form will require your signature, and the signature of a parent or legal guardian of your patient.

Meet The Enzyvant CONNECT Team

Patient Access Specialist – The dedicated Patient Access Specialist will assist patients and caregivers with:

  • Insurance information – Benefit investigation/verification to determine insurance coverage, any related requirements, and out-of-pocket responsibility.
  • Financial assistance programs – Help identify and put patients and caregivers in touch with programs that may be able to help with financial and/or support assistance.
  • Educational resources – Provide information about congenital athymia and treatment, and advocacy resources to support patients and caregivers along the treatment journey.

Support Liaison – The Support Liaison is another resource available to everyone enrolled in Enzyvant CONNECT. The Support Liaison can provide information about congenital athymia and available educational resources. The Support Liaison is here to help before and after RETHYMIC treatment. The Support Liaison can also connect families with advocacy organizations.

Access and Support for Families

After you complete and submit your patient’s enrollment form, a Patient Access Specialist from Enzyvant CONNECT will contact your patient’s family and will schedule a welcome call to review next steps and answer questions.

Download Enrollment Form

healthcare PROVIDER RESOURCES

As you discuss the care of your patient with their family or caregiver, you may find these materials and organizations helpful.

For Healthcare Providers
For Caregivers

  • Understanding Congenital Athymia

    Download


  • Congenital Athymia Questions to Ask your Doctor

    Download


  • Congenital Athymia: Information for Family and Friends

    Download

  • \

    Caring for a Child with Congenital Athymia

    Download

Medical Literature

These articles are provided by Enzyvant for your education and for discussion of FDA-approved use. RETHYMIC (allogenic processed thymus tissue-agdc) should only be used according to the accompanying complete prescribing information.

LANDMARK STUDY

Experience with cultured thymus tissue in 105 children

Journal of Allergy and Immunology

Read Full Text
See RETHYMIC Full Prescribing Information

Care of Children with DiGeorge Before and After Cultured Thymus Tissue Implantation

Journal of Clinical Immunology

Read Full Text
See RETHYMIC Full Prescribing Information

Congenital Athymia: Genetic Etiologies, Clinical Manifestations, Diagnosis and Treatment

Journal of Clinical Immunology

Read Full Text
See RETHYMIC Full Prescribing Information

Defining Clinical, Emotional, Social and Financial Burden of Congenital Athymia

Journal of Medical Economics

Read Full Text
See RETHYMIC Full Prescribing Information

Organizations

Although no organizations are dedicated specifically to congenital athymia, there are several for patients with immune system diseases that provide valuable support and education. These organizations, independent from Enzyvant, include the following:

Jeffrey Modell Foundation

This nonprofit organization helps families and caregivers affected by immunodeficiency disorders find support, education, awareness,
advocacy and care.

Visit Site

Global Genes

This organization pursues positive change and aims to connect, empower, and inspire the rare disease community.

Visit Site

Immune Deficiency Foundation

Here you can find valuable information and insights related to immunodeficiency disorders, including the Patient and Family Handbook for Primary Immunodeficiency Diseases.

Visit Site

National Organization of Rare Disorders

This patient advocacy organization, along with its more than 300 patient organization members, is committed to the identification, treatment, and cure of rare disorders through the programs of education, advocacy, research and patient services.

Visit Site

Indication and Important Safety Information

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).

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, 3 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

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Indication and Important Safety Information (ISI)

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).

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, 3 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

US--1900016

US--2100095

1. Collins C, Sharpe E, Silber A, Kulke S, Hsieh EWY. Congenital athymia: genetic etiologies, clinical manifestations, diagnosis, and treatment. J Clin Immunol. 2021;41(5):881-895. doi.org/10.1007/s10875-021-01059-7

2. Data on file, Enzyvant.

3. Markert ML, Gupton SE, McCarthy EA. Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol. Published online August 3, 2021. doi:10.1016/j.jaci.2021.06.028

4. Hsieh EWY, Kim-Chang JJ, Kulke S, Silber A, O’Hara M, Collins C. Defining the clinical, emotional, social, and financial burden of congenital athymia. Adv Ther. 2021;38(8):4271-4288. doi.org/10.1007/s12325-021-01820-9

5. RETHYMIC [package insert]. Cambridge, MA: Enzyvant Therapeutics, Inc; 2021.

6. Markert ML. Defects in thymic development. In: Sullivan KE, Stiehm ER, eds. Stiehm’s Immune Deficiencies. 2nd ed. New York, NY: Elsevier; 2020:357-379.

7. Gupton SE, McCarthy EA, Markert ML. Care of children with DiGeorge before and after cultured thymus tissue implantation. J Clin Immunol. 2021;41(5):896-905. doi.org/10.1007/s10875-021-01044-0

8. Markert ML, Devlin BH, Alexieff MJ, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007;109(10):4539-4547.

9. Markert ML, McCarthy EA, Gupton SE, Lim AP. Cultured thymus tissue transplantation. In: Sullivan KE, Stiehm ER, eds. Stiehm's Immune Deficiencies. 2nd ed.: Academic Press; 2020:1229-1239.