The Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) for Tzield (teplizumab-mzwv) to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years of age and older who have stage 2 type 1 diabetes.

Tzield is anti-CD3 monoclonal antibody that has been shown to preserve beta cell function, reducing the need for exogenous insulin. The mechanism may involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes, which leads to an increase in the proportion of regulatory T cells and of exhausted CD8+ T cells in peripheral blood.

The approval was based on data from a randomized, double-blind, event-driven, placebo-controlled phase 2 study (Study TN-10; ClinicalTrials.gov Identifier: NCT01030861), which evaluated the efficacy and safety of teplizumab-mzwv in 76 patients 8 to 49 years of age with stage 2 type 1 diabetes. Patients were randomly assigned to receive teplizumab-mzwv once daily via intravenous infusion (n=44) or placebo (n=32) for 14 days. The primary endpoint was the time from randomization to development of stage 3 type 1 diabetes diagnosis.

After a median follow-up time of 51 months, 45% (n=20) of patients treated with teplizumab-mzwv developed stage 3 type 1 diabetes compared with 72% (n=23) of patients treated with placebo. The median time from randomization to stage 3 type 1 diabetes diagnosis was 50 months in the teplizumab-mzwv arm and 25 months in the placebo arm (difference of 25 months). Treatment with teplizumab-mzwv demonstrated a statistically significant delay in the development of stage 3 type 1 diabetes (hazard ratio, 0.41; 95% CI, 0.22-0.78; P =.0066).

The most common adverse reactions reported with Tzield were lymphopenia, rash, leukopenia, and headache. In clinical trials, cytokine release syndrome and serious infections were observed in Tzield-treated patients.

“Today’s approval of a first-in-class therapy adds an important new treatment option for certain at-risk patients,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “The drug’s potential to delay clinical diagnosis of type 1 diabetes may provide patients with months to years without the burdens of disease.”

Tzield is supplied as a 2mg/2mL solution in single-dose vials. Treatment is administered by intravenous infusion once daily for 14 consecutive days.

References

1. FDA approves first drug that can delay onset of type 1 diabetes. News release. US Food and Drug Administration. November 17, 2022. Accessed November 18, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-can-delay-onset-type-1-diabetes.
2. Tzield™ (teplizumab-mzwv) approved by FDA as the first and only treatment indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients aged 8 years and older with Stage 2 T1D. News release. Provention Bio, Inc. November 17, 2022. Accessed November 18, 2022. https://www.prnewswire.com/news-releases/tzield-teplizumab-mzwv-approved-by-fda-as-the-first-and-only-treatment-indicated-to-delay-the-onset-of-stage-3-type-1-diabetes-t1d-in-adult-and-pediatric-patients-aged-8-years-and-older-with-stage-2-t1d-301682218.html.
3. Tzield. Package Insert. Provention Bio, Inc.; 2022. Accessed November 18, 2022.  https://static1.squarespace.com/static/5f4574ed93f3456c76f3a95d/t/6376c9452abcde44dd5d8ae5/1668729158250/tzield-prescribing-information-and-medication-guide.pdf.