Teplizumab

TZIELD is indicated to: Delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients 1 year of age and older with Stage 2 T1D. Delay the decline in endogenous insulin production in pediatric patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. This indication is approved under accelerated approval based on evidence of reduced C-peptide decline. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use: There is limited evidence of safety and effectiveness in patients aged 45 years and older with Stage 2 T1D. TZIELD is not effective as a disease modifying therapy in non-autoimmune dysglycemic conditions.

Teplizumab-mzwv binds to CD3 (a cell surface antigen present on T lymphocytes) and delays the onset of Stage 3 T1D in adult and pediatric patients aged 1 year and older with Stage 2 T1D and delays the decline in endogenous insulin production in patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. The mechanism may involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes. Teplizumab-mzwv leads to an increase in the proportion of regulatory T cells and of exhausted CD8+ T cells in peripheral blood.

Confirm Stage 2 T1D by documenting at least two positive pancreatic islet autoantibodies in those who have dysglycemia without overt hyperglycemia using an oral glucose tolerance test (OGTT) or alternative method if appropriate and OGTT is not available. In patients who meet criteria for a diagnosis of Stage 2 T1D ensure the patient's diagnosis confirms an autoimmune origin and does not suggest insulin resistance due to obesity, type 2 diabetes (T2D) or dysglycemia due to other forms of diabetes. Confirm Stage 3 T1D by documenting at least one positive pancreatic islet cell autoantibody and peak C-peptide ≥0.2 pmol/mL on a mixed-meal tolerance test (MMTT) or alternative method if appropriate and MMTT is not available.

TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection).

WARNING: Viral Reactivation Serious, life-threatening cases of viral reactivation, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation have been reported with TZIELD. Patients who are immunocompromised are at increased risk. Serious cases have also been reported in adults with higher body surface area or comorbid conditions, such as adrenal insufficiency or cardiovascular disease. Cytokine Release Syndrome (CRS): Premedicate, monitor liver enzymes and bilirubin during treatment, and discontinue in those that develop elevated ALT or AST more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN. If severe CRS develops, consider temporarily pausing or discontinuing TZIELD. Serious Infections: Use of TZIELD is not recommended in patients with active serious infection or chronic infection.

The following serious adverse reactions are described elsewhere in the Prescribing Information: Viral Reactivation Cytokine Release Syndrome Serious Infections Lymphopenia Hypersensitivity Reactions Most common adverse reactions were lymphopenia, vomiting, rash, leukopenia, diarrhea, neutropenia, increased liver transaminase and headache.

Do not freeze or shake the vials. Store upright.