General Information

Tzield (teplizumab-mzwv) is a CD3-directed antibody.

Tzield is specifically indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adults and pediatric patients aged 8 years and older with Stage 2 T1D.

Tzield is supplied as a solution for intravenous administration. 

Prior to administration:

• 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 type 1 diabetes, ensure the clinical history of the patient does not suggest type 2 diabetes.
• Obtain a complete blood count and liver enzyme tests. Use of Tzield is not recommended in patients with certain laboratory abnormalities
• Must dilute Tzield in 0.9% Sodium Chloride Injection
• Pre-medicate with: (1) a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen, (2) an antihistamine, and/or (3) an antiemetic before each Tzield dose for at least the first 5 days of the 14-day treatment course

Administer Tzield by intravenous infusion (over a minimum of 30 minutes) once daily for 14 days as follows: 

• Day 1: 65 mcg/m2
• Day 2: 125 mcg/m2
• Day 3: 250 mcg/m2
• Day 4: 500 mcg/m2
• Days 5 through 14: 1,030 mcg/m2
• Do not administer two doses on the same day

Mechanism of Action

Tzield (teplizumab-mzwv) binds to CD3 (a cell surface antigen present on T lymphocytes) and delays the onset of Stage 3 type 1 diabetes in adults and pediatric patients aged 8 years and older with Stage 2 type 1 diabetes. 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.

Side Effects

Adverse effects associated with the use of Tzield may include, but are not limited to, the following:

• lymphopenia
• rash
• leukopenia
• headache

Tzield is associated with the following serious risks: Cytokine Release Syndrome (CRS). Serious Infections: Use of Tzield is not recommended in patients with active serious infection or chronic infection. Lymphopenia: Monitor white blood cell counts during the treatment period. Hypersensitivity Reactions. Vaccinations: Administer all age-appropriate vaccinations prior to starting Tzield. See recommendations regarding live-attenuated, inactivated, and mRNA vaccines.

Clinical Trial Results 

The FDA approval was based on the TN-10 Study, a pivotal randomized, double-blind, event driven, placebo controlled clinical trial which evaluated Tzield for the delay of T1D (Stage 3, or clinical T1D) in Stage 2 T1D patients, defined by the presence of two or more T1D-related autoantibodies and dysglycemia. Seventy-six patients ages 8 to 49 (72% under the age of 18) were randomized to receive a single 14-day course of either teplizumab (n=44) or placebo (n=32) by IV infusion. The primary efficacy endpoint in this study was the time from randomization to development of Stage 3 T1D diagnosis.

Stage 3 T1D was diagnosed in 20 (45%) of the Tzield-treated patients and in 23 (72%) of the placebo-treated patients. When analyzed by time to Stage 3 T1D diagnosis, stratified by age and oral glucose tolerance test status at randomization, the median time from randomization to Stage 3 T1D diagnosis was 50 months in the Tzield group and 25 months in the placebo group, for a difference of 25 months. With a median follow-up time of 51 months, therapy with Tzield resulted in a statistically significant delay in the development of Stage 3 T1D.