The U.S. Food and Drug Administration approved Provention Bio’s Tzield™ (teplizumab-mzwv) on November 17, 2022, to delay the onset of Stage 3 type 1 diabetes (T1D) in adults and children eight years of age and older who currently have Stage 2 T1D. Tzield is an anti-CD-3 specific monoclonal antibody that binds to and eliminates autoreactive T-cells, which leads to autoantibodies that destroy β-cells in the islets of Langerhans of the pancreas while sparing regulatory T-cells. Following premedication with a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen, an antihistamine, and an anti-emetic, Tzield is infused over 30 minutes based on body surface area once daily for 14 consecutive days. It is supplied as a 2mg/2mL clear and colorless single-dose solution in a vial that must be diluted with 0.9% sodium chloride. Sanofi will be co-promoting Tzield in the U.S.; the launch date has not yet been announced. For full prescribing information see here.
At a Glance
- Brand (Generic) Name: Tzield (teplizumab-mzwv)
- Manufacturer: Provention Bio
- Date Approved: Nov. 17, 2022
- Indication: to delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients aged eight years and older with Stage 2 T1D
- Dosage Forms Available: single-dose vials containing 2mg/2mL in a colorless solution for dilution and intravenous (IV) infusion
- Launch Date: not known at this time
- Estimated Annual Cost: The average cost for the 14-day treatment is expected to be approximately $194,000.
- Over 1.8 million Americans have T1D, an autoimmune disease in which the β-cells of the pancreas make little or no insulin.
- Over 75% of people with T1D have poor control of their blood glucose levels, considered an HbA1c level >7%. Poor control leads to complications that can result in kidney disease, cardiovascular disease, retinopathy, and metabolic syndrome.
- Around half of the newly diagnosed patients with T1D present with diabetic ketoacidosis, a life-threatening condition.
- Provention Bio estimates that there are approximately 30,000 patients in the U.S. who may be candidates for treatment with Tzield.
- Tzield may delay the onset of disease in high-risk individuals who have Stage 2 T1D, as determined by two positive pancreatic islet autoantibodies tests and abnormal blood glucose levels without evident high blood sugar using an oral glucose tolerance test (OGTT). This stage should not be confused with type 2 diabetes. It is important to distinguish the patient’s clinical history since Tzield is not approved for that indication.
- There is a genetic predisposition to inheriting T1D and an environmental trigger that leads to certain autoantibodies that lead to the self-destruction of the β-cells in the islets of Langerhans of the pancreas. Caucasians have the highest rate of inheriting T1D, mostly due to the presence of autoimmune-related HLA-DR3 and HLA-DR4 genes. Known environmental triggers are not certain, however, it is believed that around 60% of cases are associated with coxsackievirus B infection. Other environmental triggers can include living in cold weather climates and dieting early in life.
- In its pivotal trial, 76 patients aged eight years to 49 years, who had two or more T1D autoantibodies and dysglycemia, were given teplizumab or a placebo. At the 2.5-year follow-up, 50% of teplizumab-treated patients remained free of clinical T1D versus 22% in the placebo group. In patients treated with teplizumab, the median time to develop clinical T1D was delayed by 25 months.
- The most common adverse events in patients treated with teplizumab were low white blood cell counts, rash, and headache.
- Tzield is the first disease-modifying agent approved for patients with T1D. Insulin is the backbone treatment for T1D, with rapid-acting analogs and long-acting insulin analogs typically recommended versus regular human insulin. Some analogs may be used in insulin pumps. Symlin® (pramlintide acetate pen injection – Astra Zeneca), a synthetic analog of amylin, is the only non-insulin medication approved for T1D. Patients also need to control glucose levels with finger stick monitoring or continuous glucose monitoring (CGM), diet, and exercise. An “artificial pancreas” or “closed loop system” are terms used to describe insulin pumps when combined with CGM to control T1D.
- Tzield was approved as an Orphan Drug and Breakthrough Therapy.