Lauren Howell, PharmD
While the market for new drugs that can treat diabetes has boomed, until recently there has been little news on the prevention front. But in November 2022, FDA approved teplizumab-mzwv (Tzield–Provention Bio, Inc.), the first and only treatment indicated to delay the onset of stage 3 type 1 diabetes (T1D) in patients aged 8 and older.
Recommended dosage and how it works
Teplizumab-mzwv binds to CD3, a cell surface antigen present on T lymphocytes, to delay the onset of stage 3 T1D in patients with stage 2 T1D. The mechanism of action most likely involves 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.
Before treatment with teplizumab-mzwv is initiated, stage 2 T1D must be confirmed by documenting at least 2 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 unavailable. In patients who meet these criteria for diagnosis of stage 2 T1D, it is important to review the patient’s clinical history to ensure that they do not have type 2 diabetes.
Prior to initiating teplizumab-mzwv, a complete blood count and liver enzyme tests should be performed. It is not recommended to use teplizumab-mzwv in patients with a lymphocyte count <1,000 lymphocytes/µL, hemoglobin <10 g/dL, platelet count <150,000 platelets/µL, absolute neutrophil count <1,500 neutrophils/µL, elevated ALT or AST >2 times the upper limit of normal, bilirubin >1.5 times the upper limit of normal, laboratory or clinical evidence of acute infection with Epstein-Barr virus or cytomegalovirus, or active serious infection or chronic active infection other than localized skin infections. Teplizumab-mzwv must be diluted in 0.9% sodium chloride injection. Patients need to be premedicated with an NSAID or acetaminophen, an antihistamine, and an antiemetic before each teplizumab-mzwv dose for at least the first 5 days of the 14-day treatment course. Administration of teplizumab-mzwv should occur by I.V. infusion, over a minimum of 30 minutes, once daily for 14 consecutive days.
Teplizumab-mzwv is packaged in a 2 mg/2 mL single-dose vial. The recommended dose is
- 65 mcg/m2 on day 1
- 125 mcg/m2 on day 2
- 250 mcg/m2 on day 3
- 500 mcg/m2 on day 4
- 1,030 mcg/m2 on days 5–14
Two doses should not be administered on the same day.
Drug interactions
The safety of immunization with live-attenuated vaccines in patients treated with teplizumab-mzwv has not been studied. Teplizumab-mzwv may interfere with the immune response to vaccination and decrease vaccine efficacy. All age-appropriate vaccines should be administered prior to starting teplizumab-mzwv.
Inactivated or mRNA vaccinations should not be administered within the 2 weeks prior to teplizumab-mzwv treatment, during treatment, or 6 weeks after completion of treatment. Live-attenuated vaccinations should not be administered within the 8 weeks prior to teplizumab-mzwv treatment, during treatment, or up to 52 weeks after treatment.
Adverse effects and contraindications
The most common adverse reactions in patients treated with teplizumab-mzwv were lymphopenia, rash, leukopenia, and headache. Currently, there are no contraindications to teplizumab-mzwv.
Patient counseling
Patients should be informed about the signs and symptoms of cytokine release syndrome, infection, and hypersensitivity reactions. Pregnant patients and patients of reproductive potential should be advised that teplizumab-mzwv may cause fetal harm. A lactating patient may consider pumping and discarding breast milk during and for 20 days after teplizumab-mzwv administration. ■