On November 17, 2022, the FDA announced the approval of TZIELDTM (teplizumab-mzwv), which is a CD-3 directed monoclonal antibody. This first-in-class therapy is intended to delay the onset of stage 3 type 1 diabetes (T1D) in individuals 8 years and older with stage 2 T1D. Stage 2 T1D is defined as at least two positive pancreatic islet autoantibodies and dysglycemia, but not overt hyperglycemia, on an OGTT. Stage T1D must be confirmed prior to initiating treatment with TZIELD (1).
The approval was based on data from a phase 2, randomized, placebo-controlled, double-blind international trial, which included 76 participants 8 years and older who were at high risk of developing clinical diabetes (2), as well as data from an extension of that trial (3). The median times to diagnosis of clinical diabetes was 59.6 months in the teplizumab group and 27.1 months in placebo group with a hazard ratio of 0.457 (teplizumab vs. placebo) (3). At a median of 923 days, 50% of teplizumab-treated participants had been diagnosed with clinical diabetes compared to 78% of placebo-treated participants (3). The study also found that teplizumab reversed a decline in insulin secretion seen prior to therapy and stabilized the c-peptide area under the curve (3). Prespecified subgroup analyses in the original study found that the presence of HLA-DR4 and absence of HLA-DR3 and ZnT8 autoantibodies were associated with better response to teplizumab (2). Limitations of the study included that the cohort was predominantly non-Hispanic white (2).
Teplizumab is given via intravenous infusion over at least 30 minutes once daily for 14 days. It must be diluted in 0.9% sodium chloride as per manufacturer instructions. Patients should be premedicated with 1) an NSAID or acetaminophen, 2) an antihistamine, and/or 3) an antiemetic before each teplizumab dose for at least the first 5 days of the 14-day therapy (1).
Teplizumab dosing schedule:
Day 1: 65 mcg/m2
Day 2: 125 mcg/m2
Day 3: 250 mcg/m2
Day 4: 500 mcg/m2
Day 5-14: 1030 mcg/m2
Complete blood counts and liver enzymes should be monitored prior to and during teplizumab therapy (1). The most common adverse reactions were lymphopenia, rash, leukopenia, and headache (1). Additionally, there is risk for cytokine release syndrome (characterized by at least some of the following: fever, nausea, fatigue, headache, myalgia, arthralgia, increased ALT, increased AST, and/or increased total bilirubin) and hypersensitivity reactions. Teplizumab should NOT be used in patients with active serious or chronic infections (1). All age-appropriate vaccinations should be given prior to teplizumab therapy with live-attenuated vaccines given at least 8 weeks before or 52 weeks after therapy and inactivated or mRNA vaccines given at least 2 weeks before or 6 weeks after therapy (1).
- TZIELDTM (teplizumab-mzwv) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761183s000lbl.pdf Revised 11/2022. Accessed 11/17/2022.
- Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ, Type 1 Diabetes TrialNet Study G. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. The New England journal of medicine. 2019;381(7):603-13. Epub 2019/06/11. doi: 10.1056/NEJMoa1902226. PubMed PMID: 31180194; PMCID: PMC6776880.
- Sims EK, Bundy BN, Stier K, Serti E, Lim N, Long SA, Geyer SM, Moran A, Greenbaum CJ, Evans-Molina C, Herold KC, Type 1 Diabetes TrialNet Study G. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med. 2021;13(583). Epub 2021/03/05. doi: 10.1126/scitranslmed.abc8980. PubMed PMID: 33658358; PMCID: PMC8610022.
Prepared on behalf of the PES Drug & Therapeutics committee by Sowmya Krishnan, MD and Laura C. Page, MD.
Last updated: 11/28/22