Drug Update · Endocrinology

FDA Expands Tzield (teplizumab) Label to Stage 2 T1D ≥1 Year; TN-10 Shows HR 0.41 to Stage 3

September 06, 2026

Supplemental approval date

2026-06-12

Label effective date

2026-08-14

Study TN-10 HR

HR 0.41 (95% CI 0.22-0.78)

TN-10 median time to Stage 3

50 months (TZIELD) vs 25 months (placebo)

PROTECT enrollment

328 patients aged 8 to 17 years

Clinical Perspective

This affects healthcare professionals evaluating and treating patients with Stage 2 T1D (adult and pediatric patients 1 year and older) and pediatric patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. The labeling update supports use of TZIELD to delay progression to Stage 3 T1D and to delay decline in endogenous insulin production in the specified pediatric population based on the trial and surrogate C-peptide evidence cited in the approval. Will the ongoing confirmatory/postapproval study verify a durable clinical benefit that supports continued approval?

Dr. Amit Desai, MBBS, MD (General Medicine), DM (Endocrinology) · Endocrinology

Tzield (teplizumab-mzwv) labeling was updated in mid-2026 to include use to delay onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients 1 year of age and older with Stage 2 T1D, and to delay decline in endogenous insulin production in pediatric patients aged 8 to 17 years with recently diagnosed Stage 3 T1D. The labeling change follows FDA regulatory action with a supplemental approval date of 2026-06-12 and supporting trial evidence including Study TN-10 showing prolonged time to Stage 3 diagnosis (HR 0.41; 95% CI 0.22-0.78) ^[3]^[1]^[2].

Clinical Context

Tzield (teplizumab-mzwv, a CD3-directed monoclonal antibody) is manufactured and marketed with prescribing information posted on DailyMed and the FDA label database. The approved indications now include delaying the onset of Stage 3 T1D in adult and pediatric patients 1 year and older with Stage 2 T1D and delaying decline in endogenous insulin production in pediatric patients aged 8 to 17 years with recent Stage 3 T1D; the Stage 3 pediatric approval was granted under the FDA's accelerated approval pathway on June 12, 2026 ^[1]^[2]^[3]. The product label contains extensive patient-selection criteria, laboratory and infection evaluation requirements, and monitoring recommendations tied to known risks including viral reactivation and lymphopenia ^[1]^[3].

Key Findings

In the randomized, double-blind, event-driven, placebo-controlled Study TN-10 (patients 8 to 49 years with Stage 2 T1D), TZIELD reduced the risk of progression to Stage 3 T1D versus placebo (HR 0.41; 95% CI 0.22-0.78). With median follow-up of 51 months, Stage 3 T1D occurred in 20/44 (45%) TZIELD-treated patients versus 23/32 (72%) placebo-treated patients, and median time to Stage 3 diagnosis was 50 months with TZIELD versus 25 months with placebo ^[3].
The FDA granted accelerated approval for the Stage 3 pediatric indication based on evidence of a statistically significant effect on C-peptide (a surrogate endpoint reasonably likely to predict clinical benefit); a required postapproval study is ongoing to verify clinical benefit ^[2]^[3].
The approved labeling specifies patient selection criteria for Stage 2: confirmation of at least two positive pancreatic islet cell autoantibodies and dysglycemia without overt hyperglycemia by OGTT or alternative method, and for Stage 3 pediatric use: at least one positive pancreatic islet cell autoantibody and peak C-peptide ≥0.2 pmol/mL on a MMTT or alternative method ^[1]^[3].
The prescribing information includes BSA-based dosing schedules and infusion-duration requirements tied to age groups and provides detailed recommendations on premedication and laboratory evaluation prior to initiation ^[1]^[3].

Safety & Tolerability

Boxed Warning: Viral reactivation, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation, has been reported with TZIELD; TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV) and patients should be tested for active EBV and CMV prior to treatment ^[1]^[3].
Warnings and precautions in the label include cytokine release syndrome (CRS), serious infections, lymphopenia (including criteria for discontinuation), hypersensitivity reactions, and vaccination timing recommendations ^[1]^[3].
Most common adverse reactions listed in the label are lymphopenia, vomiting, rash, leukopenia, diarrhea, neutropenia, increased liver transaminase, and headache ^[1]^[3].

Study Design

Study TN-10 was a randomized, double-blind, event-driven, placebo-controlled study in 76 patients 8 to 49 years of age with Stage 2 T1D; patients were randomized to receive TZIELD or placebo once daily by intravenous infusion for 14 days and the primary efficacy endpoint was time from randomization to development of Stage 3 T1D (median follow-up 51 months) ^[3]. Clinicians should consult current prescribing information for full dosing guidance. The PROTECT Study was a randomized, double-blind, placebo-controlled, multinational, multicenter study (328 patients aged 8 to 17 years recently diagnosed with Stage 3 T1D) with the primary efficacy endpoint defined as change from baseline in stimulated C-peptide at Week 78; the FDA granted accelerated approval for the Stage 3 pediatric indication based on a statistically significant effect on C-peptide and a postapproval study is ongoing ^[3]^[2]. The most recent supplemental approval date is 2026-06-12 and the label revision effective date is 2026-08-14 ^[3]^[1].

FAQ

Q1 What is Tzield (Tzield) approved for?

Tzield (teplizumab-mzwv) is indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients 1 year of age and older with Stage 2 T1D, and to delay the decline in endogenous insulin production in pediatric patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. The Stage 3 pediatric indication was approved under the accelerated approval pathway and continued approval may depend on verification of clinical benefit in postapproval studies.

Q2 How does teplizumab work?

Teplizumab-mzwv is a CD3-directed antibody that binds to CD3 on T lymphocytes and may deactivate pancreatic beta cell autoreactive T lymphocytes; the mechanism may involve partial agonistic signaling, an increase in regulatory T cells, and an increase in exhausted CD8+ T cells in peripheral blood, which is postulated to delay beta cell destruction and preserve endogenous insulin production.

Q3 What is the recommended dose of Tzield?

For Stage 2 T1D the approved regimen is administered once daily by intravenous infusion for 14 consecutive days using body-surface-area (BSA)-based dosing with the following daily dosages: 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; infuse over a minimum of 30 minutes in adults and pediatric patients aged 8 years and older and over 2 hours in pediatric patients aged 1 to less than 8 years. For Stage 3 pediatric use the regimen is administered once daily for 12 days (with additional dosing schedules described in the full prescribing information). Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of Tzield?

The most common adverse reactions listed in the prescribing information are lymphopenia, vomiting, rash, leukopenia, diarrhea, neutropenia, increased liver transaminase, and headache. The label includes a boxed warning for viral reactivation (EBV and CMV) and specifies contraindications, monitoring requirements for lymphocyte counts and liver enzymes, and guidance on vaccinations and infection evaluation prior to initiation.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Expands Tzield (teplizumab) Label to Stage 2 T1D ≥1 Year; TN-10 Shows HR 0.41 to Stage 3

Direct Clinical Takeaway & Evidence Summary

FDA Expands Tzield (teplizumab) Label to Stage 2 T1D ≥1 Year; TN-10 Shows HR 0.41 to Stage 3

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Cite & Reference This Monograph

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